Search

The β-glucosidase gene from Aspergillus nidulans FGSC A4 was cloned and overexpressed in the A. nidulans A773. The resulting purified β-glucosidase, named AnGH3, is a monomeric enzyme with a molecular weight of approximately 80 kDa, as confirmed by SDS-PAGE. Circular dichroism further validated its unique canonical barrel fold (β/α), a feature also observed in the 3D homology model of AnGH3. The most striking aspect of this recombinant enzyme is its robustness, as it retained 100% activity after 24 h of incubation at 45 and 50 ºC and pH 6.0. Even at 55 °C, it maintained 72% of its enzymatic activity after 6 h of incubation at the same pH. The kinetic parameters Vmax, KM, and Kcat/KM for ρ-nitrophenyl-β-D-glucopyranoside (ρNPG) and cellobiose were also determined. Using ρNPG, the enzyme demonstrated a Vmax of 212 U mg − 1, KM of 0.0607 mmol L − 1, and Kcat/KM of 4521 mmol L − 1 s − 1 when incubated at pH 6.0 and 65 °C. The KM, Vmax, and Kcat/KM using cellobiose were 2.7 mmol L − 1, 57 U mg − 1, and 27 mmol –1 s − 1, respectively. AnGH3 activity was significantly enhanced by xylose and ethanol at concentrations up to 1.5 mol L − 1 and 25%, respectively. Even in challenging conditions, at 65 °C and pH 6.0, the enzyme maintained its activity, retaining 100% and 70% of its initial activity in the presence of 200 mmol L − 1 furfural and 5-hydroxymethylfurfural (HMF), respectively. The potential of this enzyme was further demonstrated by its application in the saccharification of the forage grass Panicum maximum, where it led to a 48% increase in glucose release after 24 h. These unique characteristics, including high catalytic performance, good thermal stability in hydrolysis temperature, and tolerance to elevated concentrations of ethanol, D-xylose, furfural, and HMF, position this recombinant enzyme as a promising tool in the hydrolysis of lignocellulosic biomass as part of an efficient multi-enzyme cocktail, thereby opening new avenues in the field of biotechnology and enzymology. [ABSTRACT FROM AUTHOR]

Biological macromolecules are found in different shapes and sizes. Among these, enzymes catalyze biochemical reactions and are essential in all organisms, but is there a limit size for them to function properly? Large enzymes such as catalases have hundreds of kDa and are formed by multiple subunits, whereas most enzymes are smaller, with molecular weights of 20–60 kDa. Enzymes smaller than 10 kDa could be called microenzymes and the present literature review brings together evidence of their occurrence in nature. Additionally, bioactive peptides could be a natural source for novel microenzymes hidden in larger peptides and molecular downsizing could be useful to engineer artificial enzymes with low molecular weight improving their stability and heterologous expression. An integrative approach is crucial to discover and determine the amino acid sequences of novel microenzymes, together with their genomic identification and their biochemical biological and evolutionary functions. [ABSTRACT FROM AUTHOR]

The endo-1,4-β-xylanases (EC 3.2.1.8) are the largest group of hydrolytic enzymes that degrade xylan, the major component of hemicelluloses, by catalyzing the hydrolysis of glycosidic bonds β-1,4 in this polymer, releasing xylooligosaccharides of different sizes. Xylanases have considerable potential in producing bread, animal feed, food, beverages, xylitol, and bioethanol. The fungus Aspergillus tamarii Kita produced xylanases in Adams' media supplemented with barley bagasse (brewer's spent grains), a by-product from brewery industries. The culture extract exhibited two xylanase activities in the zymogram, identified by mass spectrometry as glycosyl hydrolase (GH) families 10 and 11 (GH 10 and GH 11). The central composite design (CCD) showed excellent predictive capacity for xylanase production (23.083 U mL−1). Additionally, other enzyme activities took place during the submerged fermentation. Moreover, enzymatic saccharification based on a mixture design (MD) of three different lignocellulosic residues was helpful in the production of fermentable sugars by the A. tamarii Kita crude extract. [ABSTRACT FROM AUTHOR]

Dementia, a global health priority, poses a disproportionately high risk to lesbian, gay, bisexual and trans plus (LGBT+)/gender and sexuality diverse people. Despite this, little research has explored the lived experience of LGBT+ people with dementia or their care partners. This scoping review aims to understand what the literature reveals about their experiences, the ways in which their lives have been investigated, to inform future research, policy and practice. Using an established scoping review methodology, we identified seven papers that reported empirical research on the lived experience of LGBT+ people with dementia and their care partners. Only a single study reported on in two of the papers included people who were trans. This in itself reveals how rarely LGBT+ people are asked to speak about how dementia has shaped their lives in academic research. Our reflexive thematic analysis indicates that LGBT+ people with dementia and their care partners endure overlapping forms of disadvantage. This results in heightened experiences of fear and discrimination, lack of services and compounded social isolation. Importantly, while dementia was embodied as interference and loss by LGBT+ people, it was their gender and sexuality differences that provided solace, even in the face of disadvantage. Importantly, people's relationships with LGBT+ identities were framed as fundamental for safety, resilience and wellbeing, rather than a complicating or confounding factor in living with dementia. [ABSTRACT FROM AUTHOR]

Primary cell walls and middle lamella of higher plants include homogalacturonan, the substrate for polygalacturonases. Seeking to enhance lignocellulose saccharification, chimeras between the endopolygalacturonase I from Chondrostereum (Stereum) purpureum (EndoPG-I) and family 3, 44, and 77 carbohydrate-binding modules (CBMs) from Hungateiclostridium thermocellum (Ht) or Ruminococcus flavefaciens (Rf) were constructed, expressed, and characterized. Chimeras presented similar KM values and pH/temperature optima as unfused EndoPG-I against citrus pectin, kcat/KM values 1.6, 1.7, and 1.3-fold higher for the HtCBM3-EndoPG, HtCBM44-EndoPG, and RtCBM77-EndoPG, respectively. Commercial enzyme cocktail supplementation with HtCBM44-EndoPG and RtCBM77-EndoPG increased reducing sugar release from untreated sugarcane bagasse by 35 and 25%, respectively. All chimeras increased reducing sugar release by 20–25% against orange bagasse compared with EndoPG-I or equimolar EndoPG-I/CBM mixtures. These results show that proximity between plant cell wall components in situ influences CBM-enzyme chimera activity and improves saccharification of lignocellulosic materials. [ABSTRACT FROM AUTHOR]

Xylanases are of significant interest for biomass conversion technologies. Here, we investigated the allosteric regulation of xylan hydrolysis by the Bacillus subtilis GH11 endoxylanase. Molecular dynamics simulations (MDS) in the presence of xylobiose identified binding to the active site and two potential secondary binding sites (SBS) around surface residues Asn54 and Asn151. Arabinoxylan titration experiments with single cysteine mutants N54C and N151C labeled with the thiol‐reactive fluorophore acrylodan or the ESR spin‐label MTSSL validated the MDS results. Ligand binding at the SBS around Asn54 confirms previous reports, and analysis of the second SBS around N151C discovered in the present study includes residues Val98/Ala192/Ser155/His156. Understanding the regulation of xylanases contributes to efforts for industrial decarbonization and to establishing a sustainable energy matrix. [ABSTRACT FROM AUTHOR]

