Objective The aim of the study was to explore the effect of a medical food intervention, developed to improve synaptic formation and function, on magnetoencephalography (MEG), as a proxy of ...macroscopic effects of synaptic changes, in patients with mild Alzheimer’s disease (AD). Methods In an exploratory 24-weeks, double blind, randomised controlled sub-study of the Souvenir II study, differences between the active ( n = 22) and control ( n = 27) drug-naïve mild AD patients were computed for frequency analysis, functional connectivity and functional brain network measures in source space MEG. Results The groups were significantly different with respect to baseline mini-mental state examination (MMSE) (active: 23.8 ± 2.3 (mean ± SD); control 25.3 ± 2.6). No consistent statistically significant intervention effects were found on the MEG measures. Conclusions In the current subsample of mild AD patients we could not detect an intervention effect of the medical food on MEG measures as opposed to EEG that has been used in a larger sample and revealed beneficial intervention effects on functional connectivity and brain network organisation in mild AD. Key message Further research is needed with substantially larger sample sizes and better balanced study groups to further assess the role of MEG in intervention trials in AD.
We used a visual analog scale (VAS) to assess the satisfaction after total knee arthroplasty (TKA) in a group of 108 patients (126 TKAs) with short-term to medium-term follow-up. We also used the ...Knee Society scoring system, Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC), pain VAS, and survival analysis. A comparison between the subjective and objective outcome systems revealed only poor correlations. This comparison suggests that the concerns and priorities of patients and surgeons differ. The outcome assessed with the satisfaction VAS revealed a significantly better subjective outcome in rheumatoid arthritis patients compared with osteoarthritis patients, whereas Knee Society scores were not different. The satisfaction VAS provides additional information about subjective outcome after TKA.
The role of GH insufficiency in the pathogenesis of short stature in Noonan syndrome is unclear.
Cross‐sectional study.
Seventeen patients with Noonan syn‐drome (13 boys, 4 girls; aged 4·8–13·3 (mean ...9·2) years) and short stature before start of GH treatment.
Spontaneous 12‐h overnight GH secretion by continuous sampling analysed using Pulsar, plasma IGF‐I and IGFBP‐3 levels, and 24‐h urinary GH excretion were measured at start of GH treatment. A glucagon stimulation test was performed. Height and height velocity were monitored before and after 1 year of GH treatment. IGF‐I and IGFBP‐3 were remeasured after 1 year of GH treatment.
Nine of the 17 children had a mean overnight GH concentration below the lower limit of the normal range. In six of the 17 patients, overnight GH profiles showed high trough GH concentrations. Glucagon stimulation tests were normal in 16 of the 17 patients. Mean IGF‐I level was below normal (−0·4 SD). None of the parameters regarding GH secretion obtained from the overnight profile or provocative test was related to height or height velocity, nor to first year response to GH treatment. IGF‐I and IGFBP‐3 did not correlate with any of the GH secretion data. IGF‐I and IGFBP‐3 were related to height and height velocity at the start of GH treatment (r = 0·53 (P < 0·01) and r = 0·61 (P < 0·03) respectively). Rises in IGF‐I and IGFBP‐3 under GH treatment were related to the increment in height velocity (r = 0·70 (P < 0·01) and r = 0·71 (P < 0·02) respectively).
Abnormalities in GH secretion are frequent in patients with Noonan syndrome and short stature. These abnormalities were not related to auxology at start of or response to GH treatment. Clinically GH insufficiency is not important in Noonan syndrome and monitoring spontaneous GH secretion is not necessary before the start of GH treatment.
In primary uveal and cutaneous melanoma lesions, extracellular matrix (ECM) is often deposited in arcs, loops, and network patterns. Based on prognostic relevance, these patterns appear to play a ...significant role in facilitating metastasis. It has been demonstrated that these patterns were capable of transmitting fluid. The current study was undertaken to elucidate further the functional role of these patterns in tumor perfusion and to examine the composition of the patterns by immunohistochemistry.
To study the role of these patterns in perfusion, fluorochrome-labeled bovine serum albumin, bovine insulin, and dextrans of different molecular sizes were injected intravenously into nude mice bearing subcutaneous human cutaneous melanoma xenografts. Distribution of the human melanoma cells and murine host cells was analyzed by DNA in situ hybridization. To elucidate the composition of these patterns, human uveal melanoma tissues were analyzed for expression of ECM components by immunohistochemistry.
Small molecules (Stokes' radius <4.4 nm) crossed the vessel wall and spread along the ECM patterns within 2 to 10 minutes, whereas larger molecules (Stokes' radius approximately 5.8 nm) required 30 to 45 minutes to enter. Murine host cells were found exclusively in the ECM pattern compartment. In primary uveal melanoma, different types of collagen, ECM-associated heparan sulfate proteoglycans, and different types of cells were present in the patterns.
The data suggest that the ECM deposited as arcs, loops, and network patterns, accommodate the transport of plasma-derived molecules, (e.g., nutrients), to the tumor lesion, thus enhancing tumor growth and progression, and facilitating infiltration of tumor tissue by host-derived cells.
