Our aim was to design a study to evaluate the effectiveness and cost-effectiveness of adding physiotherapy to conventional treatment for children with functional constipation in primary care. ...Physiotherapy is focusing on improving the coordination between the pelvic floor and abdominal musculature during bowel movement, while conventional treatment is mainly focusing on symptomatic relief of symptoms, therefore, we expect the effects of physiotherapy will be more sustainable than the effects of conventional treatment. In this paper we describe the final study design and how the design was adapted, to overcome recruitment problems.
We designed a randomized controlled trial of children aged 4-17 years with functional constipation diagnosed by a general practitioner or pediatrician. Children in the intervention group received physiotherapy plus conventional treatment, and those in the control group received conventional treatment only. Follow-up measurements took place at 4 and 8 months. The primary outcome was treatment success defined according to the Rome-III criteria as the absence of functional constipation, with no laxative use. Secondary outcomes were absence of functional constipation irrespective of laxative use, quality of life, global perceived effect, and costs. Children were recruited from September 2014 to February 2017. Initially, we aimed to include children with recent symptom onset. However, in the first phase of enrollment we were confronted with an unforeseen recruitment problem: many children and their parents refused randomization because physiotherapy was considered too burdensome for the stage of disease. Therefore, we decided to also include children with a longer duration of symptoms. In total 134 children were included.
The target number of participants is achieved. Therefore, the results may change thinking about the management of functional constipation in children.
Netherlands Trial Register ( NTR4797 ), registered 8 September 2014.
In the present study 11 perfluoroalkylated substances (PFASs) were analysed in drinking tap water samples from the Netherlands (n = 37) and from Greece (n = 43) by applying LC-MS/MS and isotope ...dilution. PFASs concentrations above the limit of quantification, LOQ (0.6 ng/l) were detected in 20.9% of the samples from Greece. Total PFAS concentrations ranged between 8) were only rarely detected. In the drinking water samples from the eastern part of the Netherlands, where drinking water is sourced from groundwater reservoirs, no PFASs were detected. This demonstrates that exposure to PFASs through drinking water in the Netherlands is dependent on the source. Additionally, five samples of bottled water from each country were analysed in the current study, with all of them originating from ground wells. In these samples, all PFASs were below the LOQ.
Beyond social learning Singh, Manvir; Acerbi, Alberto; Caldwell, Christine A. ...
Philosophical transactions - Royal Society. Biological sciences,
07/2021, Letnik:
376, Številka:
1828
Journal Article
Recenzirano
Odprti dostop
Cultural evolution requires the social transmission of information. For this reason, scholars have emphasized social learning when explaining how and why culture evolves. Yet cultural evolution ...results from many mechanisms operating in concert. Here, we argue that the emphasis on social learning has distracted scholars from appreciating both the full range of mechanisms contributing to cultural evolution and how interactions among those mechanisms and other factors affect the output of cultural evolution. We examine understudied mechanisms and other factors and call for a more inclusive programme of investigation that probes multiple levels of the organization, spanning the neural, cognitive-behavioural and populational levels. To guide our discussion, we focus on factors involved in three core topics of cultural evolution: the emergence of culture, the emergence of cumulative cultural evolution and the design of cultural traits. Studying mechanisms across levels can add explanatory power while revealing gaps and misconceptions in our knowledge.
This article is part of the theme issue ‘Foundations of cultural evolution’.
Elastosis in ERα-positive male breast cancer Vermeulen, Marijn A.; van Deurzen, Carolien H. M.; van Leeuwen-Stok, A. Elise ...
Virchows Archiv,
02/2021, Letnik:
478, Številka:
2
Journal Article
Recenzirano
Odprti dostop
In female breast cancer (BC), elastosis is strongly related to estrogen receptor alpha (ERα) expression. Male breast cancers almost invariably express ERα; so, the aim of this study was to ...investigate elastosis frequency in invasive male BC as well as clinicopathological correlations, in comparison with females. A total of 177 male BC cases and 135 female BC cases were included, all ERα-positive and invasive carcinoma of no special type. Elastosis on H&E-stained slides was scored in a four-tiered system as elastosis grade (EG) 0 (no elastosis) to EG3 (high amount of elastosis). EG scores in male BC were correlated to histopathological characteristics and overall surviva and compared with female BC EG scores. Male BC showed some degree of elastosis in 26/117 cases (22.2%) with none showing EG3, while female BC cases showed elastosis in 89/135 cases (65.9%) with 21.5% showing EG3 (
p
< 0.001). This difference retained its significance in multivariate logistic regression. In male BC cases, no significant correlations were found between the amount of elastosis and age, grade, mitotic activity index, and PgR. In addition, no significant prognostic value of elastosis was seen. In conclusion, despite high ERα expression, male BC showed significantly less elastosis than female BC. Elastosis did not show clinicopathological correlations or prognostic value. Therefore, elastosis seems to be a less useful ERα tissue biomarker with less clinical significance in male BC compared with females, pointing towards important BC sex differences.
