Strong Chiroptical Effects in the Absorption and Emission of Macrocycles Based on the 2,5-Diaminoterephthalate Minimal Fluorophore.

Chiral fluorescent macrocycles consisting of two to four units of dimethyl 2,5-diaminoterephthalate can be readily synthesized in a one-pot manner from inexpensive building blocks. Depending on the concentration, either a paracyclophane-like dimer with closely stacked benzene rings or a triangular trimer is the main product of the reaction. The macrocycles exhibit fluorescence in solution as well as in the solid state with maxima that are red-shifted with decreasing size of the macrocyclic ring and are observed at wavelengths from 590 (tetramer in solution) to 700 nm (dimer in the solid state). Chirality dictates the differential absorption and emission of circularly polarized light by these molecules. The ECD and CPL effects are particularly strong for the trimer, which is characterized by relatively large dissymmetry factors gabs =±2.8×10-3 at 531 nm and glum =±2.3×10-3 at 580 nm in n-hexane, being at the same time highly luminescent (Φfl =13.7 %). Despite the small chromophore, the circularly polarized brightness BCPL of 2.3 dm3 mol-1 cm-1 is comparable to values reported for other classes of established CPL emitters in the visible region, such as expanded helicenes or larger π-conjugated systems.

The Effects of Neuropeptide B on Proliferation and Differentiation of Porcine White Preadipocytes into Mature Adipocytes.

Neuropeptide B (NPB) affects energy homeostasis and metabolism by binding and activating NPBWR1 and NPBWR2 in humans and pigs. Recently, we reported that NPB promotes the adipogenesis of rat white and brown preadipocytes as well as 3T3-L1 cells. In the present study, we evaluated the effects of NPB on the proliferation and differentiation of white porcine preadipocytes into mature adipocytes. We identified the presence of NPB, NPBWR1, and NPBWR2 on the mRNA and protein levels in porcine white preadipocytes. During the differentiation process, NPB increased the mRNA expression of PPARγ, C/EBPß, C/EBPα, PPARγ, and C/EBPß protein production in porcine preadipocytes. Furthermore, NPB stimulated lipid accumulation in porcine preadipocytes. Moreover, NPB promoted the phosphorylation of the p38 kinase in porcine preadipocytes, but failed to induce ERK1/2 phosphorylation. NPB failed to stimulate the expression of C/EBPß in the presence of the p38 inhibitor. Taken together, we report that NPB promotes the differentiation of porcine preadipocytes via a p38-dependent mechanism.

Rapidly growing uterine myoma - should we be afraid of it?

During a year, myomas may undergo radical changes in their dimensions - from decreasing by 90% to growing by 200%. On average, myomas of the uterus increase in volume by 20-30% annually in the premenopausal period. On the other hand, myomas regress spontaneously in about 20% of women. After menopause uterine fibroids stabilize or regress. Every new or growing lesion of the uterus after menopause has to be diagnosed. There is no general definition of fast growing uterine myoma. The presence of fast growing uterine myoma, regardless of its definition, is associated with some clinical issues: it may become symptomatic (pain, bleeding, bulk symptoms), may be responsible for infertility, and a malignant process (leiomyosarcoma) may be present. Regardless of common belief, the risk of sarcoma is not related to the size of the uterus or its fast enlargement. The prevalence of sarcoma in myomas is 0.26%, and in rapidly growing myomas is 0.27%. Treatment should be individualized, selected for the age of the woman and her expectations (preservation of fertility, uterus), symptoms, size and localization of the myomas. The methods of surgical treatment of unsuspected "rapidly growing myomas" are the same as those of common uterine fibroids. Minimally invasive surgery is optimal, but a decision has to be made after evaluation of the risk factors of sarcoma.

Valsalva-derived Measures and Phenylephrine Test in Patients With Heart Failure With Reduced Ejection Fraction Receiving Comprehensive Neurohormonal Blockade Drug Therapy: A 5-year Event-free Survival Analysis.

