Quality of life in menopausal women in the workplace - a systematic review.

Menopausal women are a large and economically relevant group in the workforce. Yet their quality of life (QoL) and needs in the workplace have been neglected. Thus, the aim of this systematic review was to provide an overview of QoL of menopausal women in the workplace. Systematic literature searches were executed, yielding 1211 references. After abstract screening, 156 articles remained for full-text screening. Finally, 12 articles fulfilled the inclusion criteria and were included in this review. Age, educational level, type of work, working environment (e.g. crowding, confined spaces, noise, workstation design), permanent place of residency, mental factors (e.g. stress level, workload, work pattern), comorbidities, menopausal symptoms, time since menopause and physical activity have repeatedly been shown to affect QoL in the workplace in menopausal women. Low-threshold access to medical and psychological support as well as individual adaptation of the workplace environment are, among others, retrieved recommendations for employers from these findings. Further raising of awareness of special needs of menopausal working women as well as further systematic research programs are needed.

Pro-fibrotic phenotype of bone marrow stromal cells in Modic type 1 changes.

Modic type 1 changes (MC1) are painful vertebral bone marrow lesions frequently found in patients suffering from chronic low-back pain. Marrow fibrosis is a hallmark of MC1. Bone marrow stromal cells (BMSCs) are key players in other fibrotic bone marrow pathologies, yet their role in MC1 is unknown. The present study aimed to characterise MC1 BMSCs and hypothesised a pro-fibrotic role of BMSCs in MC1. BMSCs were isolated from patients undergoing lumbar spinal fusion from MC1 and adjacent control vertebrae. Frequency of colony-forming unit fibroblast (CFU-F), expression of stem cell surface markers, differentiation capacity, transcriptome, matrix adhesion, cell contractility as well as expression of pro-collagen type I alpha 1, α-smooth muscle actin, integrins and focal adhesion kinase (FAK) were compared. More CFU-F and increased expression of C-X-C-motif-chemokine 12 were found in MC1 BMSCs, possibly indicating overrepresentation of a perisinusoidal BMSC population. RNA sequencing analysis showed enrichment in extracellular matrix proteins and fibrosis-related signalling genes. Increases in pro-collagen type I alpha 1 expression, cell adhesion, cell contractility and phosphorylation of FAK provided further evidence for their pro-fibrotic phenotype. Moreover, a leptin receptor high expressing (LEPRhigh) BMSC population was identified that differentiated under transforming growth factor beta 1 stimulation into myofibroblasts in MC1 but not in control BMSCs. In conclusion, pro-fibrotic changes in MC1 BMSCs and a LEPRhigh MC1 BMSC subpopulation susceptible to myofibroblast differentiation were found. Fibrosis is a hallmark of MC1 and a potential therapeutic target. A causal link between the pro-fibrotic phenotype and clinical characteristics needs to be demonstrated.

Late onset pulmonary embolism in young male otherwise healthy COVID-19 patients.

SARS-CoV-2 infection is associated with increased risk of thrombosis in severely ill patients but little is known about the risk in outpatients with mild to moderate disease. Our case series consists of four male otherwise healthy patients between 32 and 50 years of age. Initial symptoms completely resolved but they developed new onset of dyspnea and thoracic pain at days 14 to 26. CT scan revealed pulmonary embolism in all patients which led to hospitalization. Standard anticoagulation practice needs to be re-evaluated and may  be considered for certain outpatients with COVID-19.

Effects of an 8-week aerobic exercise program on plasma markers for cholesterol absorption and synthesis in older overweight and obese men.

