Cost-sparing effect of twice-weekly targeted endurance training in type 2 diabetics: a one-year controlled randomized trial

OBJECTIVE: We evaluated the effects of targeted, moderate endurance training on healthcare cost, body composition and fitness in type 2 diabetes patients routinely followed within the French healthcare system. DESIGN AND METHODS: A total of 25 type 2 diabetic patients was randomly assigned to one of two groups: 13 underwent a training programme (eight sessions, followed by training twice a week for 30-45 minutes at home at the level of the ventilatory threshold [V(T)]); and 12 received their usual routine treatment. Both groups were followed for one year to evaluate healthcare costs, exercise effectiveness and a six-minute walking test. RESULTS: The training prevented loss of maximum aerobic capacity, which decreased slightly in the untrained group (P=0.014), and resulted in a higher maximum power output (P=0.041) and six-minute walking distance (P=0.020). The Voorrips activity score correlated with both V(O2max) (r=0.422, P<0.05) and six-minute walking distance (r=0.446, P<0.05). Changes in V(O2max) were negatively correlated with changes in body weight (r=0.608, P<0.01). Training decreased the insulin-resistance index (HOMA-IR) by 26% (P<0.05). Changes in percentages of fat were correlated to changes in waist circumference (r=0.436, P<0.05). The total healthcare cost was reduced by 50% in the trained group (euro 1.65+/-1 per day versus euro 3.00+/-1.47 per day in the untrained group; P<0.02) due to fewer hospitalizations (P=0.05) and less use of sulphonylureas (P<0.05). CONCLUSION: Endurance training at V(T) level prevented the decline in aerobic working capacity seen in untrained diabetics over the study period, and resulted in a marked reduction in healthcare costs due to less treatments and fewer hospitalizations.     

Expiratory-Synchronized Sleep in a Quadriplegic Patient Using Inspiratory Neck Muscles To Breathe

In a patient with C3 quadriplegia causing complete diaphragm paralysis who developed inspiratory neck muscles (INM) hypertrophy to sustain ventilation, spontaneous breathing deeply altered sleep architecture, relegating sleep to the expiratory phase of the ventilatory cycle. A polysomnographic recording performed during mechanical ventilation (without INM activity), showed that sleep was abnormal but unaffected by the respiratory cycle. During spontaneous breathing, the polygraphic recordings showed expiratory microsleep episodes, with inspiratory arousals synchronous to bursts of INM activity. This case report illustrates the powerful adaptability of the respiratory and sleep control systems to maintain each vital function.     

Identification of BRaf-Sparing Amino-Thienopyrimidines with Potent IRE1α Inhibitory Activity

Amino-quinazoline BRaf kinase inhibitor 2 was identified from a library screen as a modest inhibitor of the unfolded protein response (UPR) regulating potential anticancer target IRE1α. A combination of crystallographic and conformational considerations were used to guide structure-based attenuation of BRaf activity and optimization of IRE1α potency. Quinazoline 6-position modifications were found to provide up to 100-fold improvement in IRE1α cellular potency but were ineffective at reducing BRaf activity. A salt bridge contact with Glu651 in IRE1α was then targeted to build in selectivity over BRaf which instead possesses a histidine in this position (His539). Torsional angle analysis revealed that the quinazoline hinge binder core was ill-suited to accommodate the required conformation to effectively reach Glu651, prompting a change to the thienopyrimidine hinge binder. Resulting analogues such as 25 demonstrated good IRE1α cellular potency and imparted more than 1000-fold decrease in BRaf activity.     

Changes in Plant-Based Diet Indices and Subsequent Risk of Type 2 Diabetes in Women and Men: Three U.S. Prospective Cohorts

OBJECTIVEWe evaluated the associations between changes in plant-based diets and subsequent risk of type 2 diabetes.RESEARCH DESIGN AND METHODSWe prospectively followed 76,530 women in the Nurses’ Health Study (NHS) (1986–2012), 81,569 women in NHS II (1991–2017), and 34,468 men in the Health Professionals Follow-up Study (1986–2016). Adherence to plant-based diets was assessed every 4 years with the overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI). We used multivariable Cox proportional hazards models to estimate hazard ratios (HRs). We pooled results of the three cohorts using meta-analysis.RESULTSWe documented 12,627 cases of type 2 diabetes during 2,955,350 person-years of follow-up. After adjustment for initial BMI and initial and 4-year changes in alcohol intake, smoking, physical activity, and other factors, compared with participants whose indices remained relatively stable (±3%), participants with the largest decrease (>10%) in PDI and hPDI over 4 years had a 12–23% higher diabetes risk in the subsequent 4 years (pooled HR, PDI 1.12 [95% CI 1.05, 1.20], hPDI 1.23 [1.16, 1.31]). Each 10% increment in PDI and hPDI over 4 years was associated with a 7–9% lower risk (PDI 0.93 [0.91, 0.95], hPDI 0.91 [0.87, 0.95]). Changes in uPDI were not associated with diabetes risk. Weight changes accounted for 6.0–35.6% of the associations between changes in PDI and hPDI and diabetes risk.CONCLUSIONSImproving adherence to overall and healthful plant-based diets was associated with a lower risk of type 2 diabetes, whereas decreased adherence to such diets was associated with a higher risk.     