Klotho Prevents Renal Calcium Loss ALEXANDER, R. Todd; WOUDENBERG-VRENKEN, Titia E; BUURMAN, Jan ...
Journal of the American Society of Nephrology,
11/2009, Letnik:
20, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Disturbed calcium (Ca(2+)) homeostasis, which is implicit to the aging phenotype of klotho-deficient mice, has been attributed to altered vitamin D metabolism, but alternative possibilities exist. We ...hypothesized that failed tubular Ca(2+) absorption is primary, which causes increased urinary Ca(2+) excretion, leading to elevated 1,25-dihydroxyvitamin D(3) 1,25(OH)(2)D(3) and its sequelae. Here, we assessed intestinal Ca(2+) absorption, bone densitometry, renal Ca(2+) excretion, and renal morphology via energy-dispersive x-ray microanalysis in wild-type and klotho(-/-) mice. We observed elevated serum Ca(2+) and fractional excretion of Ca(2+) (FE(Ca)) in klotho(-/-) mice. Klotho(-/-) mice also showed intestinal Ca(2+) hyperabsorption, osteopenia, and renal precipitation of calcium-phosphate. Duodenal mRNA levels of transient receptor potential vanilloid 6 (TRPV6) and calbindin-D(9K) increased. In the kidney, klotho(-/-) mice exhibited increased expression of TRPV5 and decreased expression of the sodium/calcium exchanger (NCX1) and calbindin-D(28K), implying a failure to absorb Ca(2+) through the distal convoluted tubule/connecting tubule (DCT/CNT) via TRPV5. Gene and protein expression of the vitamin D receptor (VDR), 25-hydroxyvitamin D-1-alpha-hydroxylase (1alphaOHase), and calbindin-D(9K) excluded renal vitamin D resistance. By modulating the diet, we showed that the renal Ca(2+) wasting was not secondary to hypercalcemia and/or hypervitaminosis D. In summary, these findings illustrate a primary defect in tubular Ca(2+) handling that contributes to the precipitation of calcium-phosphate in DCT/CNT. This highlights the importance of klotho to the prevention of renal Ca(2+) loss, secondary hypervitaminosis D, osteopenia, and nephrocalcinosis.
The Late Effects of Childhood Cancer task force of the Dutch Childhood Oncology Group (DCOG LATER) developed a guideline for follow-up of asymptomatic cardiac dysfunction in childhood cancer ...survivors (CCS). In this paper, we present the methods, available evidence and final recommendations of our guideline.
A multidisciplinary working group specified clinical questions that should be answered to get to recommendations for the guideline. We carried out short or extensive evidence summaries and determined methodological quality of studies and levels of evidence in order to answer all clinical questions. When evidence was lacking for CCS, we carefully extrapolated evidence from other populations. Final recommendations were based on evidence and consensus.
There was high-level evidence for the increased risk of cardiac dysfunction in CCS and its main risk factors. Evidence was lacking regarding the prognosis, diagnosis and treatment of cardiac dysfunction in CCS. We recommended echocardiographic screening for asymptomatic cardiac dysfunction in CCS treated with cardiotoxic treatments and counseling about potential advantages and disadvantages of our screening recommendations.
The DCOG LATER guideline recommends risk-based screening for asymptomatic cardiac dysfunction in CCS, but it should be noted that recommendations are not completely supported by evidence in CCS.
This study aimed to evaluate the histopathological concordance rates between prostate biopsies and radical prostatectomy specimens according to the applied biopsy approach (transrectal or ...transperineal).
