rispevek se osredotoča na preučitev razmerja med dnevniki iskanj uporabnikov po spletnem slovarju in korpusno pogostostjo besed. Študijo so spodbudila razmišljanja, ki so se porajala pri rednem ...slovarskem delu in jih lahko strnemo v vprašanje: kako ohranjati na korpusu temelječ slovar aktualen? Bi morala biti naslednja beseda, ki jo uvrstimo v slovar, tista, ki sledi zadnji uslovarjeni besedi na frekvenčnem seznamu besed iz korpusa? Ali bi morala biti to beseda, ki jo uporabniki najpogosteje neuspešno iščejo v slovarju? Da bi prišli do ustreznih kriterijev, so avtorji analizirali dnevnike iskanj uporabnikov danskega slovarja v obdobju od 2009 do 2012 in seznam najpogosteje iskanih besed primerjali z njihovo pogostostjo v korpusu. S proučitvijo iskalnih navad uporabnikov so avtorji želeli priti do odgovorov na sledeča vprašanja: Ali so v slovarju besede, ki jih uporabniki nikoli ne iščejo? Če je odgovor da, ali lahko na podlagi njihove pogostosti v korpusu opazimo kakšne smiselne vzorce – gre za besede iste besedne vrste, so besede zelo pogoste ali zelo redke, se pojavljajo v določenem frekvenčnem območju? Ugotovitev prispevka je, da je pogostost v korpusu dober kriterij za 20.000 najpogostejših iztočnic, medtem ko je treba pri manj pogostih besedah dodati še druge metode, med katerimi je tudi pregled iskanj uporabnikov, nadvse pomembna pa je tudi presoja leksikografov.
Abstract
Background and Aims
Patients with some chronic liver diseases have increased risk of diabetes. Whether this is also the case for patients with autoimmune liver diseases is unknown. The study ...aimed to calculate risk and worldwide prevalence of diabetes in patients with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).
Methods
We performed a case–control study using data from the United Kingdom Biobank (UKB) and compared frequency of type 1 diabetes (T1D) and type 2 diabetes (T2D) in AIH and PBC with age‐, sex‐, BMI‐ and ethnicity‐matched controls. Next, we performed a systematic review and proportional meta‐analysis searching PubMed, Embase, Cochrane Library and Web of Science (inception to 1 May 2022 AIH; 20 August 2022 PBC; 11 November 2022 PSC). The pooled prevalence of diabetes was calculated using an inverse method random effects model.
Results
Three hundred twenty‐eight AIH patients and 345 PBC patients were identified in UKB and risk of T1D and T2D significantly increased compared with matched controls. Our systematic search identified 6914 records including the UKB study. Of these, 77 studies were eligible for inclusion comprising 36 467, 39 924 and 4877 individuals with AIH, PBC and PSC, respectively. The pooled prevalence of T1D was 3.8% (2.6%–5.7%), 1.7% (0.9%–3.1%), 3.1% (1.9%–4.8%) and of T2D 14.8% (11.1%–19.5%), 18.1% (14.6%–22.2%), 6.3% (2.8%–13.3%) in patients with AIH, PBC and PSC, respectively.
Conclusions
Patients with autoimmune liver diseases have increased risk of diabetes. Increased awareness of diabetes risk in patients with autoimmune liver diseases is warranted.