Improving diagnosis accuracy of brain volume abnormalities during childhood with an automated MP2RAGE-based MRI brain segmentation

Background and purposeIt can be challenging to depict brain volume abnormalities in the pediatric population on magnetic resonance imaging (MRI). The aim of the study was to evaluate the inter-radiologist reliability in brain MRI interpretation, including brain volume assessment and the efficiency of an automated brain segmentation.Materials and methodsWe performed a single-center prospective study including 44 patients aged six months to five years recruited from the University Hospital, having a 1.5 T brain MRI using a MP2RAGE sequence. All MRI were randomly and blindly reviewed by one junior and two senior pediatric radiologists. Inter-observer agreements were assessed using Fleiss’ kappa coefficient. Brain volumetry (total intracranial volume (TIV), brain parenchyma, and cerebrospinal fluid volumes) was estimated using the MorphoBox prototype. Clinical head circumference (HC) and z scores were reported. A Pearson correlation coefficient was calculated between brain volumes with HC.ResultsTwenty-four brain MRI examinations were normal and twenty were pathological. Brain volume abnormalities were poorly detected by junior and senior radiologists: sensitivities 16.67% [confidence interval 4.7–44.8], 33.33% [13–60] and 30.7% [12–58] and specificities 93.75% [79–98], 84.38% [68–93] and 77% [60–88], respectively. Brain volume apart, interobserver kappa coefficients were 0.93 between junior and seniors as well as between seniors. Brain volumes were significantly correlated with HC (P < 0.0001). In patients with normal MRI, brain parenchyma volumes increased regularly with age. Low brain volume was easier to identify with automated quantification.ConclusionBrain volume was poorly appreciated by radiologists. The fully automated brain segmentation used can provide quantitative data to better diagnose, describe, and follow-up brain volume abnormalities.     

Effects of mild chronic cerebral hypoperfusion and early amyloid pathology on spatial learning and the cellular innate immune response in mice

Understanding the contribution of cerebrovascular factors in the progression of cognitive decline in Alzheimer's disease (AD) is a key step for the development of preventive therapies. Among these factors, chronic cerebral hypoperfusion is an early component of AD pathogenesis that can predict the progression from mild cognitive impairment to AD. Here, we investigated the effects of a protocol of mild chronic cerebral hypoperfusion in the APPswe/PS1 transgenic mouse model of AD. We observed that the permanent occlusion of the right common carotid artery induced spatial learning impairments in young APPswe/PS1 mice, but not in their wild type littermates. Furthermore, the extent of learning deficits strongly correlated with the number of cortical β-amyloid plaques, with the mobilization of monocytes into the blood and with the number of bone marrow-derived microglia in the brain. These results indicate that a mild reduction of cerebral blood flow can selectively induce cognitive deficits at an early stage of amyloid pathology, eliciting a cellular innate immune response, even without causing neuronal death.     

Theoretical study of the flow rate toward the right heart territory in case of total occlusion of the right coronary artery

In this work, patients with severe coronary disease and chronic occlusion of the right coronary artery (RCA) are studied. In this clinical situation, the collateral circulation is an important factor in the preservation of the myocardium until reperfusion of the area at risk. An accurate estimation of collateral flow is crucial in surgical bypass planning as it can influence the outcome of a given treatment for a given patient. The evaluation of collateral flow is frequently achieved using an index (CFI, Collateral Flow Index) based on pressure measurements.Using a model of the coronary circulation based on hydraulic/electric analogy, we demonstrate, through theoretical simulations, that a wide range of fractional collateral flow values can be obtained for any given distal pressure difference depending on the values of the capillary and collateral resistances.     

Real-time modulation of visual feedback on human full-body movements in a virtual mirror: development and proof-of-concept

Background

Virtual reality (VR) provides interactive multimodal sensory stimuli and biofeedback, and can be a powerful tool for physical and cognitive rehabilitation. However, existing systems have generally not implemented realistic full-body avatars and/or a scaling of visual movement feedback. We developed a “virtual mirror” that displays a realistic full-body avatar that responds to full-body movements in all movement planes in real-time, and that allows for the scaling of visual feedback on movements in real-time. The primary objective of this proof-of-concept study was to assess the ability of healthy subjects to detect scaled feedback on trunk flexion movements.

Methods

The “virtual mirror” was developed by integrating motion capture, virtual reality and projection systems. A protocol was developed to provide both augmented and reduced feedback on trunk flexion movements while sitting and standing. The task required reliance on both visual and proprioceptive feedback. The ability to detect scaled feedback was assessed in healthy subjects (n = 10) using a two-alternative forced choice paradigm. Additionally, immersion in the VR environment and task adherence (flexion angles, velocity, and fluency) were assessed.

Results

The ability to detect scaled feedback could be modelled using a sigmoid curve with a high goodness of fit (R² range 89-98%). The point of subjective equivalence was not significantly different from 0 (i.e. not shifted), indicating an unbiased perception. The just noticeable difference was 0.035 ± 0.007, indicating that subjects were able to discriminate different scaling levels consistently. VR immersion was reported to be good, despite some perceived delays between movements and VR projections. Movement kinematic analysis confirmed task adherence.

Conclusions

The new “virtual mirror” extends existing VR systems for motor and pain rehabilitation by enabling the use of realistic full-body avatars and scaled feedback. Proof-of-concept was demonstrated for the assessment of body perception during active movement in healthy controls. The next step will be to apply this system to assessment of body perception disturbances in patients with chronic pain.