Atrophy is regarded a sensitive marker of neurodegenerative pathology. In addition to confirming the well-known presence of decreased global grey matter and hippocampal volumes in Alzheimer's ...disease, this study investigated whether deep grey matter structure also suffer degeneration in Alzheimer's disease, and whether such degeneration is associated with cognitive deterioration. In this cross-sectional correlation study, two groups were compared on volumes of seven subcortical regions: 70 memory complainers (MCs) and 69 subjects diagnosed with probable Alzheimer's disease. Using 3T 3D T1 MR images, volumes of nucleus accumbens, amygdala, caudate nucleus, hippocampus, pallidum, putamen and thalamus were automatically calculated by the FMRIB's Integrated Registration and Segmentation Tool (FIRST)—algorithm FMRIB's Software Library (FSL). Subsequently, the volumes of the different regions were correlated with cognitive test results. In addition to finding the expected association between hippocampal atrophy and cognitive decline in Alzheimer's disease, volumes of putamen and thalamus were significantly reduced in patients diagnosed with probable Alzheimer's disease. We also found that the decrease in volume correlated linearly with impaired global cognitive performance. These findings strongly suggest that, beside neo-cortical atrophy, deep grey matter structures in Alzheimer's disease suffer atrophy as well and that degenerative processes in the putamen and thalamus, like the hippocampus, may contribute to cognitive decline in Alzheimer's disease.
A new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently emerged to cause a human pandemic. Although molecular diagnostic tests were rapidly developed, serologic ...assays are still lacking, yet urgently needed. Validated serologic assays are needed for contact tracing, identifying the viral reservoir, and epidemiologic studies. We developed serologic assays for detection of SARS-CoV-2 neutralizing, spike protein-specific, and nucleocapsid-specific antibodies. Using serum samples from patients with PCR-confirmed SARS-CoV-2 infections, other coronaviruses, or other respiratory pathogenic infections, we validated and tested various antigens in different in-house and commercial ELISAs. We demonstrated that most PCR-confirmed SARS-CoV-2-infected persons seroconverted by 2 weeks after disease onset. We found that commercial S1 IgG or IgA ELISAs were of lower specificity, and sensitivity varied between the 2 assays; the IgA ELISA showed higher sensitivity. Overall, the validated assays described can be instrumental for detection of SARS-CoV-2-specific antibodies for diagnostic, seroepidemiologic, and vaccine evaluation studies.
Transition metal catalysis in confined spaces Leenders, Stefan H A M; Gramage-Doria, Rafael; de Bruin, Bas ...
Chemical Society reviews,
01/2015, Letnik:
44, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Transition metal catalysis plays an important role in both industry and in academia where selectivity, activity and stability are crucial parameters to control. Next to changing the structure of the ...ligand, introducing a confined space as a second coordination sphere around a metal catalyst has recently been shown to be a viable method to induce new selectivity and activity in transition metal catalysis. In this review we focus on supramolecular strategies to encapsulate transition metal complexes with the aim of controlling the selectivity via the second coordination sphere. As we will discuss, catalyst confinement can result in selective processes that are impossible or difficult to achieve by traditional methods. We will describe the template-ligand approach as well as the host-guest approach to arrive at such supramolecular systems and discuss how the performance of the catalyst is enhanced by confining it in a molecular container.
Purpose
Olaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for ovarian and metastatic breast cancer. Increased serum creatinine levels have been observed in patients taking ...olaparib, but the underlying mechanism is unknown. This study aimed to investigate if patients receiving olaparib have increased creatinine levels during olaparib treatment and whether this actually relates to a declined glomerular filtration rate (GFR).
Methods
We retrospectively identified patients using olaparib at the Netherlands Cancer Institute – Antoni van Leeuwenhoek (NKI-AVL) from 2012 until 2020. Patients with at least one plasma or serum sample available at baseline/off treatment and during olaparib treatment were included. Cystatin C levels were measured, creatinine levels were available and renal function was determined by calculating the estimated glomerular filtration rate (eGFR) using the Creatinine Equation (CKD-EPI 2009) and the Cystatin C Equation (CKD-EPI 2012).