BACKGROUND: Increased physical activity is inversely related to the risk to develop cardiovascular disease (CVD). In a recent systematic review, it was reported that CVD patients had an increased cholesterol absorption and a decreased synthesis as compared with control participants. As increased physical activity levels reduce CVD risk, we hypothesized that exercise training will reduce cholesterol absorption and increase endogenous cholesterol synthesis in older overweight and obese men. METHODS: A randomized, controlled, crossover trial was performed. Seventeen apparently healthy older overweight and obese men were randomized to start with an aerobic exercise or no-exercise control period for 8 weeks, separated by 12 weeks washout. Fasting serum total cholesterol (TC) and non-cholesterol sterol concentrations were measured at baseline, and after 4 and 8 weeks. RESULTS: The aerobic exercise program did not affect serum TC concentrations. In addition, exercise did not affect TC-standardized serum concentrations of sitosterol and cholestanol that are markers for cholesterol absorption. However, a trend for reduced TC-standardized campesterol concentrations, which is another validated marker for cholesterol absorption, was observed as compared with control. Lathosterol concentrations, reflecting cholesterol synthesis, did not differ between both periods. CONCLUSIONS: Aerobic exercise training for 8 weeks did not lower serum TC concentrations in older overweight and obese men, but a trend towards a decrease in the cholesterol absorption marker campesterol was found. The cholesterol synthesis marker lathosterol did not change. TRIAL REGISTRATION: posted on www.clinicaltrials.gov as NCT03272061 on 7 September 2017.

Successful management of the first reported case in Austria of COVID-19 with ARDS.

We report the successful management of a patient with severe respiratory failure due to COVID-19 admitted to an intensive care unit complicated by secondary catheter-related infection of Candida glabrata. We are discussing some of the clinical challenges and the pitfalls in molecular diagnosis of SARS-CoV-2, including the fact that a positive PCR result may not always reflect infectiousness.

Absence of herb-drug interactions of mistletoe with the tamoxifen metabolite (E/Z)-endoxifen and cytochrome P450 3A4/5 and 2D6 in vitro.

BACKGROUND: Women diagnosed with breast cancer frequently seek complementary and alternative (CAM) treatment options that can help to cope with their disease and the side effects of conventional cancer therapy. Especially in Europe, breast cancer patients use herbal products containing mistletoe (Viscum album L.). The oldest and one of the most prescribed conventional drugs for the treatment of estrogen receptor positive breast cancer is tamoxifen. Aside from positive clinical experience with the combination of tamoxifen and mistletoe, little is known about possible herb-drug interactions (HDIs) between the two products. In the present in vitro study, we investigated the effect of standardized commercial mistletoe preparations on the activity of endoxifen, the major active metabolite of tamoxifen. METHODS: The estrogen receptor positive human breast carcinoma cell line MCF-7 was treated with (E/Z)-endoxifen hydrochloride in the presence and absence of a defined estradiol concentration. Each concentration of the drug was combined with fermented Viscum album L. extracts (VAE) at clinically relevant doses, and proliferation, apoptosis and cell cycle were analyzed. In parallel, possible inhibition of CYP3A4/5 and CYP2D6 was investigated using 50-donor mixed gender pooled human liver microsomes (HLMs). RESULTS: VAE did not inhibit endoxifen induced cytostasis and cytotoxicity. At higher concentrations, VAE showed an additive inhibitory effect. VAE preparations did not cause inhibition of CYP3A4/5 and CYP2D6 catalyzed tamoxifen metabolism. CONCLUSIONS: The in vitro results suggest that mistletoe preparations can be used in combination with tamoxifen without the risk of HDIs.

Interaction of a standardized mistletoe (Viscum album) preparation with antitumor effects of Trastuzumab in vitro.

BACKGROUND: Besides conventional anticancer therapy many breast cancer patients use complementary and alternative medicine (CAM) like the medicinal herb mistletoe (Viscum album L.). To gain more knowledge about possible herb-drug interactions between CAM and conventional anticancer medications, in the present in vitro study we investigated the effect of a standardized mistletoe preparation on the action of Trastuzumab, a drug used for the treatment of Her-2 positive breast cancer. METHODS: The Her-2 positive human breast carcinoma cell line SK-BR-3 was treated with Trastuzumab. Different doses of the drug were combined with Viscum album extract (VAE) in clinically relevant doses. Proliferation, apoptosis, cell cycle and the secretion of vascular endothelial growth factor (VEGF) were analyzed. RESULTS: No inhibition of antitumor efficacy of Trastuzumab by VAE was detected. VAE and Trastuzumab, either alone or in combination, inhibited proliferation of SK-BR-3 cells in vitro. At higher concentrations VAE induced apoptosis, which was not observed for Trastuzumab. Cells treated with Trastuzumab underwent a G0/G1 cell cycle arrest and cells treated with VAE a G2/M arrest. After application of the two drugs in combination both G0/G1 and G2/M arrest was observed. VEGF secretion of SK-BR-3 cells was significantly inhibited by sole treatment with Trastuzumab or VAE. Combined treatment of Trastuzumab and VAE at clinically relevant doses showed additive inhibitory effects on VEGF secretion. CONCLUSIONS: VAE did not interfere with cytostatic effects of Trastuzumab on SK-BR-3 cells in vitro. Our in vitro results suggest that no risk of safety by herb drug interactions has to be expected from the exposition of cancer cells to Trastuzumab and VAE simultaneously. In contrast, VAE and Trastuzumab seem to exhibit complementary anti-cancer effects in vitro.

