Human Physiology of Genetic Defects Causing Beta-cell Dysfunction

The last decade has revealed hundreds of genetic variants associated with type 2 diabetes, many especially with insulin secretion. However, the evidence for their single or combined effect on beta-cell function relies mostly on genetic association of the variants or genetic risk scores with simple traits, and few have been functionally fully characterized even in cell or animal models. Translating the measured traits into human physiology is not straightforward: none of the various indices for beta-cell function or insulin sensitivity recapitulates the dynamic interplay between glucose sensing, endogenous glucose production, insulin production and secretion, insulin clearance, insulin resistance-to name just a few factors. Because insulin sensitivity is a major determinant of physiological need of insulin, insulin secretion should be evaluated in parallel with insulin sensitivity. On the other hand, multiple physiological or pathogenic processes can either mask or unmask subtle defects in beta-cell function. Even in monogenic diabetes, a clearly pathogenic genetic variant can result in different phenotypic characteristics-or no phenotype at all. In this review, we evaluate the methods available for studying beta-cell function in humans, critically examine the evidence linking some identified variants to a specific beta-cell phenotype, and highlight areas requiring further study. (C) 2020 The Authors. Published by Elsevier Ltd.Peer reviewe

Wave conditions in the Baltic Proper and in the Gulf of Finland during windstorm Gudrun

International audienceWave conditions in the northern Baltic Proper during windstorm Erwin/Gudrun (January 2005) are analysed based on in situ measurements in three locations and output of operational wave models from the German Weather Forecast Service, the Danish Meteorological Institute and the Finnish Institute of Marine Research. The measured significant wave height reached 7.2 m in the northern Baltic Proper and 4.5 m in the Gulf of Finland. The roughest wave conditions, estimated from the comparison of the forecast and measured data, occurred remote from the sensors, off the coasts of Saaremaa and Latvia where the significant wave height was about 9.5 m. Peak periods exceeded 12 s in a large part of the northern Baltic Proper and in the central part of the Gulf of Finland

Implications of cellular agriculture for hospitality and tourism management research: sustainable development goal perspective.

The global agricultural sector is facing a disruption driven by economics, emerging technology, and environmental and personal well-being. In particular, advances in cellular biology, along with the emergence of novel production techniques such as precision fermentation, are making the mass-cultivation of alternative proteins in vitro for human consumption an economically plausible proposition. Along with technical and ethical questions, for example on the choice of growth medium or policy implications, the prospect of a decentralised, cultured protein supply chain opens up interesting avenues of future research for hospitality and tourism management. How will hospitality and tourism stakeholders react when new technologies give rise to food service and food tourism that is less reliant on conventional animal husbandry and where properties such as taste, texture, mouthfeel, or tolerability can be cultivated from the molecule-up? Using United Nations’ Sustainable Development Goals as a backdrop, this conceptual viewpoint article adopts an applied integrative review methodology to discuss megatrends driving the adoption of a cellular agriculture -based food production system, and puts forward an agenda for future research into cellular agriculture in the context of hospitality and tourism management

Biliary Anomalies in Patients With HNF1B Diabetes

Context: The clinical spectrum of organogenetic anomalies associated with HNF1B mutations is heterogeneous. Besides cystic kidney disease, diabetes, and various other manifestations, odd cases of mainly neonatal and posttransplantation cholestasis have been described. The biliary phenotype is incompletely defined. Objective: To systematically characterize HNF1B-related anomalies in the bile ducts by imaging with magnetic resonance imaging (MRI) or magnetic resonance cholangiopancreatography (MRCP). Setting and Patients: Fourteen patients with HNF1B mutations in the catchment area of the Helsinki University Hospital were evaluated with upper abdominal MRI and MRCP. Blood samples and clinical history provided supplemental data on the individual phenotype. Main Outcome Measure(s): Structural anomalies in the biliary system, medical history of cholestasis, other findings in abdominal organs, diabetes and antihyperglycemic treatment, hypomagnesemia, and hyperuricemia. Results: Structural anomalies of the bile ducts were found in seven of 14 patients (50%). Six patients had choledochal cysts, which are generally considered premalignant. Conclusions: Structural anomalies of the biliary system were common in HNF1B mutation carriers. The malignant potential of HNF1B-associated choledochal cysts warrants further studies.Peer reviewe