Results
In total, 66 patients were included. Olaparib treatment was associated with a 14% increase in median creatinine from 72 (inter quartile range (IQR): 22) μmol/L before/off treatment to 82 (IQR: 20) μmol/L during treatment (
p
< 0.001) and a 13% decrease in median creatinine-derived eGFR from 86 (IQR: 26) mL/min/1.73 m
2
before/off treatment to 75 (IQR: 29) mL/min/1.73 m
2
during treatment (
p
< 0.001). Olaparib treatment had no significant effect on median cystatin C levels (
p
= 0.520) and the median cystatin C–derived eGFR (
p
= 0.918).
Conclusions
This study demonstrates that olaparib likely causes inhibition of renal transporters leading to a reversible and dose-dependent increase in creatinine and does not affect GFR, since the median cystatin C–derived eGFR was comparable before/off treatment and during treatment of olaparib. Using the creatinine-derived eGFR can give an underestimation of GFR in patients taking olaparib. Therefore, an alternative renal marker such as cystatin C should be used to accurately calculate eGFR in patients taking olaparib.
Summary
Background The Dermatology Department of the University Medical Centre Utrecht, the Netherlands, developed an e‐health portal for patients with atopic dermatitis (AD), consisting of ...e‐consultation, a patient‐tailored website, monitoring and self‐management training.
Objectives To determine the cost‐effectiveness of individualized e‐health compared with usual face‐to‐face care for children and adults with AD.
Methods A randomized controlled cost‐effectiveness study from a societal perspective in adults and parents of children with moderate AD. Outcomes were quality of life, severity of AD, itching and direct and indirect costs. Data were collected at baseline and at 3 and 12 months after randomization. Linear mixed models were used to analyse clinical outcomes. After multiple imputation of missing data, costs and differences in costs were calculated over a period of 1 year.
Results In total, 199 patients were included. There were no significant differences in disease‐specific quality of life, severity of AD and intensity of itching between both groups at the three time points. The difference in direct costs between the intervention and control groups was €24 95% confidence interval (CI) −360 to 383, whereas this difference was −€618 (95% CI −2502 to 1143) for indirect costs. Overall, individual e‐health was expected to save €594 (95% CI −2545 to 1227) per patient in the first year of treatment, mainly through a reduction in work absenteeism. Uncertainty analyses revealed that the probability of e‐health reducing costs was estimated to be ≥ 73%.
Conclusions E‐health during follow‐up of patients with AD is, after initial diagnosis and treatment during face‐to‐face contact, just as effective as usual face‐to‐face care with regard to quality of life and severity of disease. However, when costs are considered, e‐health is likely to result in substantial cost savings. Therefore, e‐health is a valuable service for patients with AD.
High rates of potentially pathogenic bacteria and respiratory viruses can be detected in the upper respiratory tract of healthy children. Investigating presence of and associations between these ...pathogens in healthy individuals is still a rather unexplored field of research, but may have implications for interpreting findings during disease.
We selected 986 nasopharyngeal samples from 433 6- to 24-month-old healthy children that had participated in a randomized controlled trial. We determined the presence of 20 common respiratory viruses using real-time PCR. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus were identified by conventional culture methods. Information on risk factors was obtained by questionnaires. We performed multivariate logistic regression analyses followed by partial correlation analysis to identify the overall pattern of associations. S. pneumoniae colonization was positively associated with the presence of H. influenzae (adjusted odds ratio 1.60, 95% confidence interval 1.18-2.16), M. catarrhalis (1.78, 1.29-2.47), human rhinoviruses (1.63, 1.19-2.22) and enteroviruses (1.97, 1.26-3.10), and negatively associated with S. aureus presence (0.59, 0.35-0.98). H. influenzae was positively associated with human rhinoviruses (1.63, 1.22-2.18) and respiratory syncytial viruses (2.78, 1.06-7.28). M. catarrhalis colonization was positively associated with coronaviruses (1.99, 1.01-3.93) and adenoviruses (3.69, 1.29-10.56), and negatively with S. aureus carriage (0.42, 0.25-0.69). We observed a strong positive association between S. aureus and influenza viruses (4.87, 1.59-14.89). In addition, human rhinoviruses and enteroviruses were positively correlated (2.40, 1.66-3.47), as were enteroviruses and human bocavirus, WU polyomavirus, parainfluenza viruses, and human parechovirus. A negative association was observed between human rhinoviruses and coronaviruses.