The purpose of this study was to assess the accuracy of measuring angle and angular velocity of the upper body and upper leg during rising from a chair with accelerometers, using low-pass filtering ...of the accelerometer signal. Also, the improvement in accuracy of the measurement with additional use of high-pass filtered gyroscopes was assessed.
Two uni-axial accelerometers and one gyroscope (DynaPort) per segment were used to measure angles and angular velocities of upper body and upper leg. Calculated angles and angular velocities were compared to a high-quality optical motion analysis system (Optotrak), using root mean squared error (RMS) and correlation coefficient (
r
) as parameters.
The results for the sensors showed that two uni-axial accelerometers give a reasonable accurate measurement of the kinematics of rising from a chair (RMS=2.9, 3.5, and 2.6° for angle and RMS=9.4, 18.4, and 11.5°/s for angular velocity for thorax, pelvis, and upper leg, respectively). Additional use of gyroscopes improved the accuracy significantly (RMS=0.8, 1.1, and 1.7° for angle and RMS=2.6, 4.0 and 4.9°/s for angular velocity for thorax, pelvis and upper leg, respectively).
The low-pass Butterworth filter had optimal cut-off frequencies of 1.05, 1.3, and 1.05 for thorax, pelvis, and upper leg, respectively. For the combined signal, the optimal cut-off frequencies were 0.18, 0.2, and 0,38 for thorax, pelvis and upper leg, respectively. The filters showed no subject specificity.
This study provides an accurate, inexpensive and simple method to measure the kinematics of movements similar to rising from a chair.
Elephant and impala as intermediate feeders, having a mixed diet of grass and browse, respond to seasonal fluctuations of forage quality by changing their diet composition. We tested the hypotheses ...that (1) the decrease in forage quality is accompanied by a change in diet from more monocots in the wet season to more dicots in the dry season and that that change is more pronounced and faster in impala than in elephant; (2) mopane (Colophospermum mopane), the most abundant dicot species, is the most important species in the elephant diet in mopane woodland, whereas impala feed relatively less on mopane due to the high condensed tannin concentration; and (3) impala on nutrient-rich soils have a diet consisting of more grass and change later to diet of more browse than impala on nutrient-poor soils. The phosphorus content and in vitro digestibility of monocots decreased and the NDF content increased significantly towards the end of the wet season, whereas in dicots no significant trend could be detected. We argue that this decreasing monocot quality caused elephant and impala to consume more dicots in the dry season. Elephant changed their diet gradually over a 16-week period from 70% to 25% monocots, whereas impala changed diets rapidly (2–4 weeks) from 95% to 70% monocots. For both elephants and impala, there was a positive correlation between percentage of monocots and dicots in the diet and the in vitro digestibility of these forage items. Mopane was the most important dicot species in the elephant diet and its contribution to the diet increased significantly in the dry season, whereas impala selected other dicot species. On nutrient-rich gabbroic soils, impala ate significantly more monocots than impala from nutrient-poor granitic soils, which was related to the higher in vitro digestibility of the monocots on gabbroic soil. Digestibility of food items appears to be an important determinant of diet change from the wet to the dry season in impala and elephants.
Human interleukin-22 (IL-22), a cytokine with structural homology to IL-10, is produced by activated T cells. The IL-22 receptor complex consists of a ligand-binding chain, the IL-22R1 and a ...signal-transducing chain, the IL-10R2. The aim of this study is to identify potential target cells and associated biological activity of IL-22 by identifying cell types that specifically express high levels of IL-22R1 as the expression of IL-10R2 is ubiquitous. Expression of IL-22R1 mRNA, as analyzed by real time quantitative polymerase chain reaction (PCR), was observed in human tumor cell lines of stromal or epithelial origin derived from liver, pancreas, colon and lung tissue. Furthermore, we examined the ability of IL-22 to activate the JAK-Signal Transducer and Activator of Transcription (STAT) pathway in epithelial cells of the colon. IL-22 induced the phosphorylation of STAT1 and STAT3 in Colo205, a colon epithelial cell line. Consequently, IL-22 upregulated mRNA for Suppressor of Cytokine Signaling 3 (SOCS3), a STAT3-responsive gene. Further analyses, by real time quantitative PCR, on a panel of chemokines and immune function related genes revealed that IL-22 induced expression of the acute phase proteins α-Antichymotrypsin and Serum Amyloid A, as well as IL-10 mRNA and protein production by Colo205. Induction of IL-10 by IL-22, in Colo205 cells, could be inhibited in the presence of a neutralizing antibody against IL-10R2. IL-22-mediated effects on the Colo205 cells were also inhibited in the presence of IL-22 binding protein (IL-22BP), a soluble receptor with structural similarity to IL-22R1. The high levels of expression of IL-22R1 observed in epithelial cells of the colon and the ability of IL-22 to upregulate production of acute phase proteins and IL-10 in Colo205 cells, suggest a functional role for IL-22 in intestinal inflammation.