Background: Recent findings suggest that the plasma axonal structural protein, neurofilament light (NFL) chain, may serve as a potential blood biomarker for early signs of neurodegenerative diseases, such as Alzheimer's disease (AD). Given the need for early detection of neurodegenerative disorders, the current study investigated the associations between regional cerebral blood flow (rCBF) in brain regions associated with neurodegenerative disorders and memory function with plasma NFL in AD, mild cognitive impairment (MCI), and healthy controls (HCs). Methods: We recruited 29 AD, 76 MCI, and 39 HCs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database in the current cross-sectional study. We used Pearson's correlation models adjusted for the effect of age, sex, and APOE genotype to investigate the association between plasma NFL and rCBF. Results: We found non-significant differences in age (F(2, 141) = 1.304; P = 0.275) and years of education (F(2, 141) = 0.013; P = 0.987). Additionally, we found significant differences between groups in terms of MMSE scores (F(2, 141) = 100.953; P < 0.001). Despite the observation of significantly reduced rCBF in AD and MCI groups versus HCs, we did not detect significant differences in plasma NFL between these groups. We found significant negative associations between plasma NFL and rCBF in various AD-related regions, these findings were only observed after analyses in all participants, and were observed in HCs alone and no significant associations were observed in the AD or MCI groups. Conclusion: These outcomes add to our current understanding surrounding the use of rCBF and plasma NFL biomarkers as tools for early detection and diagnosis of neurodegenerative diseases. A conclusion might be that the association between NFL and impaired rCBF exists before the clinical symptoms appear. Further longitudinal studies with a large sample size should be performed to examine the correlation between plasma NFL and rCBF in order to understand these complex relationships. [ABSTRACT FROM AUTHOR]

Tomato brown rugose fruit virus (ToBRFV) is a contact-transmitted tobamovirus affecting many tomato growing regions of the world. This study investigated the effects of different glasshouse surfaces on the survival of the virus; the efficacy of different disinfectants; and heat treatment against ToBRFV (surfaces included steel, aluminium, hard plastic, polythene, glass and concrete). A bioassay followed by ELISA was used to check virus viability. ToBRFV survived for at least 7 days on all surfaces tested and on some for at least 6 months. The virus survived for over two hours on hands and gloves. Hand washing was shown to be unreliable for the removal of the virus. Glutaraldehyde and quaternary ammonium compound disinfectants were effective at one hour on all surfaces. Some other disinfectants were effective at one hour of contact time, on all surfaces except concrete. Sodium hypochlorite was partially effective against ToBRFV, even on concrete. A 5 min soak of plastic trays in water at 90 °C was effective at denaturing ToBRFV; however, 5 min at 70 °C was not. Heating infected sap showed the thermal inactivation point to be 90 °C, confirming the hot water treatment results and showing that deactivation was due to the heat treatment and not a washing effect of the water. [ABSTRACT FROM AUTHOR]

Objectives: This paper considers home from the perspective of people living with dementia supporting ongoing discourse around ageing in place and the significance of creating more inclusive communities. Methods: Forty‐six home tour interviews led by people living with dementia were conducted in England and Scotland to better understand the connectivity between home and neighbourhood for people living with dementia. These interviews used a range of participatory and creative approaches including video, photographic images and in situ interviews. Data were analysed via reflexive thematic analysis. Results: Three themes were identified in data analysis. 1. Connected home and neighbourhood, where participants revealed the dynamic relationship between home and neighbourhood; 2. Practices of home, where participants discussed the everyday nature of their homes and routines; and 3. Displaying home and family, which reflected participant's biographical homes in the context of living with dementia. Discussion: The findings show that home holds multiple meanings for people living with dementia. For example, home is understood as a part of the neighbourhood and an extension of the home space into gardens and backyards, thus extending existing discourses that solely focus on the inside of people's homes. For people living with dementia, homes are also sites of negotiation and renegotiation where new meanings are created to reflect the changing nature and context of the home. There is not one fixed solution to these issues. Support and understanding for people living with dementia will need to evolve to adapt to the shifting dynamics and multiple meanings of home. Key points: Neighbourhoods begin within homes and are interconnected. This relationship has important implications for the discourse of ageing in place.'Home' for people living with dementia holds the same meanings for those without dementia, but with some notable differences. It is important to recognise the shifting dynamics of home and to recognise the complexity of home in the context of dementia. There is not a fixed solution to the challenges of ageing at home with dementia, but support and understanding need to evolve alongside people with lived experience.Homes are a site of renegotiation where new meanings are created to reflect the changing nature of home and the lived experience of home for those with dementia.The study has provided findings through innovation in the research design. The employment of creative methods enabled people living with dementia to participate in sharing their own narratives of home.The work provides evidence where there is a current gap in understanding 'what matters' about home for people living with dementia. [ABSTRACT FROM AUTHOR]

BACKGROUND: Sickle cell disease (SCD) is a genetic disorder characterized by hemolytic anemia and vaso-occlusive episodes. Many adults with SCD require hospitalization for the management of acute manifestations. There appears to be a gap in the level of knowledge that general internal medicine (GIM) trainees possess regarding the treatment and management of SCD. METHODS: We created an online module that helps medical residents improve their knowledge about SCD. Participants were exposed to different scenarios related to SCD. A pre-and posttests were administered to detect improvement in knowledge and comfort when managing SCD and its acute complications. RESULTS: Thirty consecutive GIM residents participated. Of these, 20 completed the demographic survey, 17 completed the pretest, and 10 completed the posttest and usability survey. The median time to complete the module was 68 min. Fifty percent of participants were 1st-year postgraduation from medical school. Forty-five percent stated that they were uncomfortable managing patients with SCD 80% had cared for at least 1-5 patients with SCD. All reported having no SCD lectures in residency. The median pretest score was 12/20 (range, 8-15) and posttest score was 20.5/25 (range, 13-24). CONCLUSIONS: Residents agreed that the module was useful, helps understanding about SCD and its complication, and aids with clinical duties. This module demonstrated to be an effective educational tool that can support resident education during their internal medicine. Further strategies will be needed to improve the delivery of online modules to keep residents engaged with the module and attaint full benefit from these activities. [ABSTRACT FROM AUTHOR]

Between the first recorded execution at Tyburn in 1196 and the abolition of public executions in 1868, tens of thousands of offenders were publicly executed in London. In Section 6, for example, there was no discussion of the extent to which debates about punishment in the nineteenth century were divided along political lines, and in particular that the abolition of public executions in 1868 was at least in part a move by those who wanted to retain capital punishment as a whole. Some of the research represents genuinely original contributions to our historical knowledge of public execution in London, such as the exhibition's exhaustive identification of past execution sites. [Extracted from the article]