Precautionary allergen labelling: perspectives from key stakeholder groups.

Precautionary allergen labelling (PAL) was introduced by the food industry to help manage and communicate the possibility of reaction from the unintended presence of allergens in foods. However, in its current form, PAL is counterproductive for consumers with food allergies. This review aims to summarize the perspectives of all the key stakeholders (including clinicians, patients, food industry and regulators), with the aim of defining common health protection and risk minimization goals. The lack of agreed reference doses has resulted in inconsistent application of PAL by the food industry and in levels of contamination that prompt withdrawal action by enforcement officers. So there is a poor relationship between the presence or absence of PAL and actual reaction risk. This has led to a loss of trust in PAL, reducing the ability of consumers with food allergies to make informed choices. The result has been reduced avoidance, reduced quality of life and increased risk-taking by consumers who often ignore PAL. All contributing stakeholders agree that PAL must reflect actual risk. PAL should be transparent and consistent with rules underpinning decision-making process being communicated clearly to all stakeholders. The use of PAL should indicate the possible, unintended presence of an allergen in a consumed portion of a food product at or above any proposed action level. This will require combined work by all stakeholders to ensure everyone understands the approach and its limitations. Consumers with food allergy then need to be educated to undertake individualized risk assessments in relation to any PAL present.

Adapting livestock management to spatio-temporal heterogeneity in semi-arid rangelands.

Management strategies in rotational grazing systems differ in their level of complexity and adaptivity. Different components of such grazing strategies are expected to allow for adaptation to environmental heterogeneities in space and time. However, most models investigating general principles of rangeland management strategies neglect spatio-temporal system properties including seasonality and spatial heterogeneity of environmental variables. We developed an ecological-economic rangeland model that combines a spatially explicit farm structure with intra-annual time steps. This allows investigating different management components in rotational grazing systems (including stocking and rotation rules) and evaluating their effect on the ecological and economic states of semi-arid grazing systems. Our results show that adaptive stocking is less sensitive to overstocking compared to a constant stocking strategy. Furthermore, the rotation rule becomes important only at stocking numbers that maximize expected income. Altogether, the best of the tested strategies is adaptive stocking combined with a rotation that adapts to both spatial forage availability and seasonality. This management strategy maximises mean income and at the same time maintains the rangeland in a viable condition. However, we could also show that inappropriate adaptation that neglects seasonality even leads to deterioration. Rangelands characterised by higher inter-annual climate variability show a higher risk of income losses under a non-adaptive stocking rule, and non-adaptive rotation is least able to buffer increasing climate variability. Overall, all important system properties including seasonality and spatial heterogeneity of available resources need to be considered when designing an appropriate rangeland management system. Resulting adaptive rotational grazing strategies can be valuable for improving management and mitigating income risks.

Intravenous sildenafil i.v. as rescue treatment for refractory pulmonary hypertension in extremely preterm infants.