BACKGROUND: To assess the relationships between Valsalva- and phenylephrine test-derived measures and outcome in patients with heart failure with reduced ejection fraction (HFrEF) receiving comprehensive neurohormonal blockade pharmacotherapy. METHODS AND RESULTS: Data from 56 patients with HFrEF (mean left ventricle ejection fraction of 32 ± 6%) subjected to Valsalva and phenylephrine tests were analyzed retrospectively. Baroreflex-related (Valsalva-ratio and blood pressure-RR interval slope from phase IV) and non-baroreflex-related measures (systolic blood pressure rise in phase IV [ΔSBPPHASE_IV], and pulse amplitude ratio [PAR]) were calculated from Valsalva. Short-term outcomes (HF-related hospitalization, implantable cardioverter-defibrillator shock or all-cause death within 24 months from examination) and long-term outcomes (implantable cardioverter-defibrillator shock or all-cause death within 60 months) were analyzed. The end point occurred in 16 and 18 patients, for the short- and long-term outcomes, respectively. A low ΔSBPPHASE_IV identified patients at risk in the long term, as evidenced by a low vs high ΔSBPPHASE_IV comparison (square-wave response patients assigned to low ΔSBPPHASE_IV group, P = .002), and Cox model (hazard ratio 0.91, 95% confidence interval 0.86-0.96, P < .001), and tended to identify patients at risk in the short term outcome (hazard ratio 0.95, 95% confidence interval 0.91-1.00, P = .055). There was a tendency toward a higher event-free survival in the low PAR group (low vs high PAR; hazard ratio 0.44, 95% CI 0.17-1.18, P = .104). CONCLUSIONS: Non-baroreflex-related measures obtained from Valsalva-namely, ΔSBPPHASE_IV and PAR-might carry prognostic value in patients with HFrEF receiving neurohormonal blockade pharmacotherapy.

Daily Treatment of Mice with Type 2 Diabetes with Adropin for Four Weeks Improves Glucolipid Profile, Reduces Hepatic Lipid Content and Restores Elevated Hepatic Enzymes in Serum.

Adropin is a peptide hormone encoded by Energy Homeostasis Associated gene. Adropin modulates energy homeostasis and metabolism of lipids and carbohydrates. There is growing evidence demonstrating that adropin enhances insulin sensitivity and lowers hyperlipidemia in obese mice. The aim of this study was to investigate the effects of daily administration of adropin for four weeks in mice with experimentally induced type 2 diabetes (T2D). Adropin improved glucose control without modulating insulin sensitivity. Adropin reduced body weight, size of adipocytes, blood levels of triacylglycerol and cholesterol in T2D mice. T2D mice treated with adropin had lower liver mass, reduced hepatic content of triacylglycerol and cholesterol. Furthermore, adropin attenuated elevated blood levels of hepatic enzymes (ALT, AST, GGT and ALP) in T2D mice. In T2D mice, adropin increased the circulating adiponectin level. Adropin had no effects on circulating insulin and glucagon levels and did not alter pancreatic islets morphology. These results suggest that adropin improves glucose control, lipid metabolism and liver functions in T2D. In conjunction with reduced lipid content in hepatocytes, these results render adropin as an interesting candidate in therapy of T2D.

Changes in metabolic and hormonal profiles during transition period in dairy cattle - the role of spexin.

BACKGROUND: This study aimed to evaluate spexin as a novel blood marker and to describe the relationship of this peptide with selected biochemical metabolites measured during the transition period in dairy cows. Additionally, mRNA expression of the spexin gene as well as spexin receptors - galanin receptor type 2 and galanin receptor type 3, was investigated in several bovine tissues. Blood samples were collected at weekly intervals starting at 21 days before the estimated parturition day until 21 days in milk to determine concentrations of spexin, nonesterified fatty acids, ß-hydroxybutyrate acid, total and active ghrelin, progesterone, glucose, insulin, IGF-I, triglycerides, cholesterol, leptin, corticosterone and 17-ß-estradiol as well as the activity of aspartate transaminase, alkaline phosphatase and gamma-glutamyl transferase. RESULTS: Spexin concentration decreased from 21 d before parturition to calving day and next it rose during the first 14 d of lactation. The lowest concentration of spexin was recorded on the calving day and it differed from the mean level of this peptide before parturition as well as postpartum. Moreover, differences were observed between mean spexin concentrations before and after calving. Spexin levels were moderately negatively correlated with NEFA (r = - 0.39) and total ghrelin contents (r = - 0.41), weakly correlated with BHBA (r = - 0.35) while they showed a moderate positive relationship with progesterone concentrations (r = 0.42). Moreover, we detected that mRNA expression of GALR2, GALR3 and SPX is present in various bovine tissues (kidney, bowel, rumen, spinal cord, lung, skeletal muscle, liver, heart, fat and spleen). CONCLUSION: A negative correlation between spexin concentration and NEFA, BHBA and total ghrelin contents as well as a positive relationship with levels of progesterone, metabolites and hormones, which are key players in the dairy cow transition period, may confirm an important function of this peptide in metabolism regulation. Thus measurement of spexin concentration could provide useful supplementary information for dairy cow herd health monitoring.

