Purpose Visual height intolerance (vHI) occurs when a trigger causes the apprehension of losing balance and falling. Depending on the severity of vHI, an avoidance behavior may develop in about 50 % ...of the thus afflicted, and it can have considerable impact on their daily life and interpersonal interactions. It seems obvious that such experiences may be impairing and distressing, but this has not yet been examined systematically. Objective of this study was to examine the consequences of vHI for quality of life. Methods A qualitative, phenomenological exploratory approach was chosen. Individual face-to-face interviews were conducted with individuals who had reported in a previous study that they were susceptible to vHI. The interview transcripts were segregated into distinct meaning units, which were used to create a coding guideline with meta- and subcodes. Meaning units were then systematically extracted and assigned to the appropriate codes. Weights and links were used to assign priorities for interpretation. Results Eighteen participants were interviewed (mean age 53, range 30–73; 11 females). Data analysis resulted in 29 meta-codes and 115 subcodes. Responses indicated that vHI can be very disabling and has a relevant impact on quality of life and daily activities of the affected persons, including their family life and behavior towards partner, children and friends. Conclusion Relevant topics for further quantitative studies were identified, for example, strategies of compensation and the influence of vHI on family life. Other quantitative studies should determine whether comorbidities and the typologies found in this study have consequences for individual therapeutic approaches.
Background
C1q/TNF‐related protein‐3 (CTRP‐3) represents a novel anti‐inflammatory and antidiabetic adipokine secreted by adipose tissue. The physiological and postprandial regulation of CTRP‐3 ...remains obscure and it is not known whether CTRP‐3 is permeable to the brain. The postprandial regulation of CTRP‐3 during an oral glucose tolerance test (n = 100) and an oral lipid tolerance test (n = 100) in humans was investigated. Moreover, CTRP‐3 concentrations were measured in paired serum and cerebrospinal fluid (CSF) samples of patients (n = 270) undergoing neurological evaluation. The expression of CTRP‐3 mRNA was investigated in adipocytes upon stimulation with glucose, sex hormones and a broad panel of fatty acids.
Materials and methods
Serum and CSF CTRP‐3 concentrations were measured by ELISA. 3T3‐L1 adipocytes were used for stimulation experiments. CTRP‐3 mRNA expression was quantified by using real‐time PCR analysis.
Results
CTRP‐3 is present in human cerebrospinal fluid with a mean CSF/serum ratio of 110 ± 64 × 10−3. CTRP‐3 is not regulated postprandially by carbohydrates or lipids in the healthy state. Females have slightly higher levels of CTRP‐3 when compared to males. A significant and positive correlation of CTRP‐3 to LDL cholesterol serum levels is reproducible in several cohorts and deserves further mechanistic investigation. Whereas glucose concentrations do not influence CTRP‐3 mRNA expression in 3T3‐L1 adipocytes in vitro, fatty acids differentially modulate CTRP‐3 expression.
Conclusions
The novel adipokine CTRP‐3 is detectable in human cerebrospinal fluid (proof of principle). Due to its blood–brain barrier permeability, CTRP‐3 represents a novel putative candidate for a physiological regulator molecule affecting central nervous functions.
Six pheochromocytoma susceptibility genes causing distinct syndromes have been identified; approximately one of three of all pheochromocytoma patients carry a predisposing germline mutation. When ...four major genes (VHL, RET, SDHB, SDHD) are analyzed in a clinical laboratory, costs are approximately $3,400 per patient. The aim of the study is to systematically obtain a robust algorithm to identify who should be genetically tested, and to determine the order in which genes should be tested.
DNA from 989 apparently nonsyndromic patients were scanned for germline mutations in the genes VHL, RET, SDHB, SDHC, and SDHD. Clinical parameters were analyzed as potential predictors for finding mutations by multiple logistic regression, validated by bootstrapping. Cost reduction was calculated between prioritized gene testing compared with that for all genes.
Of 989 apparently nonsyndromic pheochromocytoma cases, 187 (19%) harbored germline mutations. Predictors for presence of mutation are age <45 years, multiple pheochromocytoma, extra-adrenal location, and previous head and neck paraganglioma. If we used the presence of any one predictor as indicative of proceeding with gene testing, then 342 (34.6%) patients would be excluded, and only 8 carriers (4.3%) would be missed. We were also able to statistically model the priority of genes to be tested given certain clinical features. E.g., for patients with prior head and neck paraganglioma, the priority would be SDHD>SDHB>RET>VHL. Using the clinical predictor algorithm to prioritize gene testing and order, a 44.7% cost reduction in diagnostic process can be achieved.
Clinical parameters can predict for mutation carriers and help prioritize gene testing to reduce costs in nonsyndromic pheochromocytoma presentations.