Work related upper body musculoskeletal symptoms and disorders constitute a major problem for operators of heavy machinery. Steering input devices mediate risk factors of upper body musculoskeletal ...disorders. Little research has been conducted to compare the multiple commercially available steering input devices in a multi-faceted approach. The present study evaluated five commonly used steering input devices (conventional steering wheel, fast steering wheel, miniature steering wheel, first-order joystick and second-order joystick) in terms of muscle activity, upper body kinematics and steering performance during heavy machine simulator driving. Fifteen healthy males novice to operation of heavy machinery completed five laps on a simulated track with each steering input device. Results showed a generally lower muscle activity when using the joysticks. The conventional and fast steering wheel increased mean wrist and shoulder flexion/extension angles and participants spent more time in wrist flexion/extension angles corresponding to moderate and poor comfort levels. An increased elbow protonation angle was found for the three steering wheels compared to the joysticks. The conventional steering wheel showed slowest track completion time and was subjectively ranked worst. The first-order joystick was ranked highest but also showed the highest amount of steering reversal rates, posing a risk of increased repetitiveness. Overall, the second-order joystick is considered superior ergonomically compared to the other steering input devices evaluated. However, all evaluated steering input devices exceeded muscle activity and/or joint angle recommendations.
Relevance to the industry: Compared to steering wheels, joystick steering showed reduced muscular activity and less awkward joint postures, suggesting a reduced risk of developing musculoskeletal disorders in the long term. However, the results warrant efforts to further develop joystick steering resulting in a reduction of exposure level beyond the existing solutions.
•Steering wheel manipulation required higher muscle activity compared to joysticks.•Joystick steering resulted in less forearm pronation compared to steering wheels.•All evaluated steering input devices exceed joint angle recommendations.•Joystick steering (1st and 2nd order) is ergonomically superior to steering wheels.•Conventional steering wheel operations resulted in slowest speed and path following.
The nanoscopic organization and regulation of individual molecular components in presynaptic varicosities of neurons releasing modulatory volume neurotransmitters like dopamine (DA) remain largely ...elusive. Here we show, by application of several super-resolution microscopy techniques to cultured neurons and mouse striatal slices, that the DA transporter (DAT), a key protein in varicosities of dopaminergic neurons, exists in the membrane in dynamic equilibrium between an inward-facing nanodomain-localized and outward-facing unclustered configuration. The balance between these configurations is inversely regulated by excitatory drive and DA D2 autoreceptor activation in a manner dependent on Ca2+ influx via N-type voltage-gated Ca2+ channels. The DAT nanodomains contain tens of transporters molecules and overlap with nanodomains of PIP2 (phosphatidylinositol-4,5-bisphosphate) but show little overlap with D2 autoreceptor, syntaxin-1, and clathrin nanodomains. The data reveal a mechanism for rapid alterations of nanoscopic DAT distribution and show a striking link of this to the conformational state of the transporter.
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•The dopamine transporter (DAT) is localized to PIP2-enriched nanodomains•Nanoclustered DAT is inward facing, and unclustered DAT is outward facing•Excitatory input disperses DAT from nanodomains in a Ca2+-dependent manner•In contrast, dopamine D2 receptor activity promotes DAT nanodomain localization
Lycas et al. use super-resolution microscopy to investigate nanoscale regulation of the dopamine transporter (DAT) in the membrane of presynaptic release sites. The results show conformation-dependent localization of DAT to PIP2-enriched nanodomains and that this localization is inversely regulated by excitatory input and dopamine D2 autoreceptor activity in a Ca2+-dependent manner.
We hypothesised that in acute high-risk surgical patients, a lower intraoperative peripheral perfusion index (PPI) would indicate a higher risk of postoperative complications and mortality.
This ...retrospective observational study included 1338 acute high-risk surgical patients from November 2017 until October 2018 at two University Hospitals in Denmark. Intraoperative PPI was the primary exposure variable and the primary outcome was severe postoperative complications defined as a Clavien–Dindo Class ≥III or death, within 30 days.