Endoglucanases (EC 3.2.1.4) are important enzymes involved in the hydrolysis of cellulose, acting randomly in the β-1,4-glycosidic bonds present in the amorphous regions of the polysaccharide chain. These biocatalysts have been classified into 14 glycosyl hydrolase (GH) families. The GH7 family is of particular interest since it may act on a broad range of substrates, including cellulose, β-glucan, and xylan, an attractive feature for biotechnological applications, especially in the renewable energy field. In the current work, a gene from the thermophilic fungus Thermothielavioides terrestris, encoding an endoglucanase GH7 (TtCel7B), was cloned in the secretion vector pEXPYR and transformed into the high-protein-producing strain Aspergillus nidulans A773. Purified TtCel7B has a molecular weight of approximately 66 kDa, evidenced by SDS-PAGE. Circular dichroism confirmed the high β-strand content consistent with the canonical GH7 family β-jellyroll fold, also observed in the 3D homology model of TtCel7B. Biochemical characterization assays showed that TtCel7B was active over a wide range of pH values (3.5–7.0) and temperatures (45–70 °C), with the highest activity at pH 4.0 and 65 °C. TtCel7B also was stable over a wide range of pH values (3.5–9.0), maintaining more than 80% of its activity after 24 h. The KM and Vmax values in low-viscosity carboxymethylcellulose were 9.3 mg mL−1 and 2.5 × 104 U mg−1, respectively. The results obtained in this work provide a basis for the development of applications of recombinant TtCel7B in the renewable energy field. [ABSTRACT FROM AUTHOR]

'Dementia-friendly communities' herald a shift toward the neighbourhood as a locus for the care and support of people with dementia, sparking growing interest in the geographies of dementia care and raising questions over the shifting spatial and social experience of the condition. Existing research claims that many people with dementia experience a 'shrinking world' whereby the boundaries to their social and physical worlds gradually constrict over time, leading to a loss of control and independence. This paper reports a five-year, international study that investigated the neighbourhood experience of people with dementia and those who care for and support them. We interrogate the notion of a shrinking world and in so doing highlight an absence of attention paid to the agency and actions of people with dementia themselves. The paper draws together a socio-relational and embodied-material approach to question the adequacy of the shrinking world concept as an explanatory framework and to challenge reliance within policy and practice upon notions of place as fixed or stable. We argue instead for the importance of foregrounding 'lived place' and attending to social practices and the networks in which such practices evolve. Our findings have implications for policy and practice, emphasising the need to bolster the agency of people living with dementia as a route to fostering accessible and inclusive neighbourhoods. [ABSTRACT FROM AUTHOR]

Xyloglucan (XG) is an abundant polysaccharide in plant cell walls and some seeds and requires at least four different enzymes for complete depolymerization. Recombinant xyloglucanase from Aspergillus niveus (XegA), α‐xylosidase from Escherichia coli (YicI), β‐galactosidase from Hypocrea jecorina (Bga1) and β‐glucosidase from H. jecorina (Bgl1) were covalently immobilized individually and in combination on chitosan‐coated ferromagnetic iron oxide nanoparticles functionalized with glutaraldehyde. All immobilized enzymes presented reduced specific catalytic activity, where immobilized YicI, XegA, Bga1 and Bgl1 retained 14.9, 76.9, 29.5 and 6.6% activity as compared with the free enzymes, respectively. Immobilized and free enzymes presented similar optimum catalytic pH and optimum catalytic temperatures differed by ±10°C between the free and immobilized enzymes. Bga1 and Bgl1 presented decreased maximum catalytic temperatures (Topt), while YicI presented an increased Topt. The Topt of XegA remained unaltered. Mass spectrometry confirmed that nanoparticles carrying all four co‐immobilized enzymes degraded XG to glucose, galactose and xylose, and higher proportions of co‐immobilized Bgl1 and XegA resulted in higher XG saccharification. Although levels of Bgl1 activity were limiting, five re‐use cycles of the co‐immobilized enzymes were demonstrated, providing proof‐of‐principle for the use of a four‐component multienzyme nanoparticle in the breakdown of a complex polysaccharide. © 2022 Society of Chemical Industry and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Dementia is a global health challenge and currently the focus of a coordinated international response articulated through the notion of 'dementia‐friendly communities and initiatives' (DFCIs). Yet, while increasing research attention has been paid to the social and spatial dimensions to life with dementia in a neighbourhood setting, the temporalities of dementia have been largely overlooked. This article sets out different aspects of the lived experience of time for people with dementia and unpaid carers, before exploring the temporal politics of formal dementia care and support. The authors show that time is a site for material struggle and a marker of unequal relations of power. People with dementia and unpaid carers are disempowered through access to formal care, and this is illustrated in their loss of (temporal) autonomy and limited options for changing the conditions of the care received. The authors advocate for a time‐space configured understanding of the relationship with neighbourhood and foreground a tempo‐material understanding of dementia. Set against the backdrop of austerity policy in the UK, the findings reveal that ongoing budgetary restrictions have diminished the capacity for social care to mediate in questions of social justice and inequality, at times even compounding inequity. [ABSTRACT FROM AUTHOR]

In today's society, we are constantly absorbing information via text (e.g., news, social media), much of which may be affectively charged. However, to date, little is known about how the affective framing of the text itself may give rise to various affective experiences during reading. We examined how subtle changes to wording (negatively or positively valenced framing of the same content) influenced affective experiences during reading and subsequent comprehension. Results show that (a) affective framing in text elicited congruent subjective affective states throughout reading, (b) subjective affective valence throughout reading impacted comprehension at various levels, and (c) subjective affective valence mediated the relationship between affective framing and how participants integrated information from the text in their summaries, as well as if they included affect in their summaries. This indicates that even subtle affectively valenced content in text can indirectly influence some aspects of comprehension through eliciting subjective affective experiences in the reader. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with dementia and is a serious concern for the health of individuals and government health care systems worldwide. Gray matter atrophy and white matter damage are major contributors to cognitive deficits in AD patients, as demonstrated by magnetic resonance imaging (MRI). Many of these brain changes associated with AD begin to occur about 15 years before the onset of initial clinical symptoms. Therefore, it is critical to find biomarkers reflective of these brain changes associated with AD to identify this disease and monitor its prognosis and development. The increased plasma level of hyperphosphorylated tau 181 (p-tau181) has been recently considered a novel biomarker for the diagnosis of AD, preclinical AD, and mild cognitive impairment (MCI). In the current study, we examined the association of cerebrospinal fluid (CSF) and plasma levels of p-tau181 with structural brain changes in cortical thickness, cortical volume, surface area, and subcortical volume in MCI patients. In this cross-sectional study, we included the information of 461 MCI patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. The results of voxel-wise partial correlation analyses showed a significant negative correlation between the increased levels of plasma p-tau181, CSF total tau, and CSF p-tau181 with structural changes in widespread brain regions. These results provide evidence for the use of plasma p-tau181 as a diagnostic marker for structural changes in the brain associated with the early stages of AD and neurodegeneration. [ABSTRACT FROM AUTHOR]