The Role of Neuropeptide B and Its Receptors in Controlling Appetite, Metabolism, and Energy Homeostasis.

Neuropeptide B (NPB) is a peptide hormone that was initially described in 2002. In humans, the biological effects of NPB depend on the activation of two G protein-coupled receptors, NPBWR1 (GPR7) and NPBWR2 (GPR8), and, in rodents, NPBWR1. NPB and its receptors are expressed in the central nervous system (CNS) and in peripheral tissues. NPB is also present in the circulation. In the CNS, NPB modulates appetite, reproduction, pain, anxiety, and emotions. In the peripheral tissues, NPB controls secretion of adrenal hormones, pancreatic beta cells, and various functions of adipose tissue. Experimental downregulation of either NPB or NPBWR1 leads to adiposity. Here, we review the literature with regard to NPB-dependent control of metabolism and energy homeostasis.

Pathophysiology of Advanced Heart Failure: What Knowledge Is Needed for Clinical Management?

Understanding of heart failure (HF) has evolved from a simple hemodynamic problem through a neurohormonally and proinflammatory-driven syndrome to a complex multiorgan dysfunction accompanied by inadequate energy handling. This article discusses the most important clinical aspects of advanced HF pathophysiology. It presents the concept of neurohormonal activation and its deleterious effect on cardiovascular system and reflex control. The current theories regarding the role of inflammation, cytokine activation, and myocardial remodeling in HF progression are presented. Advanced HF is a multiorgan syndrome with interplay between cardiovascular system and other organs. The role of iron deficiency is also discussed.

Adropin stimulates proliferation but suppresses differentiation in rat primary brown preadipocytes.

Adropin is a peptide hormone encoded by Energy Homeostasis Associated (Enho) gene. Adropin modulates glucose and lipid metabolism, and adiposity. Recently, we found that adropin suppresses differentiation of rodent white preadipocytes into mature fat cells. By contrast, the role of adropin in controlling brown adipogenesis is largely unknown. Therefore, in the present study we evaluated the effects of adropin on proliferation and differentiation of adipocyte precursor cells in rats. Brown adipocyte precursor cells were isolated from male Wistar rats. Cell replication was measured by BrdU incorporation. Gene expression was studied using real time PCR. Protein phosphorylation and production was assessed by Western blot. Lipid accumulation was evaluated by Oil Red O staining. Colorimetric kits were used to evaluate glycerol and free fatty acids release. We report here that adropin stimulates proliferation of brown preadipocytes. Moreover, in brown preadipocytes, adropin suppresses mRNA expression of adipogenic genes (C/ebpα, C/ebpß, Pgc1α, Pparγ and Prdm16) during differentiation process. In addition, adropin suppresses UCP1 protein production in brown adipocytes. Finally, adropin reduces intracellular lipid content in brown adipocytes. These results indicate that adropin stimulates proliferation of brown preadipocytes and suppresses their differentiation into mature adipocytes.

Chain length of dietary fatty acids determines gastrointestinal motility and visceromotor function in mice in a fatty acid binding protein 4-dependent manner.