The adiponectin paralog CORS-26 (collagenous repeat-containing sequence of 26
kDa protein) is a member of the C1q/TNF-α molecular superfamily. CORS-26 is a secreted protein and baculovirus-produced ...CORS-26 released in the supernatant of insect cells forms stable trimers. Adiponectin exerts anti-inflammatory effects in LPS-treated monocytic cells and CORS-26 also reduces IL-6 and TNF-α secretion but does not increase IL-10. Suppression of NFκB signalling may explain the anti-inflammatory actions of CORS-26. Furthermore CORS-26 protein was detected in human monocytic and dendritic cells. The present data demonstrate for the first time that CORS-26 forms trimers, exerts anti-inflammatory properties and that it is expressed in monocytic cells. Therefore CORS-26 may provide a new target for pharmacological drugs in inflammatory diseases like the metabolic syndrome.
Summary
Context
Data on quantification and regulation of adipsin in human cerebrospinal fluid (CSF) are sparse, and the physiological role of adipsin as an adipokine crossing the blood–brain barrier ...(BBB) is uncertain.
Objectives
This study quantified adipsin concentrations in paired serum and CSF samples of patients undergoing neurological evaluation and spinal puncture.
Design
A total of 270 consecutive patients with specified neurological diagnosis were included in this study without prior selection.
Main outcome measures
Adipsin serum and CSF concentrations were measured by ELISA. A variety of serum and CSF routine parameters were measured by standard procedures. Anthropometric data, medication and patient history were available.
Results
Adipsin concentrations ranged between 467 and 5148 ng/ml in serum and between 4·2 and 133·5 ng/ml in CSF. Serum adipsin concentrations were correlated positively with respective CSF concentrations and were approximately 40‐fold higher when compared to CSF. The mean CSF/serum ratio for adipsin was 27 ± 22 × 10−3. Serum and CSF adipsin levels were independent of gender and significantly higher in overweight/obese individuals. Serum and CSF adipsin levels correlated significantly with age and were higher in patients suffering from diabetes mellitus or hypertension. CSF adipsin concentrations showed a significant correlation with markers of inflammation in CSF, but not with CSF total cell count or the presence of oligoclonal bands. Patients suffering from infectious diseases had higher CSF levels of adipsin than multiple sclerosis patients.
Conclusions
Adipsin is present in human CSF under pathophysiological conditions. The positive correlation between serum and CSF concentrations, the positive correlation between the CSF/serum ratios for adipsin and total protein and the lack of association with CSF cell count argue against an autochthonous production in the central nervous system. In contrast, the present data argue for a significant BBB permeability to adipsin.
Background:
Visfatin represents an adipokine of the visceral adipose tissue exerting pleiotropic effects. The aim of the study was to characterize the physiological regulation of visfatin release in ...vivo in healthy, nondiabetic probands and in adipocytes in vitro.
Subjects and Methods:
One hundred healthy subjects (64 females and 36 males) underwent an oral glucose tolerance test (75 g). Probands were characterized by anthropometric and laboratory parameters. Fasting and postprandial (1 and 2 h) serum concentrations of glucose, insulin, and visfatin were measured. Stimulation experiments using glucose, insulin, mannitol, and glucagon-like peptide-1 (GLP-1) were performed on 3T3-L1 adipocytes including Western blot analysis.
Results:
Fasting visfatin levels were not different between males/females or lean/obese individuals but were negatively (r = −0.5; P < 0.001) correlated with fasting glucose levels. Visfatin levels were rapidly and significantly suppressed (P < 0.001) upon an oral glucose intake, and this suppression was more pronounced in overweight and female probands. In vitro experiments demonstrated that hyperglycemia, osmotic stress, and sex steroids did not influence visfatin release. In contrast, insulin strongly (P = 0.002) inhibited visfatin release in vitro by approximately 50%, and this suppression was more pronounced under hyperglycemia. Importantly, GLP-1 strongly (P < 0.001) inhibited adipocytic visfatin release by approximately 50%.
Conclusions:
Insulin and GLP-1 are responsible for the rapid suppression of visfatin levels upon an oral glucose uptake in healthy probands. The inhibitory effect of GLP-1 on adipocytic visfatin release together with the absence of direct glucose effects on visfatin release suggests the existence of a novel incretin-like effect represented by a GLP-1/visfatin/axis.
Acromegaly is a rare disease with significant morbidity and increased mortality. Epidemiological data about therapeutic outcome under 'real life' conditions are scarce.
To describe biochemical ...long-term outcome of acromegaly patients in Germany.
Retrospective data analysis from 1344 patients followed in 42 centers of the German Acromegaly Register. Patients' data were collected 8.6 (range 0-52.6) years after diagnosis. Controlled disease was defined by an IGF1 within the center-specific reference range.