Approximately 20% of individuals who experience a traumatic injury will subsequently develop posttraumatic stress disorder (PTSD). Physical pain following traumatic injury has received increasing attention as both a distinct, functionally debilitating disorder and a comorbid symptom related to PTSD. Studies have demonstrated that both clinician‐assessed injury severity and patient pain ratings can be important predictors of nonremitting PTSD; however, few have examined pain and PTSD alongside socioenvironmental factors. We postulated that both area‐ and individual‐level socioeconomic circumstances and lifetime trauma history would be uniquely associated with PTSD symptoms and interact with the pain–PTSD association. To test these effects, pain and PTSD symptoms were assessed at four visits across a 1‐year period in a sample of 219 traumatically injured participants recruited from a Level 1 trauma center. We used a hierarchal linear modeling approach to evaluate whether (a) patient‐reported pain ratings were a better predictor of PTSD than clinician‐assessed injury severity scores and (b) socioenvironmental factors, specifically neighborhood socioeconomic disadvantage, individual income, and lifetime trauma history, influenced the pain–PTSD association. Results demonstrated associations between patient‐reported pain ratings, but not clinician‐assessed injury severity scores, and PTSD symptoms, R2(fvm) =.65. There was a significant interaction between neighborhood socioeconomic disadvantage and pain such that higher disadvantage decreased the strength of the pain–PTSD association but only among White participants, R2(fvm) =.69. Future directions include testing this question in a larger, more diverse sample of trauma survivors (e.g., geographically diverse) and examining factors that may alleviate both pain and PTSD symptoms. [ABSTRACT FROM AUTHOR]

The serotonergic system extends throughout the central nervous system (CNS) and the gastrointestinal (GI) tract. In the CNS, serotonin (5-HT, 5-hydroxytryptamine) modulates a broad spectrum of functions, including mood, cognition, anxiety, learning, memory, reward processing, and sleep. These processes are mediated through 5-HT binding to 5-HT receptors (5-HTRs), are classified into seven distinct groups. Deficits in the serotonergic system can result in various pathological conditions, particularly depression, schizophrenia, mood disorders, and autism. In this review, we outlined the complexity of serotonergic modulation of physiologic and pathologic processes. Moreover, we provided experimental and clinical evidence of 5-HT's involvement in neuropsychiatric disorders and discussed the molecular mechanisms that underlie these illnesses and contribute to the new therapies. [ABSTRACT FROM AUTHOR]

Misophonia is characterized by excessive aversive reactions to specific "trigger" sounds. Although this disorder is increasingly recognized in the literature, its etiological mechanisms and maintaining factors are currently unclear. Several etiological models propose a role of Pavlovian conditioning, an associative learning process heavily researched in similar fear and anxiety-related disorders. In addition, generalization of learned associations has been noted as a potential causal or contributory factor. Building upon this framework, we hypothesized that Misophonia symptoms arise as a consequence of overgeneralized associative learning, in which aversive responses to a noxious event also occur in response to similar events. Alternatively, heightened discrimination between conditioned threat and safety cues may be present in participants high in Misophonia symptoms, as predicted by associative learning models of Misophonia. This preliminary report (n = 34) examines auditory generalization learning using self-reported behavioral (i.e., valence and arousal ratings) and EEG alpha power reduction. Participants listened to three sine tones differing in pitch, with one pitch (i.e., CS+) paired with an aversive loud white noise blast, prompting aversive Pavlovian generalization learning. We assessed the extent to which overgeneralization versus heightened discrimination learning is associated with self-reported Misophonia symptoms, by comparing aversive responses to the CS+ and other tones similar in pitch. Behaviorally, all participants learned the contingencies between CS+ and noxious noise, with individuals endorsing elevated Misophonia showing heightened aversive sensitivity to all stimuli, regardless of conditioning and independent of hyperacusis status. Across participants, parieto-occipital EEG alpha-band power reduction was most pronounced in response to the CS+ tone, and this difference was greater in those with self-reported Misophonia symptoms. The current preliminary findings do not support the notion that overgeneralization is a feature of self-reported emotional experience in Misophonia, but that heightened sensitivity and discrimination learning may be present at the neural level. [ABSTRACT FROM AUTHOR]

The quaternary organization of rhodopsin-like G protein-coupled receptors in native tissues is unknown. To address this we generated mice in which the M1 muscarinic acetylcholine receptor was replaced with a C-terminally monomeric enhanced green fluorescent protein (mEGFP)-linked variant. Fluorescence imaging of brain slices demonstrated appropriate regional distribution, and using both anti-M1 and anti-green fluorescent protein antisera the expressed transgene was detected in both cortex and hippocampus only as the full-length polypeptide. M1-mEGFP was expressed at levels equal to the M1 receptor in wild-type mice and was expressed throughout cell bodies and projections in cultured neurons from these animals. Signaling and behavioral studies demonstrated M1-mEGFP was fully active. Application of fluorescence intensity fluctuation spectrometry to regions of interest within M1-mEGFP-expressing neurons quantified local levels of expression and showed the receptor was present as a mixture of monomers, dimers, and higher-order oligomeric complexes. Treatment with both an agonist and an antagonist ligand promoted monomerization of the M1-mEGFP receptor. The quaternary organization of a class A G protein-coupled receptor in situ was directly quantified in neurons in this study, which answers the much-debated question of the extent and potential ligand-induced regulation of basal quaternary organization of such a receptor in native tissue when present at endogenous expression levels. [ABSTRACT FROM AUTHOR]

Since its beginnings in the early 20th century, the psychophysiological study of human brain function has included research into the spectral properties of electrical and magnetic brain signals. Now, dramatic advances in digital signal processing, biophysics, and computer science have enabled increasingly sophisticated methodology for neural time series analysis. Innovations in hardware and recording techniques have further expanded the range of tools available to researchers interested in measuring, quantifying, modeling, and altering the spectral properties of neural time series. These tools are increasingly used in the field, by a growing number of researchers who vary in their training, background, and research interests. Implementation and reporting standards also vary greatly in the published literature, causing challenges for authors, readers, reviewers, and editors alike. The present report addresses this issue by providing recommendations for the use of these methods, with a focus on foundational aspects of frequency domain and time‐frequency analyses. It also provides publication guidelines, which aim to (1) foster replication and scientific rigor, (2) assist new researchers who wish to enter the field of brain oscillations, and (3) facilitate communication among authors, reviewers, and editors. Dramatic advances in digital signal processing, biophysics, and computer science have produced increasingly sophisticated methods for neural time series analysis. These methods are used by a growing number of researchers who vary in their training, background, and research interests, causing challenges for authors, readers, reviewers, and editors alike. The present report addresses this issue by providing recommendations for the use of these methods, with a focus on foundational aspects of frequency‐domain and time‐frequency analyses. [ABSTRACT FROM AUTHOR]