BACKGROUND: Intravenous sildenafil treatment has recently shown promising results and good tolerability in the treatment of refractory pulmonary hypertension (PH) in term and near-term neonates, while comparable data in preterm infants are still lacking. However, for critically ill preterm infants suffering from PH refractory to conventional treatment, sildenafil may represent a last treatment resort. PATIENTS AND METHODS: We reviewed the records of 6 critically ill extremely preterm infants who had suffered from PH refractory to conventional treatment and had obtained intravenous sildenafil after careful consideration as ultima ratio treatment. AIM: To describe the responses to sildenafil in terms of hemodynamic and respiratory changes during treatment and outcome. RESULTS: 4/6 patients showed resolution of severe PH with full reversal of ductal shunt direction into pure left-to-right shunt within 82 ± 35 h after sildenafil start. Remarkably, 2/6 patients developed pulmonary hemorrhage at a time point when significant improvement of PH had already taken place, both of them survived. Overall 4/6 patients died, two deaths were related to treatment-refractory PH. CONCLUSION: Intravenous sildenafil treatment seems effective in improving severe PH and hemodynamic instability in extremely preterm infants with refractory PH. Pulmonary hemorrhage may represent a distinct adverse effect of sildenafil treatment in these patients, presumably due to sudden reversal of ductal shunt. Accordingly, sildenafil should be restricted to most severe and refractory cases in this population.

The impact of rapid palatal expansion on children's general health: a literature review.

AIM: The original indication for rapid palatal expansion was to treat skeletal maxillary constriction. As positive effects were clinically proven, the number of indications for rapid palatal expansion has continuously grown. The purpose of the present article was to review the literature and to evaluate the effect of rapid palatal expansion on nose breathing, natural head position, obstructive sleep apnoea syndrome, nocturnal enuresis and conductive hearing loss. CONCLUSION: It can be concluded that rapid palatal expansion is predominantly recommended in children with maxillary constriction. In those with normal occlusion, maxillary expansion can be considered as the really last choice of treatment when other treatment options in patients with nose breathing, obstructive sleep apnea syndrome (OSAS), nocturnal enuresis and conductive hearing loss (CHL) have failed. Therefore, collaboration between paediatricians, otolaryngologists, paediatric dentists and orthodontists will lead to the best treatment outcomes in the future.

The influence of HPMC viscosity as FRC parameter on the release of low soluble drug from hydrophylic matrix tablets.

The importance of functionality-related characteristics (FRC) of hydroxypropyl methylcellulose (HPMC) described in the pharmacopeia monograph can be evaluated only for selected formulation or technological process. The aim of our work was to investigate the influence of apparent viscosity as one of the FRC for two batches of the same HPMC grade on the release properties of diclofenac sodium from HPMC matrix tablets. Our results show that two batches of HPMC differ in viscosity significantly and as a consequence, the significant differences were observed in the release profiles as well. HPMC-B sample has higher viscosity and therefore higher average molecular weight, thus the erosion and drug release were slower compared to HPMC-A sample with lower apparent viscosity. It can be concluded that batch-to-batch viscosity variation of the same HPMC grade can lead to the different release profiles; therefore the specification limits of some FRC should be postulated during the development of each individual formulation. However, the viscosity interval as FRC can not be generalized, because it is different for different tablet compositions.

Qualitative echocardiography parameters for prediction of pulmonary hypertension.

BACKGROUND: Current guidelines recommend echocardiography as the preferred screening method for pulmonary hypertension (PH). The probability of PH is primarily assessed by estimating the right ventricular systolic pressure while the value of qualitative parameters is uncertain. The aim of our study was to evaluate the diagnostic yield of qualitative and quantitative parameters from routine echocardiography reports for PH diagnosis. METHODS: Consecutive patients with suspected PH who received right heart catheterisation and echocardiography within 2 weeks between April 2003 and September 2008 were retrospectively included. PH was diagnosed by a mean pulmonary artery pressure of ≥ 25 mmHg on right heart catheterisation. Qualitative and quantitative parameters from echocardiography reports were analysed with respect to their predictive value for PH diagnosis. RESULTS: Inclusion criteria were met by 272 patients. Diagnosis of PH was confirmed in 172 and excluded in 100 patients. Qualitative and quantitative information about the right ventricle was available in 93% and 85% of the echocardiography reports respectively. Qualitative descriptions of the right ventricle to be dilated predicted PH with sensitivity, specificity, negative and positive predictive value of 89%, 63%, 78% and 80% respectively. An estimated right ventricular systolic pressure of ≥ 50 mmHg on echocardiography predicted PH with sensitivity, specificity, negative and positive predictive value of 84%, 69%, 68% and 84% respectively. CONCLUSION: Qualitative parameters are frequently described in routine echocardiography reports and are valuable for the prediction of PH with a similar diagnostic accuracy as the estimation of right ventricular systolic pressure.