The influence of psychosocial factors at work and life style on health and work ability among professional workers

OBJECTIVES: The purpose of this article is to explore the associations of psychosocial factors at work, life style, and stressful life events on health and work ability among white-collar workers. METHODS: A cross-sectional survey was conducted among workers in commercial services (n = 1141). The main outcome variables were work ability, measured by the work ability index (WAI), and mental and physical health, measured by the Short-Form Health Survey (SF-12). Individual characteristics, psychosocial factors at work, stressful life events, and lifestyle factors were determined by a questionnaire. Maximum oxygen uptake, weight, height, and biceps strength were measured during a physical examination. RESULTS: Work ability of white-collar workers in commercial services industry was strongly associated with psychosocial factors at work such as teamwork, stress handling, and self-development and, to a lesser extent, with stressful life events, lack of physical activity, and obesity. Determinants of mental health were very similar to those of work ability, whereas physical health was influenced primarily by life style factors. With respect to work ability, the influence of unhealthy life style seems more important for older workers, than for their younger colleagues. CONCLUSION: Among white-collar workers mental and physical health were of equal importance to work ability, but only mental health and work ability shared the same determinants. The strong associations between psychosocial factors at work and mental health and work ability suggest that in this study population health promotion should address working conditions rather than individual life style factors

Transport dynamics in a complex coastal archipelago

The Archipelago Sea (in the Baltic Sea) is characterised by thousands of islands of various sizes and steep gradients of the bottom topography. Together with the much deeper Åland Sea, the Archipelago Sea acts as a pathway to the water exchange between the neighbouring basins, Baltic proper and Bothnian Sea. We studied circulation and water transports in the Archipelago Sea using a new configuration of the NEMO 3D hydrodynamic model that covers the Åland Sea–Archipelago Sea region with a horizontal resolution of around 500 m. The results show that currents are steered by the geometry of the islands and straits and the bottom topography. Currents are highest and strongly aligned in the narrow channels in the northern part of the area, with the directions alternating between south and north. In more open areas, the currents are weaker with wider directional distribution. During our study period of 2013–2017, southward currents were more frequent in the surface layer. In the bottom layer, in areas deeper than 25 m, northward currents dominated in the southern part of the Archipelago Sea, while in the northern part southward and northward currents were more evenly represented. Due to the variation in current directions, both northward and southward transports occur. During our study period, the net transport in the upper 20 m layer was southward. Below 20 m depth, the net transport was southward at the northern edge and northward at the southern edge of the Archipelago Sea. There were seasonal and inter-annual variations in the transport volumes and directions in the upper layer. Southward transport was usually largest in spring and summer months, and northward transport was largest in autumn and winter months. The transport dynamics in the Archipelago Sea show different variabilities in the north and south. A single transect cannot describe water transport through the whole area in all cases. Further studies on the water exchange processes between the Baltic proper and the Bothnian Sea through the Archipelago Sea would benefit from using a two-way nested model set-up for the region.</p

Systemic Safety in Ranibizumab-Treated Patients with Neovascular Age-Related Macular Degeneration : a Patient-Level Pooled Analysis

