Fibroblast growth factor 21 inversely correlates with survival in elderly population - the results of the Polsenior2 study.

Fibroblast growth factor 21 (FGF21) is a liver-secreted hormone involved in the regulation of lipid, glucose, and energy metabolism. Its serum concentration increases with age but also is higher in numerous diseases. FGF21 is being investigated for biomarker properties and as a potential therapeutic target. The present study aimed to assess the prognostic value of FGF21 in an older population-based cohort, the PolSenior2 study participants. In the sub-analysis of 3512 individuals, aged 60 and older, stratified according to FGF21 into tertiles, the survival estimate was worse in participants with middle and high levels compared to the lowest tertile. These results were consistent with univariable Cox regression analysis, in which participants in the middle and the high FGF21 tertiles after adjustment for age had 1.43-fold (HR, 1.31; 95% CI, 1.05 - 1.62) and 2.56-fold (HR, 1.94; 95% CI, 1.59 - 2.37) higher risk for mortality, respectively, compared with those in the lowest tertile. In multivariable Cox regression analysis, the highest levels of FGF21 were associated with increased mortality (HR 1.53; 95% CI, 1.22 - 1.92) independently of co-morbidities and blood parameters. These results indicate that higher serum FGF21 concentration is an independent predictor of all-cause mortality in the general population of older adults.

Simultaneous manipulation of iron(II) spin crossover and LIESST behaviour using pressure, temperature and light.

Spin crossover (SCO) and light-induced excited spin state trapping (LIESST) effects were studied using high pressure X-ray diffraction at cryogenic temperatures on a single crystal of the {[FeII(pyrazole)4]2[NbIV(CN)8]·4H2O}n (FeNb) coordination polymer. The studied compound does not show SCO or LIESST at ambient pressure, but these effects can be enforced by a mechanical stimulus. The obtained results demonstrate the manipulation of the spin state via the appropriate combination of multiple stimuli simultaneously.

Prevalence and risk factors of untreated thyroid dysfunctions in the older Caucasian adults: Results of PolSenior 2 survey.

INTRODUCTION: To determine the prevalence of treated and untreated thyroid dysfunction and to identify factors associated with increased risk of undiagnosed thyroid dysfunction in older adults. METHODS: The population of 5987 community-dwelling Polish Caucasian seniors aged 60 years and above who participated in the PolSenior 2 study (2018-2019). Population-based cross-sectional multidisciplinary study in design. Data from structured questionnaires, geriatric tests, and scales were obtained from all study participants who underwent anthropometric and blood pressure measurements during three home visits. Assessment of thyroid function was based on TSH serum measurements. RESULTS: The prevalence of thyroid dysfunction in the Polish population aged 60 years or above was estimated at 15.5% (21.5% in women and 7.2% in men), with 3.2% of undiagnosed individuals among them. The prevalence of hypothyroidism and hyperthyroidism in the studied group was 13.9% (19.4% in women and 6.3% in men) and 1.6% (2.1% in women and 0.9% in men) respectively, untreated hypothyroidism was revealed in 21.9% (in 160 out of 732 subjects) and untreated hyperthyroidism in 34.2% of subjects (in 41 out of 120 participants). In multiple regression analysis independent risk factors for thyroid disorders being untreated were older age (> 75 years), male sex, a low education level (primary or lower), and low utilization of medical services. CONCLUSIONS: One-fifth of Polish Caucasian seniors with hypothyroidism and one-third with hyperthyroidism are untreated. Older, poorly educated and rarely utilizing medical services seniors, especially men, are more frequently untreated for thyroid dysfunction and some of them do not benefit from contemporary achievements in medicine.

Antithymocyte Globulin as Second-Line Therapy in Graves Orbitopathy-Preliminary Results From a Prospective Single-Center Study.

Objective: Management of Graves' orbitopathy remains a challenge. Our previous case report has shown promising results for rabbit antithymocyte globulin (rATG) in the treatment of Graves' orbitopathy. Design: We present the response of 7 individuals with active moderate-to-severe steroid-resistant Graves' orbitopathy to rATG, representing preliminary results from a prospective single-center study. Methods: rATG was administered intravenously at a dose of 0.8-1.0 mg/kg daily (cumulative dose of 150-200 mg). The primary outcome measures at weeks 24 and 48 were ≥2-point reduction in Clinical Activity Score from baseline, a proptosis response, a diplopia response, and improvement of distant best-corrected visual acuity and mean retinal sensitivity. Key secondary outcomes included stabilization of ganglion cell complex thickness, a decrease of retinal nerve fiber layer in OCT, and a reduction in CD4/CD8 ratio and TRAb at 48 weeks. Results: An improvement in clinical activity score was observed in all patients, with disease inactivation in 3 cases. Proptosis reduction equal to or greater than 2 mm was noted for 8 of 10 eyes. Diplopia improved in three of 6 patients. There was an improvement in best-corrected visual acuity (from 0.69 to 0.78) and mean retinal sensitivity (from 20.8 to 23.5 dB). In addition, there was a long-lasting improvement in CD4/CD8 ratio in 6 patients. Two patients experienced adverse events (influenza and serum sickness). Conclusion: rATG therapy offers a long-lasting improvement in moderate-to-severe steroid-resistant Graves' orbitopathy with improvement in functional vision (reduction of diplopia, improvement of visual acuity, retinal sensitivity, and VEP pattern). The therapy is well-tolerated. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05199103.

Identical anomalous Raman relaxation exponent in a family of single ion magnets: towards reliable Raman relaxation determination?

Propeller-like lanthanide complexes with suitable chiral ligand scaffolds are highly desired as they combine chirality with possible magnetic bistability. However, the library of relevant chiral lanthanide-based molecules is quite limited. Herein we present the preparation, structures, magnetic behavior as well as EPR studies of a series of propeller-shaped lanthanide Single Ion Magnets (SIMs). Coordination of the smallest helicene-type molecule 1,10-phenanthroline-N,N'-dioxide (phendo) to LnIII ions results in the formation of homoleptic complexes [LnIII(phendo)4](NO3)3·xMeOH (Ln = Gd, Er, Yb) Gd, Er and Yb, where four phendos encircle the metal center equatorially in a four-bladed propeller fashion. The magnetization dynamics in these systems is studied by magnetic measurements and EPR spectroscopy for non-diluted as well as solid state dilutions of Er and Yb in a diamagnetic [YIII(phendo)4](NO3)3·xMeOH (Y) matrix. Careful analysis of the slow magnetic relaxation in the diluted samples can be described by a combination of Raman and Orbach relaxation mechanisms. The most important finding concerns the identical power law τ≈T-3 describing the anomalous Raman relaxation for all three reported compounds diluted in the Y matrix. This identical power law strongly suggests that the exponent of the Raman relaxation process in the series of solid-state diluted isostructural compounds is practically independent of the metal ion (as long as the molar mass changes are negligible) and highlights a possible experimental strategy towards reliable Raman relaxation determination.

Magnetization Dynamics and Coherent Spin Manipulation of a Propeller Gd(III) Complex with the Smallest Helicene Ligand.

A homoleptic gadolinium(III) complex with the smallest helicene-type ligand, 1,10-phenanthroline-N,N'-dioxide (phendo) [Gd(phendo)4](NO3)3·xMeOH (phendo = 1,10-phenanthroline-N,N'-dioxide, MeOH = methanol), shows slow relaxation of the magnetization characteristic for Single Ion Magnets (SIM), despite negligible magnetic anisotropy, confirmed by ab initio calculations. Solid state dilution magnetic and EPR studies reveal that the magnetization dynamics of the [Gd(phendo)4]3+ cation is controlled mainly by a Raman process. Pulsed EPR experiments demonstrate long phase memory times (up to 2.7 µs at 5 K), enabling the detection of Rabi oscillations at 20 K, which confirms coherent control of its spin state.

Evaluation of metformin therapy using controlled attenuation parameter and transient elastography in patients with non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is among the most common causes of liver disease worldwide. There is growing evidence on pathogenesis and pathophysiology of NAFLD. However, there is still no universally accepted pharmacotherapy protocol. METHODS: The study was conducted on 42 patients with NAFLD. They were randomized to dietary treatment alone (n = 21) or to diet and metformin therapy (n = 21). Liver ultrasonography, controlled attenuation parameter (CAP), liver stiffness (LS), complete blood count, anthropometric and biochemical parameters were obtained before treatment (baseline), and after 3 and 5 months of the therapy. RESULTS: Patients treated with diet and metformin exhibited significantly decreased CAP values at 3 and 5 months of the therapy compared to baseline (319 dB/m vs. 285 dB/m; p < 0.05; 319 dB/m vs. 295 dB/m; p < 0.05 respectively). Five months of diet and the metformin therapy resulted in significant reduction of LS value (6.2 kPa vs. 5.2 kPa; p < 0.05), while patients treated with diet alone had no significant changes in liver CAP and LS measurements. CONCLUSIONS: Metformin therapy combined with dietary treatment seems to be effective for the reduction of hepatic steatosis and fibrosis. However, considering limitations of the study and inconsistent results of previous investigations in this area, there is a need for further research on metformin efficacy in this group of patients.

Cross-linking of cyanide magnetic coordination polymers by rational insertion of formate, cyanide or azide.

Carefully selected molecular bridging ligands formate, cyanide and azide, that are known to transmit strong magnetic interactions, have been successfully inserted into the {[MnII(H2O)2]2[NbIV(CN)8]·4H2O}n (Mn2Nb) ferrimagnetic parent framework, resulting in the additional molecular bridging of the two MnII centres in three new coordination polymers: {(NH4)[(H2O)MnII-(µ-HCOO)-MnII(H2O)][NbIV(CN)8]·3H2O}nMn2NbHCOO, {(NH4)[(NH3)MnII-(µ-CN)-MnII(H2O)][NbIV(CN)8]·2H2O}nMn2NbCN and {(NH4)[(H2O)MnII-(µ-N3)-MnII(H2O)][NbIV(CN)8]·3H2O}nMn2NbN3. The extra bridging ligands cross-linking the two MnII centers strongly influence the long-range ferrimagnetic order of the NbIV-CN-MnII parent framework by introducing competing antiferromagnetic interactions. The values of the JMnMn constants were obtained by fitting the magnetic properties of the MoIV congeners {(NH4)[(H2O)MnII-(µ-HCOO)-MnII(H2O)][MoIV(CN)8]·3H2O}nMn2MoHCOO, {(NH4)[(NH3)MnII-(µ-CN)-MnII(H2O)][MoIV(CN)8]·2H2O}nMn2MoCN and {(NH4)[(H2O)MnII-(µ-N3)-MnII(H2O)][MoIV(CN)8]·3H2O}nMn2MoN3, where the paramagnetic NbIV was substituted by the diamagnetic MoIV, thus disabling the long-range magnetic ordering of the CN-framework. Our strategy demonstrates how chemists can control the magnetic behavior of molecular magnets by subtle and rational structural modification based on chemical knowledge.

Cyanide vs. azide "magnetic arm wrestling": MnII-NbIV and MnII-MoIV magnetic coordination polymers with mixed bridging.

Two magnetic coordination polymers with mixed cyanide-azide bridging based on octacyanoniobate(iv) and octacyanomolybdate(iv) are reported: {(NH4)[(H2O)MnII-(µ-N3)-MnII(H2O)][MIV(CN)8]·3H2O}n Mn2MN3 (M = Nb or Mo). Cyanide ligands form the 3-D framework of Mn2MN3, while azide ligands connect two MnII centres together. Both CN- and N3- are known in magnetochemistry for their marked magnetic coupling abilities which in the case of Mn2NbN3 lead to competitive antiferromagnetic interactions within the NbIV-CN-MnII and MnII-N3-MnII structural motifs. This competition results in a peculiar magnetic behaviour consistent with a non-collinear magnetic structure.

[The role of adipokines and insulin resistance in the pathogenesis of nonalcoholic fatty liver disease]. / Rola adipokin i insulinoopornosci w patogenezie niealkoholowej stluszczeniowej choroby watroby.

Nonalcoholic fatty liver disease (NAFLD) develops in 17-33% of the population of developed countries. The incidence of NAFLD is constantly growing due to the increasing prevalence of obesity. It is estimated that one third of subjects with NAFLD suffer from nonalcoholic steatohepatitis (NASH) and 15% of them develop liver cirrhosis within a five-year period. In recent years this important complication of obesity became the subject of numerous studies. It, the pathogenesis of NAFLD is still unclear. A key role in the development of this disease was attributed to insulin resistance. Hormones and cytokines produced by adipose tissue called adipokines may be a link between obesity, insulin resistance, and NAFLD. However, it is well known that increased levels of adipokines such as TNF-alpha, IL-6, and resistin and a decreased level of adiponectin augment inflammation in the liver. Further studies are necessary to explain the roles of leptin, visfatin, retinol binding protein-4, omentin, and vaspin in the pathogenesis of NAFLD. The aim this paper is to introduce new areas of study on the pathogenesis of NAFLD.

Hemostatic effects of fenofibrate in patients with mixed dyslipidemia and impaired fasting glucose.

Our study aimed to compare the effect of fenofibrate on hemostasis between patients with isolated impaired fasting glucose (IFG) and isolated mixed dyslipidemia and to examine the action of this agent on glucose and lipid metabolism. Twenty-two IFG and 23 mixed dyslipidemic patients were treated for 90 days with micronized fenofibrate (267 mg/day) and were compared with 22 age-, sex- and weight-matched control subjects without lipid and glucose metabolism abnormalities. The lipid profile, fasting and 2-h post-glucose challenge glucose levels, HOMA and glycated hemoglobin as well as the plasma levels/activities of fibrinogen, factor VII and PAI-1 were determined at the beginning and after 30 and 90 days of treatment. Compared to the control subjects, mixed dyslipidemic and IFG patients exhibited increased plasma levels of fibrinogen and PAI-1 as well as increased factor VII activity. Fibrinogen, factor VII and PAI-1 were higher in mixed dyslipidemic than IFG subjects. Not only did fenofibrate improve plasma lipids, but it also increased glucose sensitivity and normalized the IFG- and mixed dyslipidemia-induced changes in coagulation and fibrinolysis. Our study shows that IFG is associated with abnormal hemostasis, which is disturbed to a lesser extent in IFG than in mixed dyslipidemia. Fenofibrate seems to produce a complex beneficial effect on hemostasis in this group of patients.