Friction drilling is a non-conventional hole-making process suitable for thin-section, ductile metals. During friction drilling, heat is generated due to tool rotation and the resulting flow of metal creates a bushing on the exit side of the hole. The bushing offers a longer engagement length for any subsequent thread making process. The threaded holes in this study were created by friction drilling and thread forming in 6082-T6 aluminium alloy. Four scenarios of the threaded holes were created with four levels of rotation rates of friction drilling processes (2000 rpm to 4000 rpm) and the mechanical properties of the threaded holes were compared. It was shown that 3000–3500 rpm is the optimum range of the rotation rate that achieved the higher load-bearing capacities (i.e., resistance to thread stripping) of 5.0–5.5 kN. In addition, the regions close to the thread surfaces in all scenarios were found to have experienced localised hardening to a hardness from 113 HV to around 125 HV. [ABSTRACT FROM AUTHOR]

Pectinases are widely used in a variety of industrial processes. However, their application is limited by low catalytic processivity, reduced stability, high cost, and poor re-use compatibility. These drawbacks may be overcome by enzyme immobilization with ferromagnetic nanoparticles, which are easily recovered by a magnetic field. In this work, an endopolygalacturonase from Chondrostereum purpureum (EndoPGCp) expressed in Pichia pastoris was immobilized on glutaraldehyde-activated chitosan ferromagnetic nanoparticles (EndoPGCp-MNP) and used to supplement a commercial enzyme cocktail. No significant differences in biochemical and kinetic properties were observed between EndoPGCp-MNP and EndoPGCp, although the EndoPGCp-MNP showed slightly increased thermostability. Cocktail supplementation with EndoPGCp-MNP increased reducing sugar release from orange wastes by 1.8-fold and showed a synergistic effect as compared to the free enzyme. Furthermore, EndoPGCp-MNP retained 65% of the initial activity after 7 cycles of re-use. These properties suggest that EndoPGCp-MNP may find applications in the processing of pectin-rich agroindustrial residues. [ABSTRACT FROM AUTHOR]

Previous work suggests that threat-related stimuli are stored to a greater degree in working memory compared to neutral stimuli. However, most of this research has focused on stimuli with physically salient threat attributes (e.g., angry faces), failing to account for how a "neutral" stimulus that has acquired threat-related associations through differential aversive conditioning influences working memory. The current study examined how differentially conditioned safe (i.e., CS–) and threat (i.e., CS+) stimuli are stored in working memory relative to a novel, non-associated (i.e., N) stimuli. Participants (n = 69) completed a differential fear conditioning task followed by a change detection task consisting of three conditions (CS+, CS–, N) across two loads (small, large). Results revealed individuals successfully learned to distinguishing CS+ from CS– conditions during the differential aversive conditioning task. Our working memory outcomes indicated successful load manipulation effects, but no statistically significant differences in accuracy, response time (RT), or Pashler's K measures of working memory capacity between CS+, CS–, or N conditions. However, we observed significantly reduced RT difference scores for the CS+ compared to CS– condition, indicating greater RT differences between the CS+ and N condition vs. the CS– and N condition. These findings suggest that differentially conditioned stimuli have little impact on behavioral outcomes of working memory compared to novel stimuli that had not been associated with previous safe of aversive outcomes, at least in healthy populations. [ABSTRACT FROM AUTHOR]

Objectives: MRI quantification of liver iron concentration (LIC) using R2 or R2* relaxometry requires offline post-processing causing reporting delays, administrative overhead, and added costs. A prototype 3D multi-gradient-echo pulse sequence, with inline post-processing, allows immediate calculation of LIC from an R2* map (inline R2*-LIC) without offline processing. We compared inline R2*-LIC to FerriScan and offline R2* calibration methods. Methods: Forty patients (25 women, 15 men; age 18–82 years), prospectively underwent FerriScan and the prototype sequence, which produces two R2* maps, with and without fat modeling, as well as an inline R2*-LIC map derived from the R2* map with fat modeling, with informed consent. For each map, the following contours were drawn: ROIs, whole-axial-liver contour, and an exact copy of contour utilized by FerriScan. LIC values from the FerriScan report and those calculated using an alternative R2 calibration were the reference standards. Results were compared using Pearson and interclass correlation coefficients (PCC, ICC), linear regression, Bland-Altman analysis, and estimation of area under the receiver operator curve (ROC-AUC). Results: Inline R2*-LIC demonstrated good agreement with the reference standards. Compared to FerriScan, inline R2*-LIC with whole-axial-liver contour, ROIs, and FerriScan contour demonstrated PCC of 94.8%, 94.8%, and 92%; ICC 93%, 92.7%, and 90.2%; regression slopes 1.004, 0.974, and 1.031; mean bias 5.54%, 10.91%, and 0.36%; and ROC-AUC estimates 0.903, 0.906, and 0.890 respectively. Agreement was maintained when adjusted for sex, age, diagnosis, liver fat content, and fat-water swap. Conclusion: Inline R2*-LIC provides robust and comparable quantification of LIC compared to FerriScan, without the need for offline post-processing. Key Points: • In patients being treated for iron overload with chelation therapy, liver iron concentration (LIC) is regularly assessed in order to monitor and adjust therapy. • Magnetic resonance imaging (MRI) is commonly used to quantify LIC. Several R2and R2* methods are available, all of which require offline post-processing. • A novel R2* MRI method allows for immediate calculation of LIC and provides comparable quantification of LIC to the FerriScan and recently published alternative R2* methods. [ABSTRACT FROM AUTHOR]

The nineteenth century witnessed the creation of a 'paper Panopticon' designed to capture information about offenders in England, especially those who were transported to Australia. This article considers the effectiveness of this new record-keeping system and asks whether convicts had some agency within it. These questions are explored through a macroscopic analysis of the recording of convict ages in nineteenth-century England and Australia, made possible by the Digital Panopticon project. By using the methodological opportunities opened up by digital technologies, we can test the accuracy of historical records in new ways, and in the process develop a better understanding of the encounter between state authority and convict agency. [ABSTRACT FROM AUTHOR]

This realist review of the literature provided a contemporary understanding of neighbourhoods and dementia and described how people living with dementia and their neighbourhood interacted via ongoing place-making and remaking processes. Drawing on 44 articles, neighbourhoods were revealed to have fluid and dynamic qualities where people with dementia used their strength and resources to connect to significant people and places. The review also indicated that the person with dementia–neighbourhood relationship was underpinned by four themes: 'home', 'social interactions', 'activities' and 'transportation'. Further research is encouraged to use innovative, participatory methods to explore the neighbourhood–dementia nexus in depth whilst paying close attention to social inclusion and diversity. [ABSTRACT FROM AUTHOR]

Digital self-management tools may aid young adults with sickle cell disease in addressing the self-management challenges they face in the initial years of transition from pediatric health services and improve health outcomes. The objective of this study was two-fold: (i) to examine the self-management challenges that young adults with sickle cell disease face, and (ii) identify the key components of a digital self-management program for young adults with sickle cell disease. A qualitative descriptive design using audio-recorded, transcribed, semi-structured focus group and individual interviews was conducted. Data were organized into themes using qualitative content analysis. Young adults (n = 33, 18-30 years old), healthcare providers (n = 24), and parents (n=3) from two urban tertiary care hospitals in Canada and USA participated in the study. Two main themes were identified: challenges to self-management and key components of a digital self-management program. Self-management challenges included 1) impact on livelihood and 2) emotional impact of sickle cell disease. Key components of a potential digital self-management program were focused on: 1) desired knowledge, 2) developing a care network and 3) developing self-advocacy skills. Young adults with sickle cell disease continue to face intersecting social and emotional challenges which impact self-management. They perceived a mobile-phone based self-management program could be an effective way to address their information needs, facilitate involvement of family, friends and partners in their self-management, and aid them in developing self-advocacy skills. These findings will be used to inform the development of a digital self-management program. [ABSTRACT FROM AUTHOR]

Background: Trait anxiety is characterized by impaired gating of threat from working memory (WM), allowing unnecessary maintenance of anxious cognitions. Improving filtering efficiency of threatening information through computerized WM training might reduce intrusive, worrisome thoughts. Methods: We randomized high-trait anxious individuals to 9 sessions of high-potency n-back (n = 19) or low-potency 1-back (n = 18) training to examine their effects on various neurocognitive indices of WM functioning and emotional symptoms. Results: Following the interventions, multilevel modeling analyses revealed both training conditions resulted in significant improvements in attentional (Flanker), WM capacity (operation and spatial span tasks), and WM filtering efficiency (change detection task) measures, and increased N2 amplitudes. However, the high-potency training produced more favorable results at post-training, indexed by larger ERN amplitudes. We also observed significant reductions in trait anxiety and worry symptoms for the high-potency training following the intervention, although, low-potency training caught up at follow-up with comparably reduced symptoms. Conclusions: These results show that emotional WM training can improve neurocognitive processes of attention and WM as well as symptoms of worrying. Overall, this study encourages the development of a standalone or adjunctive cognitive intervention focused on WM for vulnerable populations with high trait anxiety or worry symptoms. [ABSTRACT FROM AUTHOR]

Summary: We aimed to identify risk factors for adverse outcomes in pregnancies of women with sickle cell disease (SCD) and develop risk prediction models. Models were derived from a retrospective cohort of pregnant women with SCD and constructed using generalised estimating equation logistic regression, with clustering by woman. Maternal event(s) consisted of acute anaemia; cardiac, pulmonary, hepatobiliary, musculoskeletal, skin, splenic, neurological or renal complications, multi‐organ failure, venous thromboembolism, admission‐requiring vaso‐occlusive events (VOE), red cell transfusion, mortality or hypertensive disorder of pregnancy. Fetal events included preterm birth, small‐for‐gestational‐age or perinatal mortality. Of 199 pregnancies, 71% and 45% resulted in adverse maternal and fetal outcomes respectively. Low first‐trimester haemoglobin, admission‐requiring VOE in the year before pregnancy, multiple transfusions before pregnancy, SCD genotype and previous cardiac complications predicted maternal risk. Younger age and SCD genotype allowed early prediction of fetal risk (model‐F1). Adding maternal event(s) and high lactate dehydrogenase enabled re‐assessment of fetal risk with advancing gestation (model‐F2). Models were well calibrated and moderately discriminative for maternal outcome (c‐statistic 0·81, cross‐validated value 0·79) and fetal outcome (model‐F1 c‐statistic 0·68, cross‐validated value 0·65; model‐F2 c‐statistic 0·72, cross‐validated value 0·68). The models will allow early identification of women with SCD at high risk of adverse events, permitting early targeted interventions and ongoing fetal risk re‐assessment enabling intensification of surveillance and optimisation of delivery timing. [ABSTRACT FROM AUTHOR]

Chlorophyll fluorescence (ChlF) is a powerful non‐invasive technique for probing photosynthesis. Although proposed as a method for drought tolerance screening, ChlF has not yet been fully adopted in physiological breeding, mainly due to limitations in high‐throughput field phenotyping capabilities. The light‐induced fluorescence transient (LIFT) sensor has recently been shown to reliably provide active ChlF data for rapid and remote characterisation of plant photosynthetic performance. We used the LIFT sensor to quantify photosynthesis traits across time in a large panel of durum wheat genotypes subjected to a progressive drought in replicated field trials over two growing seasons. The photosynthetic performance was measured at the canopy level by means of the operating efficiency of Photosystem II (Fq′/Fm′) and the kinetics of electron transport measured by reoxidation rates (Fr1′ and Fr2′). Short‐ and long‐term changes in ChlF traits were found in response to soil water availability and due to interactions with weather fluctuations. In mild drought, Fq′/Fm′ and Fr2′ were little affected, while Fr1′ was consistently accelerated in water‐limited compared to well‐watered plants, increasingly so with rising vapour pressure deficit. This high‐throughput approach allowed assessment of the native genetic diversity in ChlF traits while considering the diurnal dynamics of photosynthesis. Photosynthetic performance of a large durum wheat panel under progressive drought in the field was quantified using the light‐induced fluorescence transient (LIFT) sensor for high‐throughput phenotyping. Photosynthesis traits showed high genetic variability, aiding physiological crop breeding. [ABSTRACT FROM AUTHOR]

Background: The monocyte-to-lymphocyte ratio (MLR) has been advocated as a biomarker in tuberculosis. Our objective was to evaluate its clinical value and associations. Methods: Blood counts, inflammatory markers and clinical parameters were measured in patients with and those screened for tuberculosis. Complete blood counts (CBCs) from a multi-ethnic population aged 16 to 65 years were evaluated; a sub-group with normal hematological indices was used to define the range of MLRs. Results: Multivariate analysis in proven tuberculosis (n = 264) indicated MLR associated with low serum albumin, high white cell counts and a positive culture; values were higher in sputum smear-positive pulmonary tuberculosis (S+PTB). Analysis in S+PTB (n = 296) showed higher MLRs in males and those with high neutrophil counts, low serum albumin and high C-reactive protein. The diagnostic value of MLRs was assessed by comparing notified patients with TB (n = 264) with denotified cases (n = 50), active case-finding in non-contacts (TB n = 111 and LTBI n = 373) and contacts of S+PTB (n = 149) with S+PTB found at screening (n = 75). Sensitivities and specificities ranged from 58.0–62.5% and 50.0–70.0% respectively for optimal cut-off values, defined by ROC curves. In CBCs obtained over one month, ratios correlated with neutrophil counts (ρ = 0.48, P<0.00001, n = 14,573; MLR = 0.45 at 8–8.9 x 109/L) and were higher in males than females (P<0.0001). The MLR range (mean ± 2SD) in those with normal hematological indices (n = 3921: females 0.122–0.474; males 0.136–0.505) paralleled LTBI MLRs. Ratios did not predict death (n = 29) nor response to treatment (n = 178 S+PTB with follow-up CBCs). Ratios were higher in males than female in the 16–45 years age group, where immune differences due to sex hormones are likely greatest. Conclusions: Severe tuberculosis and male sex associated with high MLRs; the same variables likely affect the performance of other biomarkers. The ratio performed poorly as a clinical aid. [ABSTRACT FROM AUTHOR]