Topic: This study evaluated the cardiovascular/cerebrovascular safety profile of ranibizumab 0.5 mg versus sham \ub1 verteporfin in patients with neovascular age-related macular degeneration (nAMD). In addition, comparisons of ranibizumab 0.3 mg with sham and ranibizumab 0.5 mg to 0.3 mg were performed. Clinical Relevance: Intravitreal anti\u2013vascular endothelial growth factor (VEGF) agents carry potential increased systemic risks, including cardiovascular or cerebrovascular events. Pooled safety analyses allow better interpretation of safety outcomes seen in individual clinical trials, especially for less common events. To our knowledge, this is the largest patient-level pooled analysis of patients with nAMD treated with ranibizumab. Methods: Patient-level pooled analysis of data from 7 Genentech- and Novartis-sponsored phase II, III, and IV studies in nAMD that were completed by December 31, 2013. Pairwise comparisons (primary comparison: ranibizumab 0.5 mg [globally approved dose for nAMD] vs. sham or verteporfin) were performed using Cox proportional hazard regression (hazard ratios [HRs], 95% confidence intervals [CIs]) and rates per 100 patient-years. Standardized Medical Dictionary for Regulatory Activities queries (SMQs) and extended searches were used to identify relevant safety endpoints, including arterial thromboembolic events (ATEs), myocardial infarction (MI), stroke or transient ischemic attack (TIA), stroke (excluding TIA), vascular deaths, and major vascular events as defined by the Antiplatelet Trialists\u2019 Collaboration (APTC). Results: The HRs (95% CIs) for the primary comparison of ranibizumab 0.5 mg (n=480) versus sham or verteporfin (n=462) were 1.16 (0.72\u20131.88) for ATE, 1.33 (0.59\u20132.97) for MI, 1.43 (0.54\u20133.77) for stroke excluding TIA, 1.25 (0.61\u20132.55) for stroke or TIA, 0.57 (0.18\u20131.78) for vascular death, and 1.12 (0.64\u20131.98) for APTC events. Hazard ratio 95% CIs included 1, indicating no significant treatment differences, for all endpoints for comparison of ranibizumab 0.5 mg versus sham or verteporfin. Conclusions: The rates of cardiovascular and cerebrovascular events were low in these patients with nAMD and not clinically meaningfully different for patients treated with ranibizumab 0.5 mg versus sham or verteporfin, which supports the favorable benefit\u2013risk profile of ranibizumab in the patient population with nAMD. Pooling these studies allows an analysis with higher power and precision compared with individual study analyses

Study protocol: the effects of work-site exercise on the physical fitness and work-ability of older workers

BACKGROUND: Older workers have a higher rate and cost of injury than younger workers and with a rapidly ageing work force there is a need to identify strategies to address this problem. Older workers are less physically active and fit than younger workers and so have reduced work ability. The reduced work ability means they are more likely to be fatigued at work and so at greater risk of injury. Exercise could potentially assist this problem. Exercise training has been previously shown to improve fitness in older people however there has been no evaluation of workplace exercise program for older workers. We do not know if the programs are feasible and can improve the fitness and work ability of older workers. We have designed a randomised controlled trial to evaluate whether exercise improves fitness and perceived work-ability of older workers. METHODS/DESIGN: This paper describes the protocol for a trial examining the effects of a 12-week physical training program in workers over the age of 45. Participants will be randomized to an exercise or no-intervention control group. The primary outcomes are cardiorespiratory endurance, lifting capacity, upper and lower limb strength and perceived work-ability. DISCUSSION: This trial will test the feasibility of implementing a worksite-based exercise program as a means of improving the physical fitness and work-ability of older workers performing physically demanding work. If we demonstrate the feasibility of the program we will conduct a larger trial that additionally measures injury outcomes

In vitro cytotoxicity and surface topography evaluation of additive manufacturing titanium implant materials

Custom-designed patient-specific implants and reconstruction plates are to date commonly manufactured using two different additive manufacturing (AM) technologies: direct metal laser sintering (DMLS) and electron beam melting (EBM). The purpose of this investigation was to characterize the surface structure and to assess the cytotoxicity of titanium alloys processed using DMLS and EBM technologies as the existing information on these issues is scarce. "Processed" and "polished" DMLS and EBM disks were assessed. Microscopic examination revealed titanium alloy particles and surface flaws on the processed materials. These surface flaws were subsequently removed by polishing. Surface roughness of EBM processed titanium was higher than that of DMLS processed. The cytotoxicity results of the DMLS and EBM discs were compared with a "gold standard" commercially available titanium mandible reconstruction plate. The mean cell viability for all discs was 82.6% (range, 77.4 to 89.7) and 83.3% for the control reconstruction plate. The DMLS and EBM manufactured titanium plates were non-cytotoxic both in "processed" and in "polished" forms.Peer reviewe