PURPOSE: We hypothesize that different types of dietary fatty acids (FAs) affect gastrointestinal (GI) motility and visceromotor function and that this effect can be regulated by the fatty acid binding protein 4 (FABP4). METHODS: Mice were fed for 60 days with standard diet (STD), STD with 7% (by weight) coconut oil, rich in medium-chain FAs (MCFAs) (COCO), or with 7% evening primrose oil, rich in long-chain FAs (LCFAs) (EPO). In each group, half of the mice received FABP4 inhibitor, BMS309403 (1 mg/kg; i.p.) twice a week. Body weight (BW) and food intake were measured; well-established tests were performed to characterize the changes in GI motility and visceral pain. White adipose tissue and colonic samples were collected for cell culturing and molecular studies. RESULTS: COCO significantly increased GI transit, but not colonic motility. COCO and EPO delayed the onset of diarrhea, but none affected the effect of loperamide. EPO reduced BW and increased the visceromotor response (VMR) to colorectal distension (CRD). COCO and EPO reduced differentiation of preadipocytes. Treatment with BMS309403: (1) reversed the effects induced by COCO in physiological conditions and in mouse models of diarrhea; (2) prevented the effects of EPO on BW, VMR to CRD and castor oil-induced diarrhea; (3) affected proliferation of preadipocytes; (4) changed the expression of Fabp4 in colonic and adipocyte samples from COCO and EPO. CONCLUSION: Modifying dietary intake of MCFAs and LCFAs may be used to control GI motility or visceral pain and thus modulate the symptoms of functional GI disorders. The effect is dependent on the expression of FABP4.

Frailty and cognitive impairment are predictive of takotsubo syndrome following pacemaker implantation.

BACKGROUND: Pacemaker (PM) implantation may cause acute emotional distress leading to takotsubo syndrome (TTS). Frailty and cognitive impairment are known to influence outcomes after surgical procedures. It is unclear whether they may also predispose to TTS following PM implantation. METHODS: We identified nine cases (81 ± 6 years) of TTS following PM implantation that took place between 2013 and 2017 in one high volume implantation center. TTS was diagnosed based on typical echocardiographic appearance with resolution over time and (in cases where deemed necessary) normal coronary angiography. The TTS cases were compared with 30 consecutive cases of PM implantation (75 ± 9 years), which were not complicated by TTS (control group). Frailty was assessed using retrospective Risk Analysis Index (RAI-A). Pacing parameters were analyzed during PM implantation and after 1 month. RESULTS: Cognitive impairment was more prevalent (67% vs 10%, P = .0005), and RAI-A index was significantly higher in the TTS group compared to the control group (26 ± 13.7 vs 13.1 ± 9.8, P = .008). Perioperative right ventricular threshold was significantly higher in patients with TTS comparing to controls (0.99 ± 0.43 V vs 0.74 ± 0.20 V, P = .04). The magnitude of decrease in right ventricular threshold between implantation and 1 month follow-up was greater in TTS patients compared to controls (-0.41 ± 0.29 V vs -0.15 ± 0.38 V, P = .049). CONCLUSIONS: TTS is a rare complication of PM implantation. Patients with cognitive impairment and frailty are at risk of TTS. Right ventricular pacing threshold is acutely affected by TTS and improves over time.

Short-term administration of spexin in rats reduces obesity by affecting lipolysis and lipogenesis: An in vivo and in vitro study.

The present study aimed to characterize the role of spexin (SPX) in maintaining glucose and lipid homeostasis in vivo in rats with diet-induced obesity. The in vitro effect of spexin on metabolic and endocrine functions of adipocytes isolated from obese rats was also investigated. The in vivo experiment was conducted on rats with diet-induced obesity and administered with SPX for 7 days. Lipid and carbohydrate parameters, liver markers, and hormonal profile were measured. In in vitro studies, adipocytes isolated from obese rats were used. The effect of SPX on lipolysis, lipogenesis, and leptin secretion from fat cells was assessed. The results showed that short-term administration of SPX causes weight loss, increases insulin sensitivity, and improves the metabolic state of obese rats. The in vitro experiments showed that spexin and its receptors, namely galanin receptor 2 (GALR2) and galanin receptor 3 (GALR3), were expressed in various fat depots and in adipocytes from obese rats. We also found that the addition of spexin increased the basal and isoproterenol-stimulated lipolysis and reduced the basal and insulin-stimulated lipogenesis in adipocytes isolated from obese rats. Molecular analysis showed that SPX activated hormone-sensitive lipase (HSL) phosphorylation and upregulated perilipin and HSL mRNA expression. These results suggest that SPX regulates metabolism of obese rats by affecting lipolysis and lipogenesis in adipocytes. Moreover, the present study for the first time demonstrates that SPX modulates leptin synthesis and secretion from isolated adipocytes.