Our data revealed high viral and bacterial prevalence rates and distinct bacterial-bacterial, viral-bacterial and viral-viral associations in healthy children, hinting towards the complexity and potential dynamics of microbial communities in the upper respiratory tract. This warrants careful consideration when associating microbial presence with specific respiratory diseases.
Background
The complement system is an essential component of our innate defense and plays a vital role in the pathogenesis of many diseases. Assessment of complement activation is critical in ...monitoring both disease progression and response to therapy. Complement analysis requires accurate and standardized sampling and assay procedures, which has proven to be challenging.
Objective
We performed a systematic analysis of the current methods used to assess complement components and reviewed whether the identified studies performed their complement measurements according to the recommended practice regarding pre-analytical sample handling and assay technique. Results are supplemented with own data regarding the assessment of key complement biomarkers to illustrate the importance of accurate sampling and measuring of complement components.
Methods
A literature search using the Pubmed/MEDLINE database was performed focusing on studies measuring the key complement components C3, C5 and/or their split products and/or the soluble variant of the terminal C5b-9 complement complex (sTCC) in human blood samples that were published between February 2017 and February 2022. The identified studies were reviewed whether they had used the correct sample type and techniques for their analyses.
Results
A total of 92 out of 376 studies were selected for full-text analysis. Forty-five studies (49%) were identified as using the correct sample type and techniques for their complement analyses, while 25 studies (27%) did not use the correct sample type or technique. For 22 studies (24%), it was not specified which sample type was used.
Conclusion
A substantial part of the reviewed studies did not use the appropriate sample type for assessing complement activation or did not mention which sample type was used. This deviation from the standardized procedure can lead to misinterpretation of complement biomarker levels and hampers proper comparison of complement measurements between studies. Therefore, this study underlines the necessity of general guidelines for accurate and standardized complement analysis
Despite their significant influence on the quality of life, depressive symptoms are not usually included as a clinical parameter in the evaluation of hemodialysis patients. We aimed to identify ...depressive symptoms and associated risk factors in a large group of individuals with end-stage renal disease (ESRD) on chronic hemodialysis. This was a cross-sectional study of 400 consecutive patients. Cases were analyzed according to the presence/absence of depressive symptoms. All individuals were investigated by interview, and all variables were measured concurrently. Depressive symptoms were evaluated by the Beck Depression Inventory (BDI-II ≥16) and sleep quality by the Pittsburgh Sleep Quality Index (PSQI > 5). Among the 400 patients (59% male), depressive symptoms were present in 77 (19.3%). Depressive symptoms were more common in women and were independently associated with poor sleep quality (
P
= <0.005), unemployment (
P
= 0.001), diabetes (
P
= 0.02), hypoalbuminemia (
P
= 0.01), low education (
P
= 0.03), and pruritus (
P
= 0.04). Women with ESRD on chronic hemodialysis are at increased risk of depression. Furthermore, unemployment and the presence of diabetes, hypoalbuminemia, low education, and pruritus are significantly associated with depressive symptoms. Depressive symptoms are also independently associated with poor quality sleep and studies about the effects of sleep hygiene therapy on depressive symptoms are warranted.
Physical maneuvers can be applied to abort or delay an impending vasovagal faint. These countermaneuvers would be more beneficial if applied as a preventive measure. We hypothesized that, in patients ...with recurrent vasovagal syncope, leg crossing produces a rise in cardiac output (CO) and thereby in blood pressure (BP) with an additional rise in BP by muscle tensing. We analyzed the age and gender effect on the BP response. To confirm that, during the maneuvers, Modelflow CO changes in proportion to actual CO, 10 healthy subjects performed the study protocol with CO evaluated simultaneously by Modelflow and by inert gas rebreathing. Changes in Modelflow CO were similar in direction and magnitude to inert gas rebreathing-determined CO changes. Eighty-eight patients diagnosed with vasovagal syncope applied leg crossing after a 5-min free-standing period. Fifty-four of these patients also applied tensing of leg and abdominal muscles. Leg crossing produced a significant rise in CO (+9.5%; P < 0.01) and thereby in mean arterial pressure (+3.3%; P < 0.01). Muscle tensing produced an additional increase in CO (+8.3%; P < 0.01) and mean arterial pressure (+7.8%; P < 0.01). The rise in BP during leg crossing was larger in the elderly.