Nine hundred and seventeen patients showed a normalized IGF1 (157 (range 25-443) ng/ml). In patients with a diagnosis dated back >2 years (n=1013), IGF1 was normalized in 76.9%. Of the patients, 19.5% had an elevated IGF1 and a random GH ≥1 ng/ml, 89% of the patients had at least one surgical intervention, 22% underwent radiotherapy, and 43% received medical treatment. After surgery 38.8% of the patients were controlled without any further therapy. The control rates were higher in surgical centers with a higher caseload (P=0.034). Of the patients with adjunctive radiotherapy 34.8% had a normal IGF1 8.86 (0-44.9) years post irradiation, 65.2% of the medically treated patients were controlled, and 47.2% of the patients with an elevated IGF1 received no medical therapy.
The majority of acromegaly patients were controlled according to their IGF1 status. Long-term outcome could be improved by exploiting medical treatment options especially in patients who are not controlled by surgery and/or radiotherapy.
► Conjugated bile acids increase after glucose intake. ► Unconjugated bile acids decrease after glucose intake. ► Bile acid synthesis is repressed. ► FGF19 is elevated 2
h after glucose intake.
...Monitoring bile acids as signal molecules in combination with a bile acid synthesis marker and the FXR regulator fibroblast growth factor 19 (FGF19), this study addresses significant postprandial changes. The efficacy of the different pathways to regulate bile acid synthesis through short heterodimer partner (SHP) dependent FXR modulation in liver, and SHP independent activation via FGF19 is demonstrated. Characteristic changes of the bile acid profile during an oral glucose tolerance test (oGTT) were investigated in 73 individuals. 15 bile acid species including conjugated and unconjugated forms were quantitatively determined with LC–MS/MS in serum samples collected at three time points during the oGTT. All conjugated bile acid species showed the same time course, a significant increase at 60
min after the glucose intake and an incline at 120
min. In contrast, a consistent decline of all unconjugated bile acids was monitored. 7α-Hydroxy-4-cholesten-3-one, an early bile acid synthesis marker, showed an inverse response with a significant decrease at 60
min which proves the efficient and rapid downregulation of CYP7A1 via FXR activation through bile acid signaling. Significantly higher levels of FGF19 were observed 120
min after glucose intake and 60
min after bile acid excursion.
A convenient, aqueous-based synthesis of stable HgTe nanocrystals with widely size-tunable room temperature emission between wavelengths of 1.2 to 3.7 μm is demonstrated. By the choice of the thiols, ...applied as stabilizers, we optimized the growth dynamics, the luminescence quantum yields (up to 40%), and a ligand-exchange procedure, required to transfer the nanocrystals from water to nonpolar organic solvents. The latter is greatly improved and facilitated by the use of mercaptoethylamine as initial stabilizer. The possibility to tune the HgTe nanocrystal sizes from 3 to 12 nm and to control their surface functionalities (hydrophobic and hydrophilic) makes them very promising for the development of infrared optical devices, emitting in the wavelength region between the telecommunications and the molecular vibrations.
Studies have shown that pregnant women with COVID-19 have a higher risk of intensive care unit admission and invasive mechanical ventilation support than non-pregnant women. Pregnancy-associated ...physiological changes in respiratory function may contribute to the elevated risk. Alteration in lung volumes and capacities are attributed to the mechanical impediment caused by the growing fetus. Multiple pregnancies may therefore compromise functional lung capacity earlier than singleton pregnancies and contribute to severe respiratory symptoms of COVID-19.
A total of 5514 women with a symptomatic SARS-CoV-2 infection during pregnancy registered in the COVID-19 Related Obstetric and Neonatal Outcome Study were included. The COVID-19-related adverse maternal outcomes were compared in 165 multiple versus 5349 singleton pregnancies. Combined adverse maternal outcome was defined as presence of COVID-19-related hospitalization and/or pneumonia and/or oxygen administration and/or transfer to ICU and/or death. Multivariate logistic regression was used to estimate the odds ratios and 95% confidence intervals were calculated.
The frequency of dyspnea, likelihood of developing dyspnea in a defined pregnancy week and duration of the symptomatic phase of the COVID-19 infection did not differ between the two groups. On average, COVID-19-related combined adverse outcome occurred earlier during pregnancy in women expecting more than one child than in singleton pregnancies. The overall incidence of singular and combined COVID-19-associated adverse maternal outcomes was not significantly different between groups. However, regression analysis revealed that multiple gestation, preconceptional BMI > 30 kg/m
and gestational age correlated significantly with an increased risk of combined adverse maternal outcome. Conversely, maternal age and medically assisted reproduction were not significant risk factors for combined adverse maternal outcome.
Our data show that multiple gestation alone is a risk factor for COVID-19-associated combined adverse maternal outcome. Moreover, severe courses of COVID-19 in women expecting more than one child are observed earlier in pregnancy than in singleton pregnancies.
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