intraoperative PPI was associated with severe postoperative complications or death: odds ratio (OR) 1.12 (95% confidence interval CI 1.05–1.19; P<0.001), with an association of intraoperative mean PPI ≤0.5 and PPI ≤1.5 with the primary outcome: OR 1.79 (95% CI 1.09–2.91; P=0.02) and OR 1.65 (95% CI 1.20–2.27; P=0.002), respectively. Each 15-min increase in intraoperative time spend with low PPI was associated with the primary outcome (per 15 min with PPI ≤0.5: OR 1.11 (95% CI 1.05–1.17; P<0.001) and with PPI ≤1.5: OR 1.06 (95% CI 1.02–1.09; P=0.002)). Thirty-day mortality in patients with PPI ≤0.5 was 19% vs 10% for PPI >0.5, P=0.003. If PPI was ≤1.5, 30-day mortality was 16% vs 8% in patients with a PPI >1.5 (P<0.001). In contrast, intraoperative mean MAP ≤65 mm Hg was not significantly associated with severe postoperative complications or death (OR 1.21 95% CI 0.92–1.58; P=0.2).
Low intraoperative PPI was associated with severe postoperative complications or death in acute high-risk surgical patients. To guide intraoperative haemodynamic management, the PPI should be further investigated.
Background
Preoperative resuscitation strategies in patients with hip fracture (HF) are lacking. We aimed to investigate fluid‐responsiveness, peripheral perfusion index (PPI) and blood volume ...(BV)‐status in patients with HF undergoing resuscitation in the preoperative phase.
Methods
In a prospective observational study, we evaluated preoperative fluid‐responsiveness, indices of perfusion and BV before and after lumbar epidural analgesia in 50 patients with HF shortly after admittance.
Results
Initially, 18 (36%) patients were fluid‐responsive (≥10% increased SV in response to 250 ml fluid bolus) and 13 (26%) presented hypovolaemia (deviation of measured BV from estimated BV ≤ 0.9). According to fluid‐responsiveness, no difference in absolute values of cardiac index (CI) (2.7 L 2.1–3.3 vs. 2.8 L 2.3–3.4, p = .5) was seen, but cardiac output (CO) rose significantly in the hypovolaemic patients: 9% 5–18 vs. 1% −3–7, p = .004. After epidural analgesia, 26 (52%) patients were again fluid‐responsive and 15 (30%) were hypovolaemic. CI was now significantly lower in fluid‐responsive patients (2.2 L 1.7–2.7 vs. 2.9 L 2.3–3.5, p = .001). Prior to epidural analgesia, no significant trend towards hypovolaemic patients having lower indices of perfusion was seen. After epidural analgesia, more patients with hypovolaemia presented with PPI≤1.5 (8 (53%) vs. 3 (9%), p = .001) and absolute values of PPI were also significantly lower if IBV was low (1.4 0.9–3.2 vs. 3.2 2.4–4.8, p = .01). PPI correlated with hypovolaemia after epidural analgesia (rho 0.4 0.1–0.7, p = .007).
Conclusions
Preoperative fluid‐responsivity in HF patients might be attributable to elements of hypovolaemia and sympathetic compensatory ability conjointly, confounding the use of SV‐guided resuscitation. PPI could be associated with BV, which may support clinicians during perioperative haemodynamic optimisation.
Autoimmune liver diseases and diabetes Jensen, Anne-Sofie H; Ytting, Henriette; Winther-Sørensen, Marie ...
European journal of gastroenterology & hepatology,
09/2023, Letnik:
35, Številka:
9
Journal Article
Recenzirano
Autoimmune liver diseases include autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. They are chronic, heterogenous diseases affecting the liver which is a key ...metabolic organ that ensures glucose homeostasis. It is well known that patients with other chronic liver diseases such as cirrhosis and nonalcoholic fatty liver disease (NAFLD) display glucose disturbances like insulin resistance and have an increased risk of diabetes. Previous evidence on glucose disturbances in patients with autoimmune liver disease is scarce but does point towards a potentially increased risk of type 1 diabetes and type 2 diabetes. The underlying mechanisms are unknown but may reflect genetic predisposition, concurrent NAFLD and or cirrhosis development, and treatment (steroid) related impairment of glucose homeostasis. Therefore, increased awareness and surveillance of diabetes development in patients with autoimmune liver disease may be important. Overall, detection and treatment of diabetes generally follow the usual diabetes guidelines; however, in patients with advanced liver cirrhosis, HbA1c may not be a reliable marker of average glucose levels, and treatment with insulin is generally recommended. In addition, it has recently been suggested that sodium-glucose cotransporter 2 inhibitors may be beneficial in treating refractory ascites. Further research on diabetes risk in autoimmune liver disease is warranted.