FGF-1 modulates pancreatic ß-cell functions/metabolism: An in vitro study.

Fibroblast growth factor 1 (FGF-1), also known as acidic fibroblast growth factor (aFGF), is a growth factor and signaling protein encoded by the Fgf1 gene. Previous studies have shown that FGF-1 may also participate in the regulation of glucose metabolism, both in healthy organisms and in pathological conditions such as diabetes. Because insulin the main regulator of glucose metabolism is secreted from pancreatic beta cells, we investigated whether FGF-1 directly affects the secretion of this hormone and regulates the metabolism of beta cells and isolated pancreatic islets. By using insulin-producing INS-1E cells and isolated pancreatic islets, we investigated the effect of FGF-1 on cell proliferation, viability, apoptosis, and insulin expression and secretion. Our study showed that FGF1 and fibroblast growth factor receptors (FgfRs: FgfR1, FgfR2, FgfR3, and FgfR4) are present on mRNA level in INS-1E cells and isolated rat pancreatic islets. We also proved that FGF1 stimulates the proliferation of INS-1E beta cells and enhances the viability of these cells and that of isolated pancreatic islet cells, and that ERK1/2 kinase is involved in the regulation of INS-1E cell proliferation. Moreover, we found that FGF1 can stimulate insulin secretion from both INS-1E cells and isolated rat pancreatic islets. Thus, the FGF1 peptide increases cell survival and decreases cell death. The obtained results indicate that FGF1 may play a role in controlling the physiology and metabolism of pancreatic beta cells as well as glycemia.

The assessment of quality of life and satisfaction with life of patients before and after surgery of an isolated apical defect using synthetic materials.

BACKGROUND: Pelvic floor static disorders constitute a significant clinical and social problem. The incidence of the problem increases with the age of female patients up to 80 years of age. Due to various methods of procedural treatment, eligibility for surgery should be carefully discussed with the patient. Ideally, the surgery should be effective and with the least possible number of complications. The objective of this study was to assess the quality of life of patients before and after the surgery of an isolated apical defect with the use of BSC mesh. METHODS: The study involved 60 patients who were diagnosed with pelvic floor static disorder on the basis of physical examination. Standardised questionnaires were used to assess the quality of life and satisfaction with life: the Perceived Quality of Life (P-QOL) and the Satisfaction With Life Scale (SWLS). RESULTS: The P-QOL results for each domain were higher in patients before surgery compared to the results obtained after the surgery. For almost all domains, the results obtained were statistically significant. The results obtained in the SWLS questionnaire in most answers also show that after the procedure there was an improvement in satisfaction with life in the examined female patients. CONCLUSION: In most patients, surgical treatment of an isolated apical defect using BSC mesh results in the subsidence of bothersome symptoms and improves the quality of life.

Phoenixin: More than Reproductive Peptide.

Phoenixin (PNX) neuropeptide is a cleaved product of the Smim20 protein. Its most common isoforms are the 14- and 20-amino acid peptides. The biological functions of PNX are mediated via the activation of the GPR173 receptor. PNX plays an important role in the central nervous system (CNS) and in the female reproductive system where it potentiates LH secretion and controls the estrus cycle. Moreover, it stimulates oocyte maturation and increases the number of ovulated oocytes. Nevertheless, PNX not only regulates the reproduction system but also exerts anxiolytic, anti-inflammatory, and cell-protective effects. Furthermore, it is involved in behavior, food intake, sensory perception, memory, and energy metabolism. Outside the CNS, PNX exerts its effects on the heart, ovaries, adipose tissue, and pancreatic islets. This review presents all the currently available studies demonstrating the pleiotropic effects of PNX.

Adropin as A Fat-Burning Hormone with Multiple Functions-Review of a Decade of Research.

Adropin is a unique hormone encoded by the energy homeostasis-associated (Enho) gene. Adropin is produced in the liver and brain, and also in peripheral tissues such as in the heart and gastrointestinal tract. Furthermore, adropin is present in the circulatory system. A decade after its discovery, there is evidence that adropin may contribute to body weight regulation, glucose and lipid homeostasis, and cardiovascular system functions. In this review, we summarize and discuss the physiological, metabolic, and pathophysiological factors regulating Enho as well as adropin. Furthermore, we review the literature addressing the role of adropin in adiposity and type 2 diabetes. Finally, we elaborate on the role of adropin in the context of the cardiovascular system, liver diseases, and cancer.