Development of a biocrystallisation assay for examining effects of homeopathic preparations using cress seedlings.

A major challenge in basic research into homeopathic potentisation is to develop bioassays that yield consistent results. We evaluated the potential of a seedling-biocrystallisation method. Cress seeds (Lepidium sativum L.) germinated and grew for 4 days in vitro in Stannum metallicum 30x or water 30x in blinded and randomized assignment. 15 experiments were performed at two laboratories. CuCl(2)-biocrystallisation of seedlings extracted in the homeopathic preparations was performed on circular glass plates. Resulting biocrystallograms were analysed by computerized textural image analysis. All texture analysis variables analysed yielded significant results for the homeopathic treatment; thus the texture of the biocrystallograms of homeopathically treated cress exhibited specific characteristics. Two texture analysis variables yielded differences between the internal replicates, most probably due to a processing order effect. There were only minor differences between the results of the two laboratories. The biocrystallisation method seems to be a promising complementary outcome measure for plant bioassays investigating effects of homeopathic preparations.

Plasma oxyphytosterols most likely originate from hepatic oxidation and subsequent spill-over in the circulation.

We evaluated oxyphytosterol (OPS) concentrations in plasma and various tissues of two genetically modified mouse models with either increased cholesterol (apoE KO mice) or increased cholesterol and plant sterol (PS) concentrations (apoExABCG8 dKO mice). Sixteen female apoE KO and 16 dKO mice followed the same standard, low OPS-chow diet. Animals were euthanized at 36 weeks to measure PS and OPS concentrations in plasma, brain, liver and aortic tissue. Cholesterol and oxysterol (OS) concentrations were analyzed as reference for sterol oxidation in general. Plasma campesterol (24.1 ± 4.3 vs. 11.8 ± 3.0 mg/dL) and sitosterol (67.4 ± 12.7 vs. 4.9 ± 1.1 mg/dL) concentrations were severely elevated in the dKO compared to the apoE KO mice (p < 0.001). Also, in aortic and brain tissue, PS levels were significantly elevated in dKO. However, plasma, aortic and brain OPS concentrations were comparable or even lower in the dKO mice. In contrast, in liver tissue, both PS and OPS concentrations were severely elevated in the dKO compared to apoE KO mice (sum OPS: 7.4 ± 1.6 vs. 4.1 ± 0.8 ng/mg, p < 0.001). OS concentrations followed cholesterol concentrations in plasma and all tissues suggesting ubiquitous oxidation. Despite severely elevated PS concentrations, OPS concentrations were only elevated in liver tissue, suggesting that OPS are primarily formed in the liver and plasma concentrations originate from hepatic spill-over into the circulation.

Conserved function of the Krüppel gap gene in the blowfly Lucilia sericata, despite anterior shift of expression.

To determine whether expression patterns of segmentation genes found in Drosophila melanogaster can be scaled to pattern larger insects, we studied the expression of the Krüppel (Kr) gene in the blowfly Lucilia sericata. Compared with Drosophila Kr, L. sericata Kr showed an unexpected 10% shift of expression towards the anterior pole. Furthermore, expression domains not found in D. melanogaster were present at the blastoderm stage of L. sericata. To compare Kr activity and function, we employed RNA interference-mediated gene silencing. We found Kr phenotypes in L. sericata comparable with those observed in D. melanogaster, demonstrating that L. sericata Kr functions as a gap gene as it does in Drosophila. Our results show that, despite an anterior shift in expression, Kr function has remained conserved during the evolution of the blowflies.

Optimization of nanowire DNA sensor sensitivity using self-consistent simulation.

