Introduction.We have reported that beta cell-specific ablation of somatostatin receptor subtype 5 (SSTR5) using the CRE-Lox system results in early changes in the endocrine pancreas and autoimmune diabetes. The purpose of this study was to examine the effect of global ablation of SSTR5 on the endocrine pancreas, insulin secretion, and glucose tolerance in aging mice. Methods. Global SSTR5Ϫ/Ϫ mice were generated and genotypes were verified using Southern blot and RT-PCR. Glucose tolerance and in vivo insulin secretion in SSTR5Ϫ/Ϫ and WT mice were examined using intraperitoneal glucose tolerance test (IPGTT;1.2-2.0 mg/kg) at 3, 6, 12, 18, and 24 months of age (n ϭ 8 per group). Basal and glucosestimulated insulin secretion in vitro was studied using the isolated perfused mouse pancreas model at 3, 6, and 12 months. Pancreata were removed at 3 and 12 months of age and levels of the pancreasspecific transactivator PDX-1, proliferating cell nuclear antigen (PCNA), insulin, glucagon, somatostatin, and SSTR1 were studied using immunostaining. Results. Genotyping verified the absence of SSTR5 in SSTR5Ϫ/Ϫ mice. IPGTT demonstrated that SSTR5Ϫ/Ϫ mice had normal glucose tolerance and insulin response at 3 months; however, glucose intolerance and blunted insulin responses were found in 6 months and older SSTR5Ϫ/Ϫ mice compared with WT controls (P Ͻ 0.05). H&E study demonstrated normal islets at 3 months; however, a marked increase in islet size and number were seen in 12-month SSTR5Ϫ/Ϫ mice and was associated with a significant increase of both PDX-1 and PCNA staining. SSTR1 expression was significantly increased in islet at 3 months of age, but was absent in islets at 12 months of age, as was somatostatin staining in SSTR5Ϫ/Ϫ mouse. Conclusions. Global ablation of SSTR5 resulted in alterations in glucose and insulin homeostasis only in older mice (Ն6 months). Older SSTR5Ϫ/Ϫ mice had up regulation of PDX-1, PCNA, and marked islet proliferation, which coincided with the disappearance of SSTR1 expression and somatostatin staining in older mice. These results suggest that both SSTR5 and SSTR1 play a pivotal role in insulin secretion, glucose regulation, and islet cell proliferation in the aging mouse. Reduced Severity in a Mouse Model of Colitis with Angio-tensin Converting Enzyme Inhibition. A.
People with peripheral neuropathy (PN) are at risk of falling. Many people with PN have comorbid cognitive impairment, an independent risk factor of falls, which may further increase the risk of falling in people with PN. However, the negative synergic effect of those factors is yet to be reported. We investigated whether the presence of cognitive impairment exacerbates the risk of falls in people with PN by measuring gait variability during single-task walking and dual-task walking. Forty-four adults with PN were recruited. Based on the Montreal Cognitive Assessment (MoCA) scores, 19 and 25 subjects were cognitively impaired and intact, respectively. We measured coefficients of variation of gait speed, stride length, and stride time using validated body-worn sensors. During single-task walking, no between-group differences were observed (all p > 0.05). During dual-task walking, between-group differences were significant for gait variability for gait speed and stride length (51.4% and 71.1%, respectively; p = 0.014 and 0.011, respectively). MoCA scores were significantly correlated with gait variability for gait speed (r = 0.319, p = 0.035) and stride length (r = 0.367, p = 0.014) during dual-task walking. Our findings suggest that the presence of cognitive impairment exacerbates the risk of falls in people with PN.
Neuropathic individuals are at risk of falls, however potential impact of cognitive impairment in neuropathic individuals is not well-understood. Since cognitive impairment is considered an independent risk factor for falls, knowing its potential, additional impact may help better understand underlying mechanism of risk of falls in neuropathic individuals. We aimed to investigate stride-to-stride variability in neuropathic individuals with cognitive impairment (NP-Cog-Impaired) and without cognitive impairment (NP-Cog-Intact) during normal and dual-task walking. Neuropathic symptoms and cognitive status was measured using maximum vibration perception threshold (VPTmax) in the feet and the Montreal Cognitive Assessment (MoCA), respectively. We analyzed data from 19 NP-Cog-Impaired (8 men; 68.5±9.1 years; 29.0±6.2 kg/m2; VPTmax=27.2±12.1 volts; MoCA=19.6±2.4) and 25 NP-Cog-Intact (15 men; 66.5±9.1 years; 31.3±5.9 kg/m2; VPTmax=26.3±12.7 volts; MoCA=25.6±1.6). We collected movement data using five inertial sensors (LEGSysTM, BioSensics LLC, Watertown, MA) attached on the shanks, thighs and lower back. We used previously validated algorithm to calculate coefficient of variations (CV) of stride velocity and stride length. CV of stride velocity and stride length were significantly greater for the NP-Cog-Impaired group (11.07±5.22% and 7.31±3.20%, respectively) than for the NP-Cog-Intact group (7.31±3.20% and 4.81±2.80%, respectively) for dual-task walking but not for normal walking. Between normal and dual-task walking, CV of stride velocity and stride length increased 43.2% (significantly) and 46.4% (marginally), respectively, from normal walking to dual-task walking for the NP-Cog-Impaired group but not for the NP-Cog-Intact group. Results suggest that cognitive impairment may be an additional risk factor of falls in neuropathic individuals.
Frailty status is a well-known predictor of adverse health outcomes and functional performance. An assessment tool based on a wearable sensor was developed to quickly assess frailty using an upper extremity flexion and extension test. However, the current tool has relied on conventional frailty assessment to classify the frailty status of the participant. The aim of this study is to operationalize the frailty index based on wearable sensor to classify frailty status of older adults. 104 older adults were recruited for the study (age=78.6 ±9.7 years old). Participants were asked to perform a quick 20-second upper flexion and extension task while wearing a gyroscope on the wrist. A sensor-based frailty index (FI) was derived using parameters extracted from the sensor. Participants were also assessed using the Fried Phenotype Criteria (FC) and were classified into three groups: robust, pre-frail, and frail. Mean-shift clustering algorithm was used to operationalize the FI by identifying the cut-off point for each group. Grip strength and physical activity level were used as functional outcome measures. Regression analysis (r) was used to compare the correlation of the FC and FI with the identified metrics. Bivariate analysis show that grip strength was highly associated with the sensor-based frailty classification (r=-0.547) and FC (r =-0.503). The sensor-based classification was significantly associated with walking activity (r=-0.355). The results showed that the sensor-based frailty assessment tool could be used to quickly classify frailty status in older adults and eliminated the need for subjective and time-consuming evaluation.
Digital technologies have features that may attenuate the core benefits of industrial hubs. The assumption that geography via co-location facilitates technology spillover provides the basis for the policy design of industrial hubs. Yet, this goes against digital trends in global value chains which enable longer and more dispersed value chains by reducing the need for high levels of trust between entities. We explore the impact of one specific type of digital technology—blockchain—that fundamentally shifts the importance of geography for trade. We illustrate some of the problems with hubs using an extended discussion of multilateral trading rules. Finally, we close with a look at the sustainability angle and whether using a distributed architecture can promote the sustainability production with which hubs struggle.
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Successful outcomes for free tissue transfer are well-documented in pediatric patients but less so in infants. Challenges with infants are unique and include implications of prolonged anesthetic exposure. We present a 9-month-old female who underwent a free latissimus dorsi flap to reconstruct a congenital upper extremity lesion threatening limb development.
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