Does endometrial scratching in women with one failed IVF/ICSI treatment affect the chance of a live birth of the subsequent fresh IVF/ICSI cycle?
In this study, 4.6% more live births were observed in ...the scratch group, with a likely certainty range between -0.7% and +9.9%.
Since the first suggestion that endometrial scratching might improve embryo implantation during IVF/ICSI, many clinical trials have been conducted. However, due to limitations in sample size and study quality, it remains unclear whether endometrial scratching improves IVF/ICSI outcomes.
The SCRaTCH trial was a non-blinded randomised controlled trial in women with one unsuccessful IVF/ICSI cycle and assessed whether a single endometrial scratch using an endometrial biopsy catheter would lead to a higher live birth rate after the subsequent IVF/ICSI treatment compared to no scratch. The study took place in 8 academic and 24 general hospitals. Participants were randomised between January 2016 and July 2018 by a web-based randomisation programme. Secondary outcomes included cumulative 12-month ongoing pregnancy leading to live birth rate.
Women with one previous failed IVF/ICSI treatment and planning a second fresh IVF/ICSI treatment were eligible. In total, 933 participants out of 1065 eligibles were included (participation rate 88%).
After the fresh transfer, 4.6% more live births were observed in the scratch compared to control group (110/465 versus 88/461, respectively, risk ratio (RR) 1.24 95% CI 0.96-1.59). These data are consistent with a true difference of between -0.7% and +9.9% (95% CI), indicating that while the largest proportion of the 95% CI is positive, scratching could have no or even a small negative effect. Biochemical pregnancy loss and miscarriage rate did not differ between the two groups: in the scratch group 27/153 biochemical pregnancy losses and 14/126 miscarriages occurred, while this was 19/130 and 17/111 for the control group (RR 1.21 (95% CI 0.71-2.07) and RR 0.73 (95% CI 0.38-1.40), respectively). After 12 months of follow-up, 5.1% more live births were observed in the scratch group (202/467 versus 178/466), of which the true difference most likely lies between -1.2% and +11.4% (95% CI).
This study was not blinded. Knowledge of allocation may have been an incentive for participants allocated to the scratch group to continue treatment in situations where they may otherwise have cancelled or stopped. In addition, this study was powered to detect a difference in live birth rate of 9%.
The results of this study are an incentive for further assessment of the efficacy and clinical implications of endometrial scratching. If a true effect exists, it may be smaller than previously anticipated or may be limited to specific groups of women undergoing IVF/ICSI. Studying this will require larger sample sizes, which will be provided by the ongoing international individual participant data-analysis (PROSPERO CRD42017079120). At present, endometrial scratching should not be performed outside of clinical trials.
This study was funded by ZonMW, the Dutch organisation for funding healthcare research. J.S.E. Laven reports grants and personal fees from AnshLabs (Webster, Tx, USA), Ferring (Hoofddorp, The Netherlands) and Ministry of Health (CIBG, The Hague, The Netherlands) outside the submitted work. A.E.P. Cantineau reports 'other' from Ferring BV, personal fees from Up to date Hyperthecosis, 'other' from Theramex BV, outside the submitted work. E.R. Groenewoud reports grants from Titus Health Care during the conduct of the study. A.M. van Heusden reports personal fees from Merck Serono, personal fees from Ferring, personal fees from Goodlife, outside the submitted work. F.J.M. Broekmans reports personal fees as Member of the external advisory board for Ferring BV, The Netherlands, personal fees as Member of the external advisory board for Merck Serono, The Netherlands, personal fees as Member of the external advisory for Gedeon Richter, Belgium, personal fees from Educational activities for Ferring BV, The Netherlands, grants from Research support grant Merck Serono, grants from Research support grant Ferring, personal fees from Advisory and consultancy work Roche, outside the submitted work. C.B. Lambalk reports grants from Ferring, grants from Merck, grants from Guerbet, outside the submitted work.
Registered in the Netherlands Trial Register (NL5193/NTR 5342).
31 July 2015.
26 January 2016.
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