In order to facilitate the rational design and the characterization of nanowire field-effect sensors, we have developed a model based on self-consistent charge-transport equations combined with interface conditions for the description of the biofunctionalized surface layer at the semiconductor/electrolyte interface. Crucial processes at the interface, such as the screening of the partial charges of the DNA strands and the influence of the angle of the DNA strands with respect to the nanowire, are computed by a Metropolis Monte Carlo algorithm for charged molecules at interfaces. In order to investigate the sensing mechanism of the device, we have computed the current­voltage characteristics, the electrostatic potential and the concentrations of electrons and holes. Very good agreement with measurements has been found and optimal device parameters have been identified. Our approach provides the capability to study the device sensitivity, which is of fundamental importance for reliable sensing.

Reporting experiments in homeopathic basic research-description of the checklist development.

The objective of this study was to develop a criteria catalogue serving as a guideline for authors to improve quality of reporting experiments in basic research in homeopathy. A Delphi Process was initiated including three rounds of adjusting and phrasing plus two consensus conferences. European researchers who published experimental work within the last 5 years were involved. A checklist for authors provide a catalogue with 23 criteria. The "Introduction" should focus on underlying hypotheses, the homeopathic principle investigated and state if experiments are exploratory or confirmatory. "Materials and methods" should comprise information on object of investigation, experimental setup, parameters, intervention and statistical methods. A more detailed description on the homeopathic substances, for example, manufacture, dilution method, starting point of dilution is required. A further result of the Delphi process is to raise scientists' awareness of reporting blinding, allocation, replication, quality control and system performance controls. The part "Results" should provide the exact number of treated units per setting which were included in each analysis and state missing samples and drop outs. Results presented in tables and figures are as important as appropriate measures of effect size, uncertainty and probability. "Discussion" in a report should depict more than a general interpretation of results in the context of current evidence but also limitations and an appraisal of aptitude for the chosen experimental model. Authors of homeopathic basic research publications are encouraged to apply our checklist when preparing their manuscripts. Feedback is encouraged on applicability, strength and limitations of the list to enable future revisions.

Analysis of uveitis rates across all etanercept ankylosing spondylitis clinical trials.

OBJECTIVE: To assess uveitis (including iritis and iridocyclitis) incidence from clinical trials of etanercept in patients with ankylosing spondylitis (AS). METHODS: Clinical trials of etanercept in AS (four placebo-controlled; one active-controlled; three open-label) were examined for reports of uveitis. Between-group differences with confidence intervals (CIs) in the uveitis rates were calculated for the double-blind, active-controlled and long-term studies. RESULTS: In placebo-controlled trials, the uveitis rate per 100 subject years (95% CI) for etanercept (8.6 (4.5 to 14.2)) was lower than that for placebo (19.3 (11.0 to 29.8), p = 0.03). In the active comparator trial, rates for etanercept and sulfasalazine were similar (10.7 (5.5 to 17.6) and 14.7 (6.4 to 26.5), respectively; p = 0.49). The long-term rate for etanercept, estimated from both placebo-controlled and open-label extension studies was 12.0 (10.0 to 14.1). CONCLUSIONS: In subjects with AS, rates of uveitis events with etanercept were lower than with placebo in placebo-controlled trials and similar to sulfasalazine in an active comparator trial.

Interactions of biopolymers carrageenans with cationic drug doxazosin mesylate characterized by means of differential scanning calorimetry.

When ionic polymers (polyelectrolytes) are used as excipients in pharmaceutical formulations, the properties of oppositely charged drugs may be strongly affected by the charge-charge interactions or complex formation. Usually these effects are considered as a negative event resulting in a drug-excipient incompatibility. Sometimes ionic interactions are preferred to prolong drug release from dosage forms in a controllable manner. Ionic interactions of carrageenans with doxazosin mesylate were confirmed by differential scanning calorimetry (DSC). Evident peak shifts and shape changes of assumed desulfation peak of carrageenans in concordance with disappearance of melting peak of doxazosin mesylate (DM) in DSC curves were obtained. The range of thermal effects is depended on the ratio of doxazosin mesylate and carrageenans. The higher the ratio of DM compared to CARRs the more evident are the interactions.