We studied patients who had been newly diagnosed with clinically significant prostate cancer and who underwent a radical prostatectomy between 2018 and 2022. Patients were included if they underwent a prebiopsy magnetic resonance imaging and if they had not been previously treated for prostate cancer. Histopathological grading on prostate biopsies was compared with that on radical prostatectomy specimens. Univariable and multivariable logistic regression analyses were performed to assess the effect of the applied biopsy approach on histopathological concordance. Additional analyses were performed to assess the effect of the applied biopsy approach on American Urological Association risk group migration, defined as any change in risk group after radical prostatectomy.
In total, 1058 men were studied, of whom 49.3% (522/1058) and 50.7% (536/1058) underwent transrectal and transperineal prostate biopsies, respectively. Histopathological disconcordance was observed in 37.8% (400/1058) of men while American Urological Association risk group migration was observed in 30.2% (320/1058) of men. A transperineal biopsy approach was found to be independently associated with higher histopathological concordance rates (OR 1.33 95% CI 1.01-1.75, p = 0.04) and less American Urological Association risk group migration (OR 0.70 95% CI 0.52-0.93, p = 0.01).
The use of a transperineal biopsy approach improved histopathological concordance rates compared to the use of a transrectal biopsy approach. A transperineal biopsy approach may provide more accurate risk stratification for clinical decision-making. Despite recent improvements, histopathologic concordance remains suboptimal and should be considered before initiating management.
The introduction of rituximab significantly improved the prognosis of diffuse large B-cell lymphoma (DLBCL), emphasizing the importance of evaluating the long-term consequences of exposure to ...radiotherapy, alkylating agents and anthracycline-containing (immuno)chemotherapy among DLBCL survivors.
Long-term risk of subsequent malignant neoplasms (SMNs) was examined in a multicenter cohort comprising 2373 5-year DLBCL survivors treated at ages 15-61 years in 1989-2012. Observed SMN numbers were compared with expected cancer incidence to estimate standardized incidence ratios (SIRs) and absolute excess risks (AERs/10 000 person-years). Treatment-specific risks were assessed using multivariable Cox regression.
After a median follow-up of 13.8 years, 321 survivors developed one or more SMNs (SIR 1.5, 95% CI 1.3-1.8, AER 51.8). SIRs remained increased for at least 20 years after first-line treatment (SIR ≥20-year follow-up 1.5, 95% CI 1.0-2.2, AER 81.8) and were highest among patients ≤40 years at first DLBCL treatment (SIR 2.7, 95% CI 2.0-3.5). Lung (SIR 2.0, 95% CI 1.5-2.7, AER 13.4) and gastrointestinal cancers (SIR 1.5, 95% CI 1.2-2.0, AER 11.8) accounted for the largest excess risks. Treatment with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin versus ≤2250 mg/m2/≤150 mg/m2, respectively, was associated with increased solid SMN risk (hazard ratio 1.5, 95% CI 1.0-2.2). Survivors who received rituximab had a lower risk of subdiaphragmatic solid SMNs (hazard ratio 0.5, 95% CI 0.3-1.0) compared with survivors who did not receive rituximab.
Five-year DLBCL survivors have an increased risk of SMNs. Risks were higher for survivors ≤40 years at first treatment and survivors treated with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin, and may be lower for survivors treated in the rituximab era, emphasizing the need for studies with longer follow-up for rituximab-treated patients.
•Five-year DLBCL survivors have a higher risk of subsequent solid and hematological malignancies than the general population.•Largest excess risks were observed for subsequent lung and gastrointestinal tract cancer.•Receipt of >4500 mg/m2 cyclophosphamide (versus ≤2250 mg/m2) is associated with a 1.5-fold increased solid malignancy risk.•Risk may be lower for survivors treated in the rituximab era, emphasizing the need for studies with longer follow-up.
Accurate identification of cacti, whether seen as an indicator of ecosystem health or an invasive menace, is important. Technological improvements in hyperspectral remote sensing systems with high ...spatial resolutions make it possible to now monitor cacti around the world. Cacti produce a unique spectral signature because of their morphological and anatomical characteristics. We demonstrate in this paper that we can leverage a reflectance dip around 972 nm, due to cacti’s morphological structure, to distinguish cacti vegetation from non-cacti vegetation in a desert landscape. We also show the ability to calculate two normalized vegetation indices that highlight cacti. Furthermore, we explore the impacts of spatial resolution by presenting spectral signatures from cacti samples taken with a handheld field spectroradiometer, drone-based hyperspectral sensor, and aerial hyperspectral sensor. These cacti indices will help measure baseline levels of cacti around the world and examine changes due to climate, disturbance, and management influences.
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