Glucagon receptor agonism is currently explored for the treatment of obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). The metabolic effects of glucagon receptor agonism ...may in part be mediated by increases in circulating levels of Fibroblast Growth Factor 21 (FGF21) and Growth Differentiation Factor 15 (GDF15). The effect of glucagon agonism on FGF21 and GDF15 levels remains uncertain, especially in the context of elevated insulin levels commonly observed in metabolic diseases.
We investigated the effect of a single bolus of glucagon and a continuous infusion of glucagon on plasma concentrations of FGF21 and GDF15 in conditions of endogenous low or high insulin levels. The studies included individuals with overweight with and without MASLD, healthy controls (CON) and individuals with type 1 diabetes (T1D). The direct effect of glucagon on FGF21 and GDF15 was evaluated using our in-house developed isolated perfused mouse liver model.
FGF21 and GDF15 correlated with plasma levels of insulin, but not glucagon, and their secretion was highly increased in MASLD compared with CON and T1D. Furthermore, FGF21 levels in individuals with overweight with or without MASLD did not increase after glucagon stimulation when insulin levels were kept constant. FGF21 and GDF15 levels were unaffected by direct stimulation with glucagon in the isolated perfused mouse liver.
The glucagon-induced secretion of FGF21 and GDF15 is augmented in MASLD and may depend on insulin. Thus, glucagon receptor agonism may augment its metabolic benefits in patients with MASLD through enhanced secretion of FGF21 and GDF15.
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•FGF21 and GDF15 were highly increased in MASLD following glucagon stimulation.•Plasma FGF21 and GDF15 levels correlated with insulin, but not glucagon.•FGF21 was unaffected by glucagon stimulation when insulin levels were constant.•No direct effect of glucagon on FGF21 and GDF15 secretion•The increase of FGF21 and GDF15 by glucagon in MASLD may depend on insulin.
Background
The effects of vasoconstriction on cardiac stroke volume (SV) and indices of peripheral and intestinal perfusion are insufficiently described.
Methods
In a non‐randomized clinical study, ...30 patients undergoing elective rectal surgery were exposed to modulation of preload. The primary endpoint was intestinal perfusion (flux), measured by single‐point laser Doppler flowmetry. Secondary endpoints were central cardiovascular variables obtained by the LiDCO rapid monitor, the peripheral perfusion index (PPI) derived from the pulse oximetry signal and muscle (StO2) and cerebral oxygenation (ScO2) determined by near‐infrared spectroscopy.
Results
For the whole cohort (n = 30), administration of Phenylephrine during HUT induced a median IQR increase in SV by 22% 14–41, p = .003 and in mean arterial pressure (MAP) by 54% 31–62, p < .001, with no change in PPI, StO2 and ScO2 or flux. In patients who were preload dependent during HUT (stroke volume variation; SSV >10%; n = 23), administration of phenylephrine increased SV by 29% 12–43, p = .01 and MAP by 54% 33–63, p < .001, followed by an increase in intestinal perfusion flux by 60% 15–289, p = .05, while PPI, StO2 and ScO2 remained unchanged. For non‐preload dependent patients (SSV <10%; n = 7), no changes in hemodynamic indices were seen besides an increase in MAP by 54% 33–58, p = .002.
Conclusion
The reflection of vasoconstrictive modulation of preload in systemic cardiovascular variables and indices of perfusion was dependent on preload responsiveness. Administration of phenylephrine to increase preload did not appear to compromise organ perfusion.
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