Plausibility of Menstrual Cycle Apps Claiming to Support Conception.

The interval of peak fertility during the menstrual cycle is of limited duration, and the day of ovulation varies, even in women with fairly regular cycles. Therefore, menstrual cycle apps identifying the "fertile window" for women trying to conceive must be quite precise. A deviation of a few days may lead the couple to focus on less- or non-fertile days for sexual intercourse and thus may be worse than random intercourse. The aim of the present investigation was to develop a scoring system for rating available apps for determining the fertile window and secondarily pilot test 12 apps currently available in both German and English (consisting of 6 calendar-based apps: Clue Menstruations- und Zykluskalender, Flo Menstruationskalender, