Diabetes and other vascular risk factors in association with the risk of lower extremity amputation in chronic limb-threatening ischemia: a prospective cohort study

BACKGROUND: Patients with diabetes are at increased risk of developing chronic limb-threatening ischemia (CLTI) due to peripheral arterial disease, and this often results in lower extremity amputation (LEA). Little is known of the interaction between diabetes and other vascular risk factors in affecting the risk of CLTI. METHODS: We investigated the association of diabetes, and its interaction with hypertension, body mass index (BMI) and smoking, with the risk of LEA due to CLTI in the population-based Singapore Chinese Health Study. Participants were interviewed at recruitment (1993-1998) and 656 incident LEA cases were identified via linkage with nationwide hospital database through 2017. Multivariate-adjusted Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% CIs for the associations. RESULTS: The HR (95% CI) for LEA risk was 13.41 (11.38-15.79) in participants with diabetes compared to their counterparts without diabetes, and the risk increased in a stepwise manner with duration of diabetes (P for trend < 0.0001). Hypertension and increased BMI independently increased LEA risk in those without diabetes but did not increase the risk in those with diabetes (P for interaction with diabetes ≤ 0.0006). Conversely, current smoking conferred a risk increment of about 40% regardless of diabetes status. CONCLUSIONS: Although diabetes conferred more than tenfold increase in risk of LEA, hypertension and increased BMI did not further increase LEA risk among those with diabetes, suggesting a common mechanistic pathway for these risk factors. In contrast, smoking may act via an alternative pathway and thus confer additional risk regardless of diabetes status

Human hippocampal CA3 damage disrupts both recent and remote episodic memories

Neocortical-hippocampal interactions support new episodic (event) memories, but there is conflicting evidence about the dependence of remote episodic memories on the hippocampus. In line with systems consolidation and computational theories of episodic memory, evidence from model organisms suggests that the cornu ammonis 3 (CA3) hippocampal subfield supports recent, but not remote, episodic retrieval. In this study, we demonstrated that recent and remote memories were susceptible to a loss of episodic detail in human participants with focal bilateral damage to CA3. Graph theoretic analyses of 7.0-Tesla resting-state fMRI data revealed that CA3 damage disrupted functional integration across the medial temporal lobe (MTL) subsystem of the default network. The loss of functional integration in MTL subsystem regions was predictive of autobiographical episodic retrieval performance. We conclude that human CA3 is necessary for the retrieval of episodic memories long after their initial acquisition and functional integration of the default network is important for autobiographical episodic memory performance

The predictive mirror: interactions of mirror and affordance processes during action observation

An important question for the study of social interactions is how the motor actions of others are represented. Research has demonstrated that simply watching someone perform an action activates a similar motor representation in oneself. Key issues include (1) the automaticity of such processes, and (2) the role object affordances play in establishing motor representations of others’ actions. Participants were asked to move a lever to the left or right to respond to the grip width of a hand moving across a workspace. Stimulus-response compatibility effects were modulated by two task-irrelevant aspects of the visual stimulus: the observed reach direction and the match between hand-grasp and the affordance evoked by an incidentally presented visual object. These findings demonstrate that the observation of another person’s actions automatically evokes sophisticated motor representations that reflect the relationship between actions and objects even when an action is not directed towards an object

Association of dual decline in cognition and gait speed with risk of dementia in older adults

Importance Dual decline in gait speed and cognition has been found to be associated with increased dementia risk in previous studies. However, it is unclear if risks are conferred by a decline in domain-specific cognition and gait.Objective To examine associations between dual decline in gait speed and cognition (ie, global, memory, processing speed, and verbal fluency) with risk of dementia.Design, Setting, and Participants This cohort study used data from older adults in Australia and the US who participated in a randomized clinical trial testing low-dose aspirin between 2010 and 2017. Eligible participants in the original trial were aged 70 years or older, or 65 years or older for US participants identifying as African American or Hispanic. Data analysis was performed between October 2020 and November 2021Exposures Gait speed, measured at 0, 2, 4, and 6 years and trial close-out in 2017. Cognitive measures included Modified Mini-Mental State examination (3MS) for global cognition, Hopkins Verbal Learning Test-Revised (HVLT-R) for memory, Symbol Digit Modalities (SDMT) for processing speed, and Controlled Oral Word Association Test (COWAT-F) for verbal fluency, assessed at years 0, 1, 3, 5, and close-out. Participants were classified into 4 groups: dual decline in gait and cognition, gait decline only, cognitive decline only, and nondecliners. Cognitive decline was defined as membership of the lowest tertile of annual change. Gait decline was defined as a decline in gait speed of 0.05 m/s or greater per year across the study.Main Outcomes and Measures Dementia (using Diagnostic and Statistical Manual of Mental Disorders [Fourth Edition] criteria) was adjudicated by an expert panel using cognitive tests, functional status, and clinical records. Cox proportional hazard models were used to estimate risk of dementia adjusting for covariates, with death as competing risk.Results Of 19 114 randomized participants, 16 855 (88.2%) had longitudinal gait and cognitive data for inclusion in this study (mean [SD] age, 75.0 [4.4] years; 9435 women [56.0%], 7558 participants [44.8%] with 12 or more years of education). Compared with nondecliners, risk of dementia was highest in the gait plus HVLT-R decliners (hazard ratio [HR], 24.7; 95% CI, 16.3-37.3), followed by the gait plus 3MS (HR, 22.2; 95% CI, 15.0-32.9), gait plus COWAT-F (HR, 4.7; 95% CI, 3.5-6.3), and gait plus SDMT (HR, 4.3; 95% CI, 3.2-5.8) groups. Dual decliners had a higher risk of dementia than those with either gait or cognitive decline alone for 3MS and HVLT-R.Conclusions and Relevance Of domains examined, the combination of decline in gait speed with memory had the strongest association with dementia risk. These findings support the inclusion of gait speed in dementia risk screening assessments

Super-resolution microscopy reveals coupling between mammalian centriole subdistal appendages and distal appendages

Copyright © 2020 Chong et al. Subdistal appendages (sDAPs) are centriolar elements that are observed proximal to the distal appendages (DAPs) in vertebrates. Despite the obvious presence of sDAPs, structural and functional understanding of them remains elusive. Here, by combining super-resolved localization analysis and CRISPR-Cas9 genetic perturbation, we find that although DAPs and sDAPs are primarily responsible for distinct functions in ciliogenesis and microtubule anchoring, respectively, the presence of one element actually affects the positioning of the other. Specifically, we find dual layers of both ODF2 and CEP89, where their localizations are differentially regulated by DAP and sDAP integrity. DAP depletion relaxes longitudinal occupancy of sDAP protein ninein to cover the DAP region, implying a role of DAPs in sDAP positioning. Removing sDAPs alter the distal border of centrosomal g-tubulins, illustrating a new role of sDAPs. Together, our results provide an architectural framework for sDAPs that sheds light on functional understanding, surprisingly revealing coupling between DAPs and sDAPs.Ministry of Science and Technology, Taiwan (107-2112-M-001-037, 107-2313-B-001-009, 108-2313-B-010-001, 108-2628-B-010-007, 108-2638-B-010-001 -MY2); Academia Sinica (2317-1040300); National Institutes of Health (GM088253)

Holographic renormalization and supersymmetry

Holographic renormalization is a systematic procedure for regulating divergences in observables in asymptotically locally AdS spacetimes. For dual boundary field theories which are supersymmetric it is natural to ask whether this defines a supersymmetric renormalization scheme. Recent results in localization have brought this question into sharp focus: rigid supersymmetry on a curved boundary requires specific geometric structures, and general arguments imply that BPS observables, such as the partition function, are invariant under certain deformations of these structures. One can then ask if the dual holographic observables are similarly invariant. We study this question in minimal N = 2 gauged supergravity in four and five dimensions. In four dimensions we show that holographic renormalization precisely reproduces the expected field theory results. In five dimensions we find that no choice of standard holographic counterterms is compatible with supersymmetry, which leads us to introduce novel finite boundary terms. For a class of solutions satisfying certain topological assumptions we provide some independent tests of these new boundary terms, in particular showing that they reproduce the expected VEVs of conserved charges.Comment: 70 pages; corrected typo

Intelligent Insect–Computer Hybrid Robot: Installing Innate Obstacle Negotiation and Onboard Human Detection onto Cyborg Insect

Developing small mobile robots for Urban Search and Rescue (USAR) is a major challenge due to constraints in size and power required to perform vital functions such as obstacle navigation, victim detection, and wireless communication. Drawing upon the idea that insects’ locomotion can be controlled, what if we further utilize the insects’ intrinsic ability to avoid obstacles? Herein, a cockroach hybrid robot (≈ 1.5 cm height, 5.7 cm length) that implements the abovementioned functions is developed. It is tested in an arena with randomly placed obstacles, and a motion capture system is used to track the insect's position among the untracked obstacles. A navigation algorithm that uses an inertial measurement unit (IMU) is developed to heuristically predict the insect's situation and stimulate the insect to escape nearby obstacles. The utilization of insect's intrinsic locomotor ability and low-powered IMU reduces the onboard power load, allowing the addition of a human-detecting function. An image classification model enables the use of an onboard low-resolution infrared camera for human detection. Consequently, a single hybrid robot is established that includes locomotion control, autonomous navigation in obstructed areas, onboard human detection, and wireless communication, representing a significant step toward real USAR application

Gestational diabetes mellitus and retinal microvasculature.

BACKGROUND: Small-vessel dysfunction may be an important consequence of chronic hyperglycemia. We examined the association between gestational diabetes mellitus (GDM), a state of transient hyperglycemia during pregnancy, and retinal microvascular changes in pregnant women at 26-28 weeks of pregnancy. METHODS: A total of 1136 pregnant women with singleton pregnancies were recruited during their first trimester at two major Singapore maternity hospitals in an on-going birth cohort study. Participants underwent an oral glucose tolerance test and retinal imaging at 26-28 weeks gestation (n = 542). We used the 1999 World Health Organization (WHO) criteria to define GDM: ≥7.0 mmol/L for fasting glucose and/or ≥7.8 mmol/L for 2-h post-glucose. Retinal microvasculature was measured using computer software (Singapore I Vessel Analyzer, SIVA version 3.0, Singapore Eye Research Institute, Singapore) from the retinal photographs. RESULTS: In a multiple linear regression model adjusting for age, ethnicity and maternal education, mothers with GDM had narrower arteriolar caliber (-1.6 μm; 95% Confidence Interval [CI]: -3.1 μm, -0.2 μm), reduced arteriolar fractal dimension (-0.01 Df; 95% CI: -0.02 Df, -0.001 Df;), and larger arteriolar branching angle (1.8°; 95% CI: 0.3°, 3.3°) than mothers without GDM. After further adjusting for traditional risks of GDM, arteriolar branching angle remained significantly larger in mothers with GDM than those without GDM (2.0°; 95% CI: 0.5°, 3.6°). CONCLUSIONS: GDM was associated with a series of retinal arteriolar abnormalities, including narrower caliber, reduced fractal dimension and larger branching angle, suggesting that transient hyperglycemia during pregnancy may cause small-vessel dysfunction

Super-resolution architecture of mammalian centriole distal appendages reveals distinct blade and matrix functional components

Copyright © The Author(s) 2018. Distal appendages (DAPs) are nanoscale, pinwheel-like structures protruding from the distal end of the centriole that mediate membrane docking during ciliogenesis, marking the cilia base around the ciliary gate. Here we determine a super-resolved multiplex of 16 centriole-distal-end components. Surprisingly, rather than pinwheels, intact DAPs exhibit a cone-shaped architecture with components filling the space between each pinwheel blade, a new structural element we term the distal appendage matrix (DAM). Specifically, CEP83, CEP89, SCLT1, and CEP164 form the backbone of pinwheel blades, with CEP83 confined at the root and CEP164 extending to the tip near the membrane-docking site. By contrast, FBF1 marks the distal end of the DAM near the ciliary membrane. Strikingly, unlike CEP164, which is essential for ciliogenesis, FBF1 is required for ciliary gating of transmembrane proteins, revealing DAPs as an essential component of the ciliary gate. Our findings redefine both the structure and function of DAPs.Ministry of Science and Technology, Taiwan (Grant Number 103-2112-M-001-039-MY3); Academia Sinica Career Development Award, Academia Sinica Nano Program; University of Alabama at Birmingham (UAB) Hepato/Renal Fibrocystic Diseases Core Center (HRFDCC) Pilot Award (NIH 5P30DK074038-09); NIH grant GM088253, American Cancer Society grant RSG-14-153-01-CCG; Geoffrey Beene Cancer Research Center grant

A systematic review of musculoskeletal disorders among school teachers

<p>Abstract</p> <p>Background</p> <p>Musculoskeletal disorders (MSD) represent one of the most common and most expensive occupational health problems in both developed and developing countries. School teachers represent an occupational group among which there appears to be a high prevalence of MSD. Given that causes of MSD have been described as multi-factorial and prevalence rates vary between body sites and location of study, the objective of this systematic review was to investigate the prevalence and risk factors for MSD among teaching staff.</p> <p>Methods</p> <p>The study involved an extensive search of MEDLINE and EMBASE databases in 2011. All studies which reported on the prevalence and/or risk factors for MSD in the teaching profession were initially selected for inclusion. Reference lists of articles identified in the original search were then examined for additional publications. Of the 80 articles initially located, a final group of 33 met the inclusion criteria and were examined in detail.</p> <p>Results</p> <p>This review suggests that the prevalence of self-reported MSD among school teachers ranges between 39% and 95%. The most prevalent body sites appear to be the back, neck and upper limbs. Nursery school teachers appear to be more likely to report suffering from low back pain. Factors such as gender, age, length of employment and awkward posture have been associated with higher MSD prevalence rates.</p> <p>Conclusion</p> <p>Overall, this study suggests that school teachers are at a high risk of MSD. Further research, preferably longitudinal, is required to more thoroughly investigate the issue of MSD among teachers, with a greater emphasis on the possible wider use of ergonomic principles. This would represent a major step forward in the prevention of MSD among teachers, especially if easy to implement control measures could be recommended.</p