The extent of social isolation experienced by people living with dementia who reside in the community has been well acknowledged, yet little is known about how people living alone with dementia maintain neighbourhood-based connections. The purpose of this study is to examine the experiences of people with dementia who live alone, focusing upon how they establish social networks and relationships in a neighbourhood context, and how they are supported to maintain this social context within everyday life. Multiple data collection methods were used including, semi-structured interviews, walking interviews, guided home tours and social network mapping, which were conducted with 14 community-dwelling people living alone with dementia (11 women and three men) situated across the three international study sites in England, Scotland and Sweden. Data were analysed using thematic analysis. The analysis revealed four main themes: (a) making the effort to stay connected; (b) befriending by organisations and facilitated friendships; (c) the quiet neighbourhood atmosphere; and (d) changing social connections. The analysis suggests that people with dementia who live alone were active agents who took control to find and maintain relationships and social networks in the neighbourhood. Our findings indicate the need to raise awareness about this specific group in both policy and practice, and to find creative ways to help people connect through everyday activities and by spontaneous encounters in the neighbourhood. [ABSTRACT FROM AUTHOR]

To support people with dementia to live at home, a key national and international policy driver is to create dementia-friendly communities which draws attention to the importance of a local neighbourhood and living well with dementia. However, there is a lack of evidence about how people with dementia define and interact with their neighbourhood. This longitudinal narrative research aimed to uncover the meaning, construction and place of neighbourhood in the lives of people with dementia and their care partners through a participatory approach. Five couples, where one partner had an early diagnosis of dementia and capacity to consent, participated in the (up to) one-year mixed qualitative method study. During this time-frame, 65 home visits were conducted, resulting in over 57 hours of interview data alongside the development of other artefacts, such as neighbourhood maps, photographs, diaries and field notes. Narrative analysis was applied within and across the data-sets. This led to the emergence of three themes to describe a connected neighbourhood. First, 'connecting to people' is about the couples' connections with family members, friends and neighbours through a sense of belonging, group identification and responsibilities. Second, 'connecting to places' shares the couples' emotional and biographical attachment to places. Third, 'connecting to resources' refers to the couples actively seeking support to live independently and to retain neighbourhood connections. [ABSTRACT FROM AUTHOR]

Sickle cell disease patients commonly present to an emergency department (ED) due to acute vaso-occlusive pain episodes (VOEs), also known as vaso-occlusive crises (VOCs). Unsatisfactory patient care leads to preventable morbidity, mortality, and substantial financial costs. This study investigated the current use of sickle cell disease patient-directed physician education (PDPE) in the clinical setting and also explored opportunities for improvement. A qualitative phenomenologic design was used with semi-structured in-depth interviews. Open-ended questions were used to probe participant's experiences with EDs, the feasibility of a PDPE program as well as barriers and facilitators to PDPE. A total of nine patients and eight physicians participated in the study. Three major themes were identified: divergent challenges to patient recommendations, new targets for sickle cell disease education and triage process: not heard and not seen. Numerous challenges exist to the implementation and optimization of PDPE with sickle cell disease triage processes and nursing support identified as influential factors. Paramount to the process of improving PDPE is physicians perceiving patients as credible sources of information, especially as it relates to generalized concerns of opioid dosing. A patient provided written or digital education tool can be considered to facilitate PDPE to ease communication strain on patients while increasing communication efficiency. [ABSTRACT FROM AUTHOR]

Current theories propose that anxiety adversely impacts working memory (WM) by restricting WM capacity and interfering with efficient filtering of task‐irrelevant information. The current study investigated the effect of shock‐induced state anxiety on WM capacity and the ability to filter task‐irrelevant neutral stimuli. We measured the contralateral delay activity (CDA), an event‐related potential that indexes the number of items maintained in WM, while participants completed a lateralized change detection task. The task included low and high WM loads, as well as a low load plus distracter condition. This design was used to assess WM capacity for low and high loads and investigate an individual's ability to filter neutral task‐irrelevant stimuli. Participants completed the task under two conditions, threat of shock and safe. We observed a reduced CDA in the threat compared to the safe condition that was specific for high memory load. However, we did not find any differences in CDA filtering cost between threat and safe conditions. In addition, we did not find any differences in behavioral performance between the threat and safe conditions. These findings suggest that being in an anxious state reduces the neural representation for large amounts of information in WM, but have little effect on the filtering of neutral distracters. Anxiety is believed to restrict working memory capacity and impact the ability to filter task‐irrelevant information, but little is known how an anxious state impacts these processes. Here, we provide electrophysiological evidence of reduced working memory capacity, but intact filtering abilities for neutral task‐irrelevant distracters in state anxious individuals. [ABSTRACT FROM AUTHOR]

This study explores the relationships between people living with dementia and their neighbourhood as they venture out from home on a regular and often routine basis. Here, we report findings from the Swedish field site of an international 5-year project: Neighbourhoods: our people, our places. The aims of this study were to investigate the lived experience of the neighbourhood for people with dementia and through this to better understand the meaning that neighbourhood held for the participants. In this study, we focus on the walking interviews which were conducted with 14 community-dwelling people with dementia (11 men and 3 women) and were analysed using an interpretative phenomenological method. Four themes were revealed from these interviews: life narratives embedded within neighbourhood; the support of selfhood and wellbeing through movement; the neighbourhood as an immediate social context; and restorative connections to nature. These themes were distilled into the 'essence' of what neighbourhood meant for the people we interviewed: A walkable area of subjective significance and social opportunity in which to move freely and feel rejuvenated. We have found that the neighbourhood for community-dwelling people with dementia holds a sense of attachment and offers the potential for freedom of movement. Our research indicates that a dementia diagnosis doesn't necessarily reduce this freedom of movement. The implications for practice and policy are considered: future research should explore and pay closer attention to the diverse living conditions of people living with dementia, and not least the particular challenges faced by people living alone with dementia. [ABSTRACT FROM AUTHOR]

The use of non-potable water (such as seawater) is an attractive alternative for water intensive processes such as biomass pretreatment and saccharification steps in the production of biochemicals and biofuels. Identification and application of halotolerant enzymes compatible with high-salt conditions may reduce the energy needed for non-potable water treatment and decrease waste treatment costs. Here we present the biochemical properties of a halotolerant endo-1,4-β-xylanase produced by Aspergillus clavatus in submerged fermentation, using paper sludge (XPS) and sugarcane bagasse (XSCB), and its potential application in the hydrolysis of agroindustrial residues. The peptide mass fingerprint and amino acid sequencing of the XPS and XSCB enzymes showed primary structure similarities with an endo-1,4-β-xylanase from Aspergillus clavatus (XYNA_ASPCL). Both enzyme preparations presented good thermal stability at 50 °C and were stable over a wide range of pH and Vmax up to 2450 U/mg for XPS. XPS and XSCB were almost fully stable even after 24 h of incubation in the presence of up to 3 M NaCl, and their activity were not affected by 500 mM NaCl. Both enzyme preparations were capable of hydrolyzing paper sludge and sugarcane bagasse to release reducing sugars. These characteristics make this xylanase attractive to be used in the hydrolysis of biomass, particularly with brackish water or seawater. [ABSTRACT FROM AUTHOR]

Background: Specialist LINK is a real-time, non-urgent telephone collaboration line designed to link family doctors and specialists. The purpose was to reduce wait times, improve efficiency and enhance the coordination of patient care through enhanced communication between primary and specialty care. The aim of this study was to determine the awareness and utilization of Specialist LINK and Primary Care Network (PCN) Clinical Pathways among family physicians. Methods: A family physician experience cross-sectional survey was conducted from March to May 2018 in Calgary and Area. The survey was designed to assess family physicians' awareness and utilization of Specialist LINK and PCN Clinical Pathways. We also used a 1–10 scale for respondents to rate the utility of Specialist LINK (1 was least useful and 10 represented highly useful). To obtain a true representative sample, family physicians were selected through a random sampling method. We applied multiple approaches to ensure a high response rate: paper survey, telephone reminders, and an on-site survey for non-responders. Results: A total of 251 participants completed the survey of the 650 randomly selected family physicians (Response rate≈39%). Eighty-nine percent of the family physicians were aware of Specialist LINK [95% Confidence Interval (84–92%)]. The average rating was 8.1 (on a scale of 1–10) for the usefulness of Specialist LINK. We found that the odds of being aware of Specialist LINK were two times higher in female family physicians compared to male physicians. Also, those with less than 5 years of experience, the odds of being aware of Specialist LINK were around five times higher compared to those with 5 or more years of experience. Fifty-five percent of family physicians were aware of PCN Clinical Pathways (95% CI = 48–60%); of those, 82% were accessing and following PCN Clinical Pathways in their clinical practice. The average rating was 7.9 (on a scale of 1–10) for the usefulness of PCN Clinical Pathways. Conclusion: Most of the respondents in Calgary and area were aware of Specialist LINK and a large proportion of them were using it to access advice for their patients. [ABSTRACT FROM AUTHOR]

β-glucosidases catalyze the hydrolysis β-1,4, β-1,3 and β-1,6 glucosidic linkages from non-reducing end of short chain oligosaccharides, alkyl and aryl β-D-glucosides and disaccharides. They catalyze the rate-limiting reaction in the conversion of cellobiose to glucose in the saccharification of cellulose for second-generation ethanol production, and due to this important role the search for glucose tolerant enzymes is of biochemical and biotechnological importance. In this study we characterize a family 3 glycosyl hydrolase (GH3) β-glucosidase (Bgl) produced by Malbranchea pulchella (MpBgl3) grown on cellobiose as the sole carbon source. Kinetic characterization revealed that the MpBgl3 was highly tolerant to glucose, which is in contrast to many Bgls that are completely inhibited by glucose. A 3D model of MpBgl3 was generated by molecular modeling and used for the evaluation of structural differences with a Bgl3 that is inhibited by glucose. Taken together, our results provide new clues to understand the glucose tolerance in GH3 β-glucosidases. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to compare clinical decision-making in iron overload patients using FerriScan and an R2*-based approach.Methods: One-hundred and six patients were imaged at two consecutive timepoints (454 ± 158 days) on a 1.5-T Siemens MAGNETOM Avanto Fit scanner. For both timepoints, patients underwent the standard FerriScan MRI protocol. During the second exam, each patient additionally underwent R2*-MRI mapping. For each patient, a retrospective (simulated) decision was made to increase, decrease, or maintain chelator levels. Two different decision models were considered: The fixed threshold model assumed that chelator adjustments are based strictly on fixed liver iron concentration (LIC) thresholds. Decisions made with this model depend only on the most recent LIC value and do not require any clinician input. The second model utilized decisions made by two hematologists retrospectively based on trends between two consecutive LIC values. Agreement (κA) between hematologists (i.e., interobserver variability) was compared with the agreement (κB) between a single hematologist using the two different LIC techniques.Results: Good agreement between R2*- and FerriScan-derived decisions was achieved for the fixed threshold model. True positive/negative rates were greater than 80%, and false positive/negative rates were less than 10%. ROC analysis yielded areas under the curve greater than 0.95. In the second model, the agreement in clinical decision-making for the two scenarios (κA vs. κB) was equal at the 95% confidence level.Conclusions: Switching to R2*-based LIC estimation from FerriScan has the same level of agreement in patient management decisions as does switching from one hematologist to another.Key Points: • Good agreement between R2*- and FerriScan-derived decisions in liver iron overload patient management • Switching to R2*-based LIC estimation from FerriScan has the same level of agreement in patient management decisions as does switching from one hematologist to another. [ABSTRACT FROM AUTHOR]

Objectives: The aim was to investigate the relationship between pancreatic and hepatic iron and fat to glucose metabolism in patients with iron overload and address conflicting results in literature as regards the relationship between pancreas iron and glucose dysregulation.Methods: We retrospectively evaluated pancreatic and hepatic R2*, fat fraction (FF), liver iron concentration (LIC), and glucose metabolism in 105 patients with iron overload obtained with a multi-echo gradient echo R2* technique and assessed the correlation between pancreatic R2* and FF to glucose dysregulation.Results: There were no significant differences in pancreatic R2*, liver R2*, and FF in patients with iron overload and glucose dysregulation compared to those with normoglycemia (p = 0.435, p = 0.674, and p = 0.976), whereas pancreatic FF was significantly higher, 23.5% vs 16.7% respectively (p = 0.011). Pancreatic FF and R2* demonstrated an area under the curve of 0.666 and 0.571 for discriminating glucose dysregulation. Pancreatic FF of 26.2% yielded specificity and sensitivity of 80% and 45% for prediction of glucose dysregulation. Pancreatic R2* weakly correlated with pancreatic FF, r = 0.388 (p < 0.001), and liver R2*, r = 0.201 (p = 0.033), and showed no correlation with hepatic FF r = -0.013 (p = 0.892) or LIC categories (p = 0.493).Conclusion: Pancreatic FF but not pancreatic R2* was associated with glucose dysregulation in patients with iron overload. Prior studies reporting correlation of pancreatic R2* to glucose dysregulation likely relate from inadequate MRI technique or analysis employed, which unlike our study did not perform simultaneous measurements of fat and iron essential to avoid their confounding effects during quantitative analysis.Key Points: • Pancreatic fat fraction, unlike iron, is associated with glucose dysregulation in iron overload. • Simultaneous measurement of pancreatic iron and fat content with MRI is essential to avoid confounding effects of one another during quantitative analysis. • Pancreatic fat fraction could be utilized to predict glucose dysregulation in iron overload states. [ABSTRACT FROM AUTHOR]