Data on the impact of human papillomavirus (HPV) vaccination on the population HPV prevalence are largely obtained from women. We assessed the impact of the girls‐only HPV16/18 vaccination program in ...the Netherlands that started in 2009, on trends in HPV prevalence among women and heterosexual men, using data from the PASSYON study. In this cross‐sectional study, the HPV prevalence among 16‐ to 24‐year‐old visitors to sexually transmitted infection clinics was assessed in 2009, 2011, 2013, and 2015. We compared the genital postvaccination HPV prevalence with the prevaccination prevalence (2009) using Poisson GEE models. In total, we included 4,996 women and 1,901 heterosexual men. The percentage of women who reported to be vaccinated increased from 2.3% in 2009 to 37% in 2015. Among all women, the HPV16/18 prevalence decreased from 23% prevaccination to 15% in 2015 (adjusted prevalence ratio aPR 0.62, ptrend < 0.01). Among heterosexual men, the HPV16/18 prevalence decreased from 17% prevaccination to 11% in 2015 (aPR 0.52, ptrend < 0.01). Of the heterosexual men with a steady partner, HPV16/18 prevalence was lower among those whose steady partner had been vaccine‐eligible in the national immunization program (aPR 0.13). Among unvaccinated women, the HPV16/18 prevalence in 2015 was not different from prevaccination. The decreasing HPV16/18 prevalence among heterosexual men and the reduced HPV16/18 prevalence among heterosexual men with a vaccine‐eligible steady partner strongly suggests herd protection from girls‐only vaccination. Absence of notable herd effects among unvaccinated women 6 years postvaccination may be due to the moderate vaccine uptake among girls in the Netherlands.
What's new?
Human papillomavirus (HPV) is a sexually transmitted virus that plays a causal role in the development of anogenital and oropharyngeal cancers in both men and women. The population‐level impact of HPV vaccination programs on the HPV prevalence has however mainly been studied in women. This study shows decreasing trends in the HPV16 and HPV18 prevalence among both women and heterosexual men after the introduction of a girls‐only HPV16/18 vaccination program in the Netherlands. The findings provide compelling evidence for herd protection in men. Because HPV16/18 are the most oncogenic types, HPV‐related cancers are expected to decline in both sexes after girls‐only HPV vaccination.
Primary uveal melanoma may contain arcs, loops, and networks of periodic acid-Schiff (PAS)-positive patterns, along which numerous macrophages are present. Their recruitment into tumor tissue is ...mediated by chemotactic cytokines, for which vascular endothelial growth factor (VEGF)-C and endothelial monocyte-activating polypeptide ((EMAP)-II are candidates. In this study, the extent of VEGF-C and EMAP-II immunoreaction was related to infiltration of macrophages.
Serial sections of 25 primary uveal melanoma lesions were analyzed by immunohistochemistry.
The analysis showed no correlation of VEGF-C immunoreaction and localization of macrophages. However, accumulation of macrophages occurred at sites of EMAP-II expression, especially in areas containing nests of tumor cells, surrounded by arcs, loops, and network patterns. In tumors with a strong EMAP-II immunoreaction, the adhesion molecule intracellular adhesion molecule (ICAM)-1 was strongly expressed on endothelial cells. EMAP-II-positive endothelial cells did not express VEGF receptor-2. However, extensive release of von Willebrand factor was observed. Signs of apoptosis were found neither in tumor cells nor endothelial cells.
In uveal melanoma, macrophages accumulate at sites of EMAP-II expression. Based on the results, it may be hypothesized that this process of chemotaxis is facilitated by EMAP-II-dependent expression of ICAM-1 on vascular endothelial cells and concomitantly leads to localized vascular damage, as indicated by release of von Willebrand factor.
Context:
Transient hypothyroxinemia of prematurity (THoP) has been associated with neurodevelopmental impairment in infancy and childhood. It is not known whether these relations persist into ...adulthood.
Objective:
The objective was to examine whether there is an effect of THoP on intelligence quotient (IQ) score and motor functioning at a young adult age.
Design:
This study was part of the 19-year follow-up of the Project On Preterm and Small-for-gestational-age birth (POPS) cohort, which included infants born very preterm (ie, <32 wk) and/or with a very low birth weight (ie, <1500 g).
Setting:
This was a multicenter study.
Patients:
There were 398 19-year-old participants of the POPS cohort, of whom 120 had THoP.
Exposure:
T4 concentrations were obtained through the national neonatal screening program for congenital hypothyroidism. THoP was defined as a total T4 concentration < −3 SD of the daily mean (approximately 60 nmol/L).
Main Outcome Measures:
Main outcome measures were IQ and motor functioning, measured with the digital Multicultural Capacities Test-Intermediate Level and a revised version of Touwen's examination of minor neurological dysfunction, respectively.
Results:
THoP was not associated with IQ score (mean difference, 0 95% confidence interval, −3.8 to 3.8 points) or motor function (mean difference, 0.6 95% confidence interval, −1.3 to 2.5 points) after adjustment for demographic and perinatal characteristics.
Conclusions:
No associations between THoP and neurodevelopmental outcome at age 19 years were found.
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