Publications by authors named "S Hazirah Adam"

850 Publications

No Association Between or Polymorphisms and Gestational Diabetes Mellitus in South African Women.

Diabetes Metab Syndr Obes 2021 24;14:791-800. Epub 2021 Feb 24.

Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Cape Town, 7505, South Africa.

Purpose: Gestational diabetes mellitus (GDM) is a growing public health concern. GDM affects approximately 14% of pregnancies globally, and without effective treatment, is associated with short- and long-term complications in mother and child. Lower serum adiponectin concentrations and aberrant DNA methylation have been reported during GDM. The aim of this study was to investigate the association between the -11377C>G and -11391G>A, and methylenetetrahydrofolate reductase 677C>T polymorphisms and GDM in a population of black South African women.

Materials And Methods: DNA was isolated from the peripheral blood of 447 pregnant women with (n=116) or without (n=331) GDM, where after (rs266729 and rs17300539) and (rs1801133) polymorphisms were genotyped using TaqMan Quantitative Real-Time PCR analysis.

Results: Women with GDM had a higher body mass index (p=0.012), were more insulin resistant (p<0.001) and had lower adiponectin levels (p=0.013) compared to pregnant women with normoglycemia. Genotypic, dominant and recessive genetic models showed no association between rs266729 and rs17300539 and rs1801133 polymorphisms and GDM. Intriguingly, the risk G allele of rs266729 was associated with higher fasting glucose and insulin concentrations, while the T allele in rs1801133 was associated with higher fasting insulin concentrations only.

Conclusion: rs266729 and rs17300539 and rs1801133 polymorphisms are not associated with GDM in a population of black South African women. These findings suggest that these single nucleotide polymorphisms (SNPs) do not individually increase GDM risk in the African population. However, the role of these SNPs in possible gene-gene or gene-environment interactions remain to be established.
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http://dx.doi.org/10.2147/DMSO.S294328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917309PMC
February 2021

Tunable Optical Properties of Thin Films Controlled by the Interface Twist Angle.

Nano Lett 2021 Feb 16. Epub 2021 Feb 16.

Department of Materials Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02141, United States.

Control of materials properties has been the driving force of modern technologies. So far, materials properties have been modulated by their composition, structure, and size. Here, by using cathodoluminescence in a scanning transmission electron microscope, we show that the optical properties of stacked, >100 nm thick hexagonal boron nitride (hBN) films can be continuously tuned by their relative twist angles. Due to the formation of a moiré superlattice between the two interface layers of the twisted films, a new moiré sub-band gap is formed with continuously decreasing magnitude as a function of the twist angle, resulting in tunable luminescence wavelength and intensity increase of >40×. Our results demonstrate that moiré phenomena extend beyond monolayer-based systems and can be preserved in a technologically relevant, bulklike material at room temperature, dominating optical properties of hBN films for applications in medicine, environmental, or information technologies.
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http://dx.doi.org/10.1021/acs.nanolett.0c04924DOI Listing
February 2021

Adiponectin as a Potential Biomarker for Pregnancy Disorders.

Int J Mol Sci 2021 Jan 29;22(3). Epub 2021 Jan 29.

Department of Obstetrics and Gynaecology, University of Pretoria, Private Bag X169, Pretoria 0001, South Africa.

Adiponectin is an adipocyte-derived hormone that plays a critical role in energy homeostasis, mainly attributed to its insulin-sensitizing properties. Accumulating studies have reported that adiponectin concentrations are decreased during metabolic diseases, such as obesity and type 2 diabetes, with an emerging body of evidence providing support for its use as a biomarker for pregnancy complications. The identification of maternal factors that could predict the outcome of compromised pregnancies could act as valuable tools that allow the early recognition of high-risk pregnancies, facilitating close follow-up and prevention of pregnancy complications in mother and child. In this review we consider the role of adiponectin as a potential biomarker of disorders associated with pregnancy. We discuss common disorders associated with pregnancy (gestational diabetes mellitus, preeclampsia, preterm birth and abnormal intrauterine growth) and highlight studies that have investigated the potential of adiponectin to serve as biomarkers for these disorders. We conclude the review by recommending strategies to consider for future research.
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http://dx.doi.org/10.3390/ijms22031326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866110PMC
January 2021

Computational analyses reveal spatial relationships between nuclear pore complexes and specific lamins.

J Cell Biol 2021 Apr;220(4)

Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL.

Nuclear lamin isoforms form fibrous meshworks associated with nuclear pore complexes (NPCs). Using datasets prepared from subpixel and segmentation analyses of 3D-structured illumination microscopy images of WT and lamin isoform knockout mouse embryo fibroblasts, we determined with high precision the spatial association of NPCs with specific lamin isoform fibers. These relationships are retained in the enlarged lamin meshworks of Lmna-/- and Lmnb1-/- fibroblast nuclei. Cryo-ET observations reveal that the lamin filaments composing the fibers contact the nucleoplasmic ring of NPCs. Knockdown of the ring-associated nucleoporin ELYS induces NPC clusters that exclude lamin A/C fibers but include LB1 and LB2 fibers. Knockdown of the nucleoporin TPR or NUP153 alters the arrangement of lamin fibers and NPCs. Evidence that the number of NPCs is regulated by specific lamin isoforms is presented. Overall the results demonstrate that lamin isoforms and nucleoporins act together to maintain the normal organization of lamin meshworks and NPCs within the nuclear envelope.
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http://dx.doi.org/10.1083/jcb.202007082DOI Listing
April 2021

High density lipoprotein-associated miRNA is increased following Roux-en-Y gastric bypass surgery for severe obesity.

J Lipid Res 2021 Feb 5:100044. Epub 2021 Feb 5.

Lipid Research Group, Division of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom; Cardiovascular Trials Unit, Manchester University NHS Foundation Trust, Manchester, United Kingdom. Electronic address:

Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed weight-loss procedures, but how severe obesity and RYGB affect circulating HDL-associated microRNAs (miRNAs) remains unclear. Here, we aim to investigate how HDL-associated miRNAs are regulated in severe obesity and how weight loss after RYGB surgery affects HDL-miRNAs. Plasma HDLs were isolated from patients with severe obesity (n = 53) before and 6 and 12 months after RYGB by immunoprecipitation using goat anti-human apoA-I microbeads. HDLs were also isolated from 18 healthy participants. miRNAs were extracted from isolated HDL and levels of miR-24, miR-126, miR-222, and miR-223 were determined by TaqMan miRNA assays. We found that HDL-associated miR-126, miR-222, and miR-223 levels, but not miR-24 levels, were significantly higher in patients with severe obesity when compared with healthy controls. There were significant increases in HDL-associated miR-24, miR-222, and miR-223 at 12 months after RYGB. Additionally, cholesterol efflux capacity and paraoxonase activity were increased and intercellular adhesion molecule-1 (ICAM-1) levels decreased. The increases in HDL-associated miR-24 and miR-223 were positively correlated with an increase in cholesterol efflux capacity (r = 0.326, P=0.027 and r = 0.349, P = 0.017, respectively). An inverse correlation was observed between HDL-associated miR-223 and ICAM-1 at baseline. Together, these findings show that HDL-associated miRNAs are differentially regulated in healthy participants versus patients with severe obesity and are altered after RYGB. These findings provide insights into how miRNAs are regulated in obesity before and after weight reduction and may lead to the development of novel treatment strategies for obesity and related metabolic disorders.
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http://dx.doi.org/10.1194/jlr.RA120000963DOI Listing
February 2021

Progress in Epitaxial Thin-Film Na Bi as a Topological Electronic Material.

Adv Mater 2021 Feb 3:e2005897. Epub 2021 Feb 3.

Australian Research Council Centre of Excellence in Future Low-Energy Electronics Technologies, Monash University, Clayton, Victoria, 3800, Australia.

Trisodium bismuthide (Na Bi) is the first experimentally verified topological Dirac semimetal, and is a 3D analogue of graphene hosting relativistic Dirac fermions. Its unconventional momentum-energy relationship is interesting from a fundamental perspective, yielding exciting physical properties such as chiral charge carriers, the chiral anomaly, and weak anti-localization. It also shows promise for realizing topological electronic devices such as topological transistors. Herein, an overview of the substantial progress achieved in the last few years on Na Bi is presented, with a focus on technologically relevant large-area thin films synthesized via molecular beam epitaxy. Key theoretical aspects underpinning the unique electronic properties of Na Bi are introduced. Next, the growth process on different substrates is reviewed. Spectroscopic and microscopic features are illustrated, and an analysis of semiclassical and quantum transport phenomena in different doping regimes is provided. The emergent properties arising from confinement in two dimensions, including thickness-dependent and electric-field-driven topological phase transitions, are addressed, with an outlook toward current challenges and expected future progress.
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http://dx.doi.org/10.1002/adma.202005897DOI Listing
February 2021

Effect of bariatric surgery on plasma levels of oxidised phospholipids, biomarkers of oxidised LDL and lipoprotein(a).

J Clin Lipidol 2020 Dec 11. Epub 2020 Dec 11.

Department of Medicine, Manchester University NHS Foundation Trust, Manchester, UK; Lipid Research Group, Division of Medical Sciences, The University of Manchester, Manchester, UK. Electronic address:

Background: Obesity is associated with adverse cardiovascular outcomes and this is improved following bariatric surgery. Oxidised phospholipids (OxPL) are thought to reflect the pro-inflammatory effects of lipoprotein(a) [Lp(a)], and both are independent predictors of cardiovascular disease.

Objective: Our study sought to determine the impact of bariatric surgery on OxPL, biomarkers of oxidised LDL (OxLDL) and Lp(a).

Methods: This is a prospective, observational study of 59 patients with severe obesity undergoing bariatric surgery. Blood samples were obtained prior to surgery and at 6 and 12 months after. Sixteen patients attending the tertiary medical weight management clinic at the same centre were also recruited for comparison. Lipid and metabolic blood parameters, OxLDL, OxPL on apolipoprotein B-100 (OxPL-apoB), IgG and IgM autoantibodies to MDA-LDL, IgG and IgM apoB-immune complexes and Lp(a) were measured.

Results: Reduction in body mass index (BMI) was significant following bariatric surgery, from median 48 kg/m at baseline to 37 kg/m at 6 months and 33 kg/m at 12 months. OxPL-apoB levels decreased significantly at 12 months following surgery [5.0 (3.2-7.4) to 3.8 (3.0-5.5) nM, p = 0.001], while contrastingly, Lp(a) increased significantly [10.2 (3.8-31.9) to 16.9 (4.9-38.6) mg/dl, p = 0.002]. There were significant post-surgical decreases in IgG and IgM biomarkers, particularly at 12 months, while OxLDL remained unchanged.

Conclusions: Bariatric surgery results in a significant increase in Lp(a) but reductions in OxPL-apoB and other biomarkers of oxidised lipoproteins, suggesting increased synthetic capacity and reduced oxidative stress. These biomarkers might be clinically useful to monitor physiological effects of weight loss interventions.
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http://dx.doi.org/10.1016/j.jacl.2020.12.002DOI Listing
December 2020

Bariatric surgery leads to an improvement in small nerve fibre damage in subjects with obesity.

Int J Obes (Lond) 2021 Mar 27;45(3):631-638. Epub 2021 Jan 27.

Division of Cardiovascular Sciences, School of Medical Sciences, Core Technology Facility, University of Manchester, Manchester, UK.

Introduction: Subjects with obesity have metabolic risk factors for nerve fibre damage. Because bariatric surgery improves these risk factors we have assessed whether this can ameliorate nerve fibre damage.

Methods: Twenty-six obese subjects without diabetes (age: 46.23 ± 8.6, BMI: 48.7 ± 1.5, HbA1c: 38.0 ± 4.5) and 20 controls (age: 48.3 ± 6.2, BMI: 26.8 ± 4.2, HbA1c: 39.1 ± 2.6) underwent detailed assessment of neuropathy at baseline and 12 months after bariatric surgery.

Results: Obese subjects had normal peroneal (45.9 ± 5.5 vs. 48.1 ± 4.5, P = 0.1) and sural (46.9 ± 7.6 vs. 47.9 ± 10.6, P = 0.1) nerve conduction velocity, but a significantly higher neuropathy symptom profile (NSP) (4.3 ± 5.7 vs. 0.3 ± 0.6, P = 0.001), vibration perception threshold (VPT) (V) (10.2 ± 6.8 vs. 4.8 ± 2.7, P < 0.0001), warm threshold (C°) (40.4 ± 3.5 vs. 37.2 ± 1.8, P = 0.003) and lower peroneal (3.8 ± 2.2 vs. 4.9 ± 2.2, P = 0.02) and sural (8.9 ± 5.8 vs. 15.2 ± 8.5, P < 0.0001) nerve amplitude, deep breathing-heart rate variability (DB-HRV) (beats/min) (21.7 ± 4.1 vs. 30.1 ± 14, P = 0.001), corneal nerve fibre density (CNFD) (n/mm) (25.6 ± 5.3 vs. 32.0 ± 3.1, P < 0.0001), corneal nerve branch density (CNBD) (n/mm) (56.9 ± 27.5 vs. 111.4 ± 30.7, P < 0.0001) and corneal nerve fibre length (CNFL) (mm/mm) (17.9 ± 4.1 vs. 29.8 ± 4.9, P < 0.0001) compared to controls at baseline. In control subjects there was no change in neuropathy measures over 12 months. However, 12 months after bariatric surgery there was a significant reduction in BMI (33.7 ± 1.7 vs. 48.7 ± 1.5, P = 0.001), HbA1c (34.3 ± 0.6 vs. 38.0 ± 4.5, P = 0.0002), triglycerides (mmol/l) (1.3 ± 0.6 vs. 1.6 ± 0.8, P = 0.005) and low-density lipoprotein cholesterol (mmol/l) (2.7 ± 0.7 vs. 3.1 ± 0.9, P = 0.02) and an increase in high-density lipoprotein cholesterol (mmol/l) (1.2 ± 0.3 vs. 1.04 ± 0.2, P = 0.002). There was a significant improvement in NSP (1.6 ± 2.7 vs. 4.3 ± 5.7, P = 0.004), neuropathy disability score (0.3 ± 0.9 vs. 1.3 ± 2.0, P = 0.03), CNFD (28.2 ± 4.4 vs. 25.6 ± 5.3, P = 0.03), CNBD (64.7 ± 26.1 vs. 56.9 ± 27.5, P = 0.04) and CNFL (20.4 ± 1.2 vs. 17.9 ± 4.1, P = 0.02), but no change in cold and warm threshold, VPT, DB-HRV or nerve conduction velocity and amplitude. Increase in CNFD correlated with a decrease in triglycerides (r = -0.45, P = 0.04).

Conclusion: Obese subjects have evidence of neuropathy, and bariatric surgery leads to an improvement in weight, HbA1c, lipids, neuropathic symptoms and deficits and small nerve fibre regeneration without a change in quantitative sensory testing, autonomic function or neurophysiology.
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http://dx.doi.org/10.1038/s41366-020-00727-9DOI Listing
March 2021

Structures of the archaerhodopsin-3 transporter reveal that disordering of internal water networks underpins receptor sensitization.

Nat Commun 2021 01 27;12(1):629. Epub 2021 Jan 27.

Biochemistry Department, Oxford University, South Parks Road, Oxford, OX1 3QU, UK.

Many transmembrane receptors have a desensitized state, in which they are unable to respond to external stimuli. The family of microbial rhodopsin proteins includes one such group of receptors, whose inactive or dark-adapted (DA) state is established in the prolonged absence of light. Here, we present high-resolution crystal structures of the ground (light-adapted) and DA states of Archaerhodopsin-3 (AR3), solved to 1.1 Å and 1.3 Å resolution respectively. We observe significant differences between the two states in the dynamics of water molecules that are coupled via H-bonds to the retinal Schiff Base. Supporting QM/MM calculations reveal how the DA state permits a thermodynamic equilibrium between retinal isomers to be established, and how this same change is prevented in the ground state in the absence of light. We suggest that the different arrangement of internal water networks in AR3 is responsible for the faster photocycle kinetics compared to homologs.
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http://dx.doi.org/10.1038/s41467-020-20596-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840839PMC
January 2021

Corneal confocal microscopy identifies small fibre damage and progression of diabetic neuropathy.

Sci Rep 2021 Jan 21;11(1):1859. Epub 2021 Jan 21.

Department of Medicine, Manchester University NHS Foundation Trust, Manchester, UK.

Accurately quantifying the progression of diabetic peripheral neuropathy is key to identify individuals who will progress to foot ulceration and to power clinical intervention trials. We have undertaken detailed neuropathy phenotyping to assess the longitudinal utility of different measures of neuropathy in patients with diabetes. Nineteen patients with diabetes (age 52.5 ± 14.7 years, duration of diabetes 26.0 ± 13.8 years) and 19 healthy controls underwent assessment of symptoms and signs of neuropathy, quantitative sensory testing, autonomic nerve function, neurophysiology, intra-epidermal nerve fibre density (IENFD) and corneal confocal microscopy (CCM) to quantify corneal nerve fibre density (CNFD), branch density (CNBD) and fibre length (CNFL). Mean follow-up was 6.5 years. Glycated haemoglobin (p = 0.04), low-density lipoprotein-cholesterol (LDL-C) (p = 0.0009) and urinary albumin creatinine ratio (p < 0.0001) improved. Neuropathy symptom profile (p = 0.03), neuropathy disability score (p = 0.04), vibration perception threshold (p = 0.02), cold perception threshold (p = 0.006), CNFD (p = 0.03), CNBD (p < 0.0001), CNFL (p < 0.0001), IENFD (p = 0.04), sural (p = 0.02) and peroneal motor nerve conduction velocity (p = 0.03) deteriorated significantly. Change (∆) in CNFL correlated with ∆CPT (p = 0.006) and ∆Expiration/Inspiration ratio (p = 0.002) and ∆IENFD correlated with ∆CNFD (p = 0.005), ∆CNBD (p = 0.02) and ∆CNFL (p = 0.01). This study shows worsening of diabetic neuropathy across a range of neuropathy measures, especially CCM, despite an improvement in HbA1c and LDL-C. It further supports the utility of CCM as a rapid, non-invasive surrogate measure of diabetic neuropathy.
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http://dx.doi.org/10.1038/s41598-021-81302-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820596PMC
January 2021

Optimising Awareness and Knowledge of Breast Cancer Screening for Nurses Through Train-the-Trainer Workshops.

J Cancer Educ 2021 Jan 21. Epub 2021 Jan 21.

College of Nursing, Ras Al Khaimah Medical & Health Sciences University, Ras Al Khaimah, United Arab Emirates.

Nurses play an important role in educating patients on breast cancer and have a positive influence in encouraging women to participate in breast screening. This current study aimed to use a train-the-trainer model to improve the level of knowledge of nurses on breast cancer and screening in Ras Al Khaimah, United Arab Emirates. The study also focused on the nurses' ability to train other nurses in assisting women to engage in breast screening. This interventional study used a mixed-method design. Seventeen female nurses (aged 28-60 years) were recruited from public and private health centers and participated in a breast cancer train-the-trainer workshop. They completed a survey before and after the workshop. The surveys included a series of open and closed questions to assess their knowledge of breast cancer symptoms, risk factors, diagnosis, and patient communication. The study found that nurse participants had good baseline knowledge of breast cancer topics, including breast self-examinations, clinical breast examinations, and mammography. Responses were deemed accurate if they answered open-ended questions without incorrect information and correct options were selected in the quantitative sections. However, training improved the detail and accuracy of the participant responses. Training also improved the confidence of nurse participants to teach other women and nurses how to perform breast self-examinations and provide breast cancer information. There were significant increases in nurse participants' knowledge of risk factors (p < 0.001, r = 0.6) and symptoms (p = 0.003, r = 0.5). The nurse participants perceived that health education was the best means of encouraging women to participate in breast screening.
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http://dx.doi.org/10.1007/s13187-020-01942-8DOI Listing
January 2021

Corneal Keratocyte Density and Corneal Nerves Are Reduced in Patients With Severe Obesity and Improve After Bariatric Surgery.

Invest Ophthalmol Vis Sci 2021 Jan;62(1):20

Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.

Purpose: Obesity is associated with peripheral neuropathy, which bariatric surgery may ameliorate. The aim of this study was to assess whether corneal confocal microscopy can show a change in corneal nerve morphology and keratocyte density in subjects with severe obesity after bariatric surgery.

Methods: Twenty obese patients with diabetes (n = 13) and without diabetes (n = 7) underwent assessment of hemoglobin A1c (HbA1c), lipids, IL-6, highly sensitive C-reactive protein (hsCRP), and corneal confocal microscopy before and 12 months after bariatric surgery. Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), and keratocyte density (KD) from the anterior, middle, and posterior stroma were quantified. Twenty-two controls underwent assessment at baseline only.

Results: CNFL (P < 0.001), CNBD (P < 0.05), and anterior (P < 0.001), middle (P < 0.001), and posterior (P < 0.001) keratocyte densities were significantly lower in obese patients compared to controls, and anterior keratocyte density (AKD) correlated with CNFL. Twelve months after bariatric surgery, there were significant improvements in body mass index (BMI; P < 0.001), HDL cholesterol (P < 0.05), hsCRP (P < 0.001), and IL-6 (P < 0.01). There were significant increases in CNFD (P < 0.05), CNBD (P < 0.05), CNFL (P < 0.05), and anterior (P < 0.05) and middle (P < 0.001) keratocyte densities. The increase in AKD correlated with a decrease in BMI (r = -0.55, P < 0.05) and triglycerides (r = -0.85, P < 0.001). There were no significant correlations between the change in keratocyte densities and corneal nerve fiber or other neuropathy measures.

Conclusions: Corneal confocal microscopy demonstrates early small fiber damage and reduced keratocyte density in obese patients. Bariatric surgery leads to weight reduction and improvement in lipids and inflammation and an improvement in keratocyte density and corneal nerve regeneration.
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http://dx.doi.org/10.1167/iovs.62.1.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817877PMC
January 2021

Utilization of telehealth in paediatric genome-wide sequencing: Health services implementation issues in the CAUSES Study.

J Telemed Telecare 2021 Jan 20:1357633X20982737. Epub 2021 Jan 20.

Department of Medical Genetics, University of British Columbia, Canada.

Introduction: Genome-wide sequencing (exome or whole genome) is transforming the care and management of paediatric patients with a rare disease because of its diagnostic capabilities. Genome-wide sequencing is most effective when both parents and the child are sequenced as a trio. Genetic counselling is recommended for all families considering genome-wide sequencing. Although telehealth is well established in genetic counselling for hereditary cancer and prenatal genetics, its use with genome-wide sequencing has not been well studied. The CAUSES Clinic at BC Children's and Women's Hospitals was a translational paediatric trio-based genome-wide sequencing initiative. Pre-test genetic counselling via telehealth (at a clinical site near the family's residence) was offered to families who had been previously evaluated by a clinical geneticist. We report on the first 300 families seen in the CAUSES clinic and compare health services implementation issues of families seen via telehealth versus on-site.

Methods: Demographics, cost to families (travel and time), time to first appointment, complete trio sample accrual and diagnostic rates were studied.

Results: Of the 300 patients, 58 (19%) were seen via telehealth and 242 (81%) were seen on-site for pre-test counselling. The mean time to completion of accrual of trio samples in the telehealth group was 56.3 (standard deviation ±87.3) days versus 18.9 (standard deviation ±62.4) days in the onsite group ( < 2.2 × 10). The mean per-family estimated actual or potential travel/time cost savings were greater in the telehealth group (Can$987; standard deviation = Can$1151) than for those seen on-site (Can$305; standard deviation = Can$589) ( = 0.0004).

Conclusions: Telehealth allowed for access to genome-wide sequencing for families in remote communities and for them to avoid significant travel and time costs; however, there was a significant delay to accrual of the complete trio samples in the telehealth group, impacting on time of result reporting and delaying diagnoses for families for whom genome-wide sequencing was diagnostic.
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http://dx.doi.org/10.1177/1357633X20982737DOI Listing
January 2021

Thromboprophylaxis for orthopedic surgery; An updated meta-analysis.

Thromb Res 2020 Dec 28;199:43-53. Epub 2020 Dec 28.

Duke University, Division of Hematology, Department of Medicine, Durham, NC, USA.

Background: Venous thromboembolism (VTE) is a serious complication of orthopedic surgery. Low molecular weight heparin (LMWH) has been the standard of care for thromboprophylaxis in this population. However, direct oral anticoagulants (DOACs) are increasingly being used as alternatives.

Objective: To assess the efficacy and safety of DOACs versus LMWH for thromboprophylaxis in orthopedic surgery.

Methods: We searched MEDLINE, Embase, and the Cochrane Collaboration Central Register of Controlled Trials from inception until April 2020, for randomized controlled trials (RCTs) comparing DOACs with LMWH for thromboprophylaxis in orthopedic surgery.

Results: Twenty-five RCTs met inclusion criteria, including 40,438 patients, with a mean age of 68 years and 50% were males. Compared to LMWH, DOACs were associated with a significant reduction of major VTE; defined as the composite events of proximal deep vein thrombosis (DVT), pulmonary embolism (PE), and VTE-related mortality (RR 0.33; 95% CI: 0.20-0.53; P<0.01), and total DVT (RR: 0.59; 95% CI: 0.48-0.73; P<0.01), but not PE (RR 0.81; 95% CI: 0.49-1.34; P=0.42). There was no statistically significant difference between both groups on the incidence of major bleeding (RR 0.99; 95% CI: 0.77-1.27; P=0.92), clinically relevant non-major bleeding (RR 1.04; 95% CI: 0.92-1.17; P=0.52), all-cause mortality (RR 1.06; 95% CI: 0.64-1.76; P=0.83), VTE-related mortality (RR 0.84; 95% CI: 0.40-1.74; P=0.64) and bleeding-related mortality (RR 1.24; 95% CI: 0.30-5.18; P=0.77).

Conclusion: For patients undergoing orthopedic surgery, thromboprophylaxis with DOACs is associated with a significant reduction of major VTE and DVT, compared to LMWH. Safety outcomes were not significantly different between both treatment groups.
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http://dx.doi.org/10.1016/j.thromres.2020.12.007DOI Listing
December 2020

Network for biomarker immunoprofiling for cancer immunotherapy: Cancer Immune Monitoring and Analysis Centers and Cancer Immunologic Data Commons (CIMAC-CIDC).

Clin Cancer Res 2021 Jan 8. Epub 2021 Jan 8.

Cancer Diagnosis Program, DCTD, Cancer Diagnosis Program, DCTD, National Cancer Institute

Immunoprofiling to identify biomarkers and integration with clinical trials outcome are critical to improve immunotherapy approaches for cancer patients. However, the translational potential of individual studies is often limited by small sample size of trials and the complexity of immuno-oncology biomarkers. Variability in assays further limits comparison and interpretation of data across studies and laboratories. To enable a systematic approach to biomarker identification and correlation with clinical outcome across trials, the Cancer Immune Monitoring and Analysis Centers and Cancer Immunologic Data Commons (CIMAC-CIDC) Network was established through support of the Cancer MoonshotSM Initiative of the National Cancer Institute and the Partnership for Accelerating Cancer Therapies (PACT) with industry partners via the Foundation for the National Institutes of Health. The CIMAC-CIDC Network is composed of four academic centers (CIMACs) with multidisciplinary expertise in the field of cancer immunotherapy that provide validated and harmonized assays for immune profiling. A data coordinating center (CIDC) provides the computational expertise and resources for biomarker data storage and analysis platforms for correlation with clinical data. This overview highlights strategies for assay harmonization to enable cross-trial and cross-site data analysis and describes key elements for establishing a network to enhance immuno-oncology biomarker development. These include an operational infrastructure; validation and harmonization of core immunoprofiling assays; platforms for data ingestion and integration; and access to specimens from clinical trials. Published in the same volume are reports of harmonization for core analyses: whole exome sequencing, RNA sequencing, cytometry by time of flight, and immunohistochemistry/immunofluorescence.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3241DOI Listing
January 2021

Skin cancers in people with albinism in Togo in 2019: results of two rounds of national mobile skin care clinics.

BMC Cancer 2021 Jan 5;21(1):26. Epub 2021 Jan 5.

Dermatology and STIs Department, Service de dermatolgie et IST, CHU Sylvanus Olympio, Université de Lomé, BP. 30785, Lomé, Togo.

Background: In people with albinism (PWA), the deficiency of melanin increase the risk of skin cancers. The aim of this study was to determine the prevalence of skin cancers and characteristics of these detected skin cancers (histological types, localization) in PWA in 10 cities in Togo in 2019.

Methods: This is a cross-sectional study of medical records of PWA systematically examined during two mobile skin care clinics in 2019, as part of a programme for the prevention and management of skin cancers in these subjects.

Results: During the study period, 280 (95.2%) of the 294 PWA consulted, had developed skin lesions. Of the 280 PWA, the pathological reports from the medical records of 33 patients (11.8%; (95%CI = [8.2-16.2]) had concluded to non-melanoma skin cancers. The mean age of these 33 patients was 38.6 ± 15.2 years and the sex-ratio was 1. Their occupations were mainly resellers (21.2%), traders (15.2%) and farmers (12.2%). In the 33 patients, 54 cases of non-melanoma skin cancers were identified, with some patients having more than one tumor, and some of them having more than one (histologically confirmed) diagnosis. These 54 non-melanoma skin cancers were divided into 21 cases of invasive squamous cell carcinomas, 2 cases of Bowen's disease and 31 cases of basal cell carcinomas. These non-melanoma skin cancers mainly occurred in the head and neck (33 cases; 61.1%), the upper limbs (15 cases; 27, 8%) and the trunk (4 cases; 7.4%).

Conclusion: The results of this study show a high prevalence of skin cancers among PWAs in Togo in 2019, only non-melanoma skin cancers. In addition, they illustrate the role of ultraviolet rays with regard to the localization of skin cancers and the occupations of patients. Popularization and compliance with photo protection measures, systematic and regular examination of the skin of these PWAs will allow early detection and treatment of these skin cancers.
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http://dx.doi.org/10.1186/s12885-020-07747-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786986PMC
January 2021

GC-MS Evaluation, Antioxidant Content, and Cytotoxic Activity of Propolis Extract from Peninsular Malaysian Stingless Bees, .

Evid Based Complement Alternat Med 2020 9;2020:8895262. Epub 2020 Dec 9.

Integrative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, SAINS@BERTAM, 13200 Kepala Batas, Penang, Malaysia.

Introduction: Propolis has been used traditionally in several countries for treating various diseases as it possessed healing properties including antioxidant and anticancer qualities. In Peninsular Malaysia, is one of the species of stingless bees mainly found in virgin jungle reserves which largely contribute to propolis production. Therefore, this study is designed to evaluate the phytochemical contents, antioxidant properties, and the cytotoxic effect of ethanolic crude of propolis extract against MCF7 and MCF 10A cell lines.

Method: The ethanolic extract of propolis (EEP) was extracted using 80% ethanol. Identification of phytochemical contents and antioxidant properties of EEP was analysed by gas chromatography-mass spectrometry (GC-MS) and using 2, 2'-azinobis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) method, respectively. The EEP cytotoxic activity was evaluated on MCF7 and MCF 10A using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay.

Results: Phytochemical contents of EEP demonstrated 28 compounds in which caryophyllene (99%), -amyrin (96%), -amyrin (93%), and caryophyllene oxide (93%) were the main compounds. The percentage of ABTS scavenging activity of EEP showed an inhibition of 9.5% with half-inhibitory concentration (IC) value of 1.68 mg/mL. The EEP reduced MCF7 cells viability at IC value of 62.24 g/mL, 44.15 g/mL, and 32.70 g/mL at 24, 48, and 72 hours, respectively. The IC value of MCF 10A was 49.55 g/mL, 56.05 g/mL, and 72.10 g/mL at 24, 48, and 72 hours, respectively. The EEP cytotoxic effect of was more selective towards MCF7 at 72-hour incubation with a selectivity index (SI) of 2.20.

Conclusion: The EEP has been shown to have antioxidants and potential bioactive compounds and inhibited proliferation of the MCF7 cells. Further studies on the EEP role in the apoptosis pathway and its screening towards other cell lines will be evaluated.
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http://dx.doi.org/10.1155/2020/8895262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759394PMC
December 2020

Frontiers in Multiscale Modeling of Photoreceptor Proteins.

Photochem Photobiol 2020 Dec 28. Epub 2020 Dec 28.

Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.

This perspective article highlights the challenges in the theoretical description of photoreceptor proteins using multiscale modeling, as discussed at the CECAM workshop in Tel Aviv, Israel. The participants have identified grand challenges and discussed the development of new tools to address them. Recent progress in understanding representative proteins such as green fluorescent protein, photoactive yellow protein, phytochrome, and rhodopsin is presented, along with methodological developments.
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http://dx.doi.org/10.1111/php.13372DOI Listing
December 2020

Making tiestalls more comfortable: II. Increasing chain length to improve the ease of movement of dairy cows.

J Dairy Sci 2020 Dec 23. Epub 2020 Dec 23.

Department of Animal Science, McGill University, Sainte-Anne-de-Bellevue, Quebec, H9X 3V9, Canada. Electronic address:

Although most farms in Canada still use tiestall housing for dairy cows, little information is available pertaining to cow comfort and behavior in such systems. Tiestalls are often criticized as they offer a reduced dynamic space to cows, thereby restricting their ability to move. The object of this study was to see if increasing the length of the tie chain provides cows with improved movement opportunities and to measure its effect on cows' rising and lying movements and behaviors. Two treatments were tested: the current recommendation of 1.00 m (recommended) and a longer chain of 1.40 m (long). Twenty-four cows (12/treatment) were blocked by parity number and lactation stage, then randomly allocated to a treatment and a stall within one of 2 rows in the research barn for 10 wk. Leg-mounted accelerometers were used to record lying behaviors and moments of transition between lying and standing positions for all cows. Cows were video-recorded for 24 h/wk using cameras positioned above the stall. The videos were used to evaluate the cows' rising and lying-down movements on wk 1, 2, 3, 6, 8, and 10. Six rising and 6 lying-down motions per cow per week were assessed by a trained observer to detect the presence of abnormal behaviors. Differences between and within treatments over time were analyzed in SAS (SAS Institute Inc., Cary, NC) using a mixed model with treatment, week, and block as fixed effects and with row and cow as random effects. Data from wk 1-3 were grouped together as the short-term effects, and those from wk 8-10 as the long-term effects. Week 6 was used as the mid-term assessment for analysis. Multiple comparisons between terms were accounted for using a Scheffé adjustment. Results indicate that duration of intention movements (exploratory head movements made by cows before lying down) is shorter in cows with longer chains (13.6 ± 1.03 s vs. 16.8 ± 1.01 s). It was also significantly shorter in the long term compared with the short term for both treatments (13.3 ± 0.92 s vs. 16.9 ± 0.81 s). These results suggest that increasing the chain length improves the cows' ease of movement and transitions, although all cows became more at ease in their surroundings with time. It may provide evidence of a potential way to improve the dynamic space provided to cows in tiestall systems, using a simple, affordable modification.
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http://dx.doi.org/10.3168/jds.2019-17666DOI Listing
December 2020

Making tiestalls more comfortable: III. Providing additional lateral space to improve the resting capacity and comfort of dairy cows.

J Dairy Sci 2020 Dec 23. Epub 2020 Dec 23.

Department of Animal Science, McGill University, Sainte-Anne-de-Bellevue, Quebec, H9X 3V9, Canada. Electronic address:

Dairy cows housed in tiestalls are restricted to one space; therefore, this space should be designed to accommodate all the activities cows need to perform. Lying is a very important behavior for dairy cows as well as a critical measure in the assessment of stall designs, to ensure that the cows' needs for resting space are met. The objective of this study was to determine if increasing tiestall width alters the lying behavior of lactating dairy cows. Two treatments were compared: the current recommendation (139 cm) and a double stall (284 cm). Sixteen cows were blocked by parity and lactation stage, then randomly allocated to a treatment and a stall within 1 of 2 rows in the research barn, for 6 wk. The average stall length was 188 cm. Leg-mounted accelerometers were used to record lying behaviors. Cows were video-recorded 24 h/wk using surveillance cameras positioned above the stalls. Video data from wk 1, 3, and 6 were extracted at a rate of 1 image/min and analyzed by a trained observer to assess the position and the location of the cow's body, head, and limbs during the lying hours. Lying behaviors and frequency of each position and location were analyzed in SAS (SAS Institute Inc., Cary, NC) using a mixed model in which treatment, block, and week were included as fixed factors, and cow and row as random factors. Multiple comparisons were adjusted using the Scheffé method. Results indicate that cows in double stalls fully extended their hindlimbs more often than single stall cows (21.7 vs. 7.6% of lying time). Cows in double stalls also intruded in the neighboring stalls with their hindlimbs less often (1.3 vs. 14.7% of lying time), instead positioning them inside their own stall more often (92.7 vs. 84.6% of lying time). Use of the second stall in the double stall group totaled 11.6, 5.1, 33.8, and 18.0% of lying time, respectively, for the head, front legs, hind legs, and body. Total lying time was not statistically different between double (716 min/d) and single stall (671 min/d) groups. Contacts with stall hardware during lying-down movements were also less frequent in double stalls (43.1 vs. 77.1% of lying events) compared with single stalls. These results suggest that dairy cows housed in double stalls modified their resting habits and used the extra space made available to them. Increasing stall width beyond the current recommendation is likely to benefit the cows by improving their ability to rest.
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http://dx.doi.org/10.3168/jds.2019-17667DOI Listing
December 2020

Making tiestalls more comfortable: I. Adjusting tie-rail height and forward position to improve dairy cows' ability to rise and lie down.

J Dairy Sci 2020 Dec 23. Epub 2020 Dec 23.

Department of Animal Science, McGill University, Sainte-Anne-de-Bellevue, Quebec, H9X 3V9, Canada. Electronic address:

The overall goal of the study was to develop new recommendations for tie-rail placement combining both vertical and horizontal positions to improve dairy cow welfare. Four treatments were tested: 2 new tie-rail positions that followed the natural neckline of cows when feeding and rising [neckline 1 (NL1), neckline 2 (NL2)], current recommendation (CR), and the average tie-rail position currently found on Quebec farms (current average on farm; CF). All other stall dimensions followed CR based on average cow size. Forty-eight cows blocked by parity and stage of lactation were randomly allocated to a treatment for 10 wk. Live scoring was performed weekly to evaluate injury, cow and stall cleanliness, and bedding quantity. Daily lying time, lying bout frequency, and lying bout duration were continuously recorded using leg-mounted accelerometers. Cows were recorded 1 d/wk by overhead cameras to evaluate lying down and rising events. Tie-rail placement did not affect cow and stall cleanliness, bedding quantity, and lying time. All tie-rail placements tested resulted in neck injuries with the position of neck injuries shifting based on the change in tie-rail placement: CR increased in proximal neck injuries (mean ± standard deviation, difference in injury score from baseline: +0.89 ± 0.153) compared with NL2 (+0.06 ± 0.153), but decreased in medial neck injuries (-0.11 ± 0.166) compared with NL2 (+0.78 ± 0.166) and NL1 (+0.53 ± 0.166). All treatments showed a decrease over time in average lying intention time (mean, difference between overall short- and long-term: -5.8 s/event), lying-down time (-1.1 s/event), contact with stall during lying (-32.5%), slipping during lying (-9.1%), backward movement on knees during rising (-10.9%), contact with tie-rail during rising (-14.3%), and overall abnormal rising (-15.6%) over time. Although lying and rising ability improved over time, abnormal lying and rising behaviors were still highly prevalent in the long term. Overall, our results show that dairy cows are limited in their ability to move within their environment without coming in contact with the stall confines (tie-rail and divider bars), warranting further research to determine alternatives to metal tie-rail bars, such as a flexible bar or chain, or provide fewer obstacles through the elimination of some stall hardware.
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http://dx.doi.org/10.3168/jds.2019-17665DOI Listing
December 2020

Dementia and Poor Continuity of Primary Care Delay Hospital Discharge in Older Adults: A Population-Based Study From 2001 to 2016.

J Am Med Dir Assoc 2020 Dec 23. Epub 2020 Dec 23.

Centre for Health Services and Policy Research, School of Population and Public Health, The University of British Columbia, Vancouver, British Columbia, Canada.

Objectives: Delayed discharge, remaining in acute care longer than medically necessary, reflects less than optimal use of hospital care resources and can have negative implications for patients. We studied (1) the change over time in delayed discharge in people with and without dementia, and (2) the association of delayed discharge with discharge destination and with the continuity of primary care prior to urgent admission.

Design: A retrospective population-based study.

Setting And Participants: Delayed discharge after urgent admission and length of delayed discharge were studied in all hospital users aged ≥70 years with at least 1 urgent admission in British Columbia, Canada, in years 2001/02, 2005/06, 2010/11, and 2015/16 (N = 276,299).

Methods: Linked administrative data provided by Population Data BC were analyzed using generalized estimating equations (GEE), logistic regression analysis, and negative binomial regression analyses.

Results: Delayed discharge increased among people with dementia and decreased among people without dementia, whereas the length of delay decreased among both. Dementia was the strongest predictor of delayed discharge [odds ratio 4.76; 95% confidence interval (CI) 4.59-4.93], whereas waiting for long-term care placement [incidence rate ratio (IRR) 1.56; 95% CI 1.50-1.62] and dementia (IRR 1.50; 95% CI 1.45-1.54) predicted a higher number of days of delay. Continuity and quantity of care with the same physician before urgent admission was associated with a decreased risk of delayed discharge, especially in people with dementia.

Conclusions And Implications: This study demonstrates the need for better system integration and patient-centered care especially for people with dementia. Population aging will likely increase the number of patients at risk of delayed discharge. Delayed discharge is associated with both the patient's complex needs and the inability of the system to meet these needs during and after urgent care. Sufficient investments are needed in both primary care and long-term care resources to reduce delayed discharges.
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http://dx.doi.org/10.1016/j.jamda.2020.11.030DOI Listing
December 2020

Implementing remote triage in large health systems: A qualitative evidence synthesis.

Res Nurs Health 2021 02 15;44(1):138-154. Epub 2020 Dec 15.

Durham Center of Innovation to Accelerate Discovery and Practice Transformation, Durham Veterans Affairs Health Care System, Durham, North Carolina, USA.

Remote triage (RT) allows interprofessional teams (e.g., nurses and physicians) to assess patients and make clinical decisions remotely. RT use has developed widespread interest due to the COVID-19 pandemic, and has future potential to address the needs of a rapidly aging population, improve access to care, facilitate interprofessional team care, and ensure appropriate use of resources. However, despite rapid and increasing interest in implementation of RT, there is little research concerning practices for successful implementation. We conducted a systematic review and qualitative evidence synthesis of practices that impact the implementation of RT for adults seeking clinical care advice. We searched MEDLINE®, EMBASE, and CINAHL from inception through July 2018. We included 32 studies in this review. Our review identified four themes impacting the implementation of RT: characteristics of staff who use RT, influence of RT on staff, considerations in selecting RT tools, and environmental and contextual factors impacting RT. The findings of our systemic review underscore the need for a careful consideration of (a) organizational and stakeholder buy-in before launch, (b) physical and psychological workplace environment, (c) staff training and ongoing support, and (d) optimal metrics to assess the effectiveness and efficiency of implementation. Our findings indicate that preimplementation planning, as well as evaluating RT by collecting data during and after implementation, is essential to ensuring successful implementation and continued adoption of RT in a health care system.
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http://dx.doi.org/10.1002/nur.22093DOI Listing
February 2021

An APEX2 proximity ligation method for mapping interactions with the nuclear lamina.

J Cell Biol 2021 Jan;220(1)

Carnegie Institution for Science, Department of Embryology, Baltimore, MD.

The nuclear lamina (NL) is a meshwork found beneath the inner nuclear membrane. The study of the NL is hindered by the insolubility of the meshwork and has driven the development of proximity ligation methods to identify the NL-associated/proximal proteins, RNA, and DNA. To simplify and improve temporal labeling, we fused APEX2 to the NL protein lamin-B1 to map proteins, RNA, and DNA. The identified NL-interacting/proximal RNAs show a long 3' UTR bias, a finding consistent with an observed bias toward longer 3' UTRs in genes deregulated in lamin-null cells. A C-rich motif was identified in these 3' UTR. Our APEX2-based proteomics identifies a C-rich motif binding regulatory protein that exhibits altered localization in lamin-null cells. Finally, we use APEX2 to map lamina-associated domains (LADs) during the cell cycle and uncover short, H3K27me3-rich variable LADs. Thus, the APEX2-based tools presented here permit identification of proteomes, transcriptomes, and genome elements associated with or proximal to the NL.
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http://dx.doi.org/10.1083/jcb.202002129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737704PMC
January 2021

Effects of habitat modifications on the movement behavior of animals: the case study of Fish Aggregating Devices (FADs) and tropical tunas.

Mov Ecol 2020 Nov 10;8(1):47. Epub 2020 Nov 10.

MARBEC, Univ Montpellier, CNRS, Ifremer, IRD, Sète, France.

Background: Aggregation sites represent important sources of environmental heterogeneity and can modify the movement behavior of animals. When these sites are artificially established through anthropogenic actions, the consequent alterations to animal movements may impact their ecology with potential implications for their fitness. Floating objects represent important sources of habitat heterogeneity for tropical tunas, beneath which these species naturally aggregate in large numbers. Man-made floating objects, called Fish Aggregating Devices (FAD), are used by fishers on a massive scale to facilitate fishing operations. In addition to the direct impacts that fishing with FADs has on tuna populations, assessing the effects of increasing the numbers of FADs on the ecology of tuna is key for generating sound management and conservation measures.

Methods: This study investigates the effects of increasing numbers of FADs (aggregation sites) on the movements of tunas, through the comparison of electronic tagging data recorded from 146 individuals tunas (yellowfin tuna, Thunnus albacares, and skipjack tuna, Katsuwonus pelamis) tagged in three instrumented anchored FAD arrays (Mauritius, Oahu-Hawaii and Maldives), that differed according to their distances among neighboring FADs. The effect of increasing inter-FAD distances is studied considering a set of indices (residence times at FADs and absence (travel) times between two visits at FADs) and their trends.

Results: When inter-FAD distances decrease, tuna visit more FADs (higher connectivity between FADs), spend less time travelling between FADs and more time associated with them. The trends observed for the absence (travel) times appear to be compatible with a random-search component in the movement behaviour of tunas. Conversely, FAD residence times showed opposite trends, which could be a result of social behavior and/or prey availability.

Conclusion: Our results provide the first evidence of changes in tuna associative behavior for increasing FAD densities. More generally, they highlight the need for comparing animal movements in heterogeneous habitats in order to improve understanding of the impacts of anthropogenic habitat modifications on the ecology of wild animals.
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http://dx.doi.org/10.1186/s40462-020-00230-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654007PMC
November 2020

Metabolic reprogramming of osteoclasts represents a therapeutic target during the treatment of osteoporosis.

Sci Rep 2020 12 3;10(1):21020. Epub 2020 Dec 3.

Department of Internal Medicine 3, Friedrich Alexander University of Erlangen-Nuremberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.

Osteoclasts are specialised bone resorbing cells that control both physiological and pathological bone turnover. Functional changes in the differentiation and activity of osteoclasts are accompanied by active metabolic reprogramming. However, the biological significance and the in vivo relevance of these events has remained unclear. Here we show that bone resorption of differentiated osteoclasts heavily relies on increased aerobic glycolysis and glycolysis-derived lactate production. While pharmacological inhibition of glycolysis did not affect osteoclast differentiation or viability, it efficiently blocked bone resorption in vitro and in vivo and consequently ameliorated ovariectomy-induced bone loss. Our experiments thus highlight the therapeutic potential of interfering with osteoclast-intrinsic metabolic pathways as possible strategy for the treatment of diseases characterized by accelerated bone loss.
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http://dx.doi.org/10.1038/s41598-020-77892-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713370PMC
December 2020

Examining the Impact of Fictional Life Story of Resident with Dementia on Staff Levels of Empathy, Self-confidence, Workload Burden, and Perception of Resident: A Cross-sectional Survey in Long-term Care Communities.

Clin Gerontol 2020 Dec 2:1-12. Epub 2020 Dec 2.

Psychology of Aging Unit, University of Liège , Liège, Belgium.

: Determine the impact of fictional life story on staff members levels of empathy, self-confidence, workload burden, and perception of resident before the implementation of care for new resident with dementia in long-term care community. : An online cross-sectional survey based on two fictive clinical vignettes was used: one vignette described a resident with typical medical information (e.g., level of autonomy, health status, medication …), while the other contained typical medical information and life story information. The two vignettes were visually similar. The order in which vignettes were read was counterbalanced. Staff members (n = 95) were asked to consider the care needed by these residents and to assess, with a visual analogue scale, the amount of useful information provided by vignettes, their self-confidence and level of empathy, their perception of the resident's level of sympathy, his dependence, and the associated workload. : After reading the vignette containing life story information, staff members considered that they had more useful information and empathy for the resident. They also felt more confident about the care. They perceived the resident as more sympathetic and less dependent, and the workload seemed lighter to them compared to the case described in the vignette that did not contain life story information. : This quantitative study shows, in clinical fictive situations, the positive impact of life story on staff members before care begins. : Results highlight the importance of considering life story early. Getting to know residents should be the first step of care.
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http://dx.doi.org/10.1080/07317115.2020.1845897DOI Listing
December 2020

Characterization of the Stereoselective P450 Enzyme BotCYP Enables the Biosynthesis of the Bottromycin Core Scaffold.

J Am Chem Soc 2020 12 28;142(49):20560-20565. Epub 2020 Nov 28.

Workgroup Structural Biology of Biosynthetic Enzymes, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, Campus Geb. E8.1, 66123 Saarbrücken, Germany.

Bottromycins are ribosomally synthesized and post-translationally modified peptide natural product antibiotics that are effective against high-priority human pathogens such as methicillin-resistant . The total synthesis of bottromycins involves at least 17 steps, with a poor overall yield. Here, we report the characterization of the cytochrome P450 enzyme BotCYP from a bottromycin biosynthetic gene cluster. We determined the structure of a close BotCYP homolog and used our data to conduct the first large-scale survey of P450 enzymes associated with RiPP biosynthetic gene clusters. We demonstrate that BotCYP converts a C-terminal thiazoline to a thiazole via an oxidative decarboxylation reaction and provides stereochemical resolution for the pathway. Our data enable the two-pot production of the bottromycin core scaffold and may allow the rapid generation of bottromycin analogues for compound development.
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http://dx.doi.org/10.1021/jacs.0c10361DOI Listing
December 2020

Women's Breast Cancer Knowledge and Health Communication in the United Arab Emirates.

Healthcare (Basel) 2020 Nov 18;8(4). Epub 2020 Nov 18.

College of Nursing, Ras Al Khaimah Medical & Health Sciences University, Al Qusaidat, UAE.

In the United Arab Emirates (UAE), women's participation in breast cancer screening is low, and women are commonly diagnosed in advanced stages. This study investigated women's attitudes towards breast cancer screening, their use of health services in the UAE emirate of Ras Al Khaimah, and their preferred medium for breast cancer information. In this qualitative study, six focus groups were conducted with Emirati ( = 28) and non-Emirati ( = 26) women as Ras Al Khaimah is a highly multi-cultural region. Women were separated into different age groups (25-34, 30-44, 44+) so as to obtain perspectives of young ( = 16), middle ( = 19), and older women ( = 19). The focus group transcripts were analysed using thematic analysis. Women recognised that any breast change should be checked by a doctor, and that women with symptoms or those at higher risk may need to have breast screening earlier than the recommended starting age. However, participants wanted more information from doctors or other health personnel. Women had observed breast cancer information and campaigns advertisements in multiple media but recommended greater use of social media and WhatsApp to disseminate information. Overall, women had positive attitudes towards breast cancer screening but wanted more breast cancer awareness campaigns year-round and better access to screening.
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http://dx.doi.org/10.3390/healthcare8040495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711768PMC
November 2020

NeoR, a near-infrared absorbing rhodopsin.

Nat Commun 2020 11 10;11(1):5682. Epub 2020 Nov 10.

Institute for Biology, Experimental Biophysics, Humboldt-Universität zu Berlin, 10115, Berlin, Germany.

The Rhizoclosmatium globosum genome encodes three rhodopsin-guanylyl cyclases (RGCs), which are predicted to facilitate visual orientation of the fungal zoospores. Here, we show that RGC1 and RGC2 function as light-activated cyclases only upon heterodimerization with RGC3 (NeoR). RGC1/2 utilize conventional green or blue-light-sensitive rhodopsins (λ = 550 and 480 nm, respectively), with short-lived signaling states, responsible for light-activation of the enzyme. The bistable NeoR is photoswitchable between a near-infrared-sensitive (NIR, λ = 690 nm) highly fluorescent state (Q = 0.2) and a UV-sensitive non-fluorescent state, thereby modulating the activity by NIR pre-illumination. No other rhodopsin has been reported so far to be functional as a heterooligomer, or as having such a long wavelength absorption or high fluorescence yield. Site-specific mutagenesis and hybrid quantum mechanics/molecular mechanics simulations support the idea that the unusual photochemical properties result from the rigidity of the retinal chromophore and a unique counterion triad composed of two glutamic and one aspartic acids. These findings substantially expand our understanding of the natural potential and limitations of spectral tuning in rhodopsin photoreceptors.
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http://dx.doi.org/10.1038/s41467-020-19375-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655827PMC
November 2020