Seat belts-related behaviors in car drivers with cardiac implantable electronic devices.

BACKGROUND: Seat belt use is the single most effective means of reducing fatal injuries in road traffic accidents. The presence of a cardiac implantable electronic device (CIED) might influence seat belt-related behaviors due to the physical proximity of the seat belt and left subclavian area in which the device is usually implanted. Understanding the underlying mechanisms of improper seat belt use may improve safety of these patients. METHODS: We performed a prospective study using a structured questionnaire with 120 CIED recipients (age, 63.9 ± 10.9 years) attending a pacing outpatient clinic. All study participants were active drivers and predominantly male. The majority of patients (79%) had undergone high-energy device implantation. RESULTS: We found that 18% of study participants do not fasten seat belts on a regular basis or use the seat belt in an atypical fashion (such as under the armpit). Moderate or high level of discomfort from the interaction between seat belt and CIED was present in 27%, while more than half (51%) were afraid of seat belt-induced CIED damage. In multifactorial analysis, we found the following independent predictors of improper seat belt use: (1) at least moderate level of discomfort at the CIED site (P = 0.02); (2) fear of CIED damage (P = 0.009); and (3) irregular seat belt use prior to CIED implantation (P = 0.037). CONCLUSIONS: Improper seat belt-related behaviors are common in CIED recipients. They arise from previous habits and from CIED-related physical and psychological factors. Patients' education regarding the importance and safety of proper seat belt use is a priority.

Femoral avulsion fracture of ACL proximal attachment in male scuba diver: case report and review of the literature.

Femoral ACL avulsion fractures were not well described in the literature, and there were only several reports describing mostly immature patients. A case of 50-year-old man with ACL femoral attachment avulsion fracture after pivoting knee injury during skiing was presented. The bony attachment was reduced and fixed arthroscopically with screws. Four months after surgery, patient was allowed to return to full sport activity with full range of motion. He was able to perform a one-leg-hop test without limitation, and the strength of quadriceps muscle was comparable to contralateral side. Lachman and pivot shift tests were normal. Level of evidence IV.

Being overweight has limited effect on SCARF osteotomy outcome for hallux valgus correction.

PURPOSE: The purpose of this study was to investigate the association between body mass index (BMI) and the results of SCARF osteotomy of the first metatarsal for hallux valgus (HV) correction, as the literature on this is scant. METHODS: This prospective study was carried out between 2011 and 2015. One hundred and thirty-three patients diagnosed with moderate to severe HV underwent a SCARF corrective osteotomy. We divided the patients into two groups according to their BMI: normal and overweight. Postoperative follow-up was two years. All patients were examined twice by two medical doctors simultaneously: pre-operatively and post-operatively at two years' follow-up. Data collected included biometrical records, X-rays [HV angle (HVA), intermetatarsal angle (IMA), American Orthopaedic Foot and Ankle Society Hallux Metatarsophalangeal Index (AOFAS-HMI) and visual analogue scale (VAS) for pain and satisfaction]. RESULTS: There was a significant difference between patient age (p = 0.001), age at onset (p < 0.001) and AOFAS-HMI (p = 0.035) at follow-up. Other parameters were similar in both groups. CONCLUSION: Regardless of BMI, the radiological outcome was comparable. Despite a significant difference in AOFAS-HMI results, pain and satisfaction level were similar. The authors agreed that high BMI has protective role in the prevalence of HV.

Synthesis of arbitrary pulse waveforms in QCL-seeded ns-pulse CO2 laser for optimization of an LPP EUV source.

One of the unique features of the quantum-cascade-laser-seeded, nanosecond-pulse CO2 laser, invented for the purpose of generation of extreme UV by laser-produced-plasma, is a robust synthesis of arbitrary pulse waveforms. In the present Letter we report on experimental results that are, to our best knowledge, the first demonstration of such functionality obtainable from nanosecond-pulse CO2 laser technology. An online pulse duration adjustment within 10-40 ns was demonstrated, and a few exemplary pulse waveforms were synthesized, such as "tophat," "tailspike," and "leadspike" shapes. Such output characteristics may be useful to optimize the performance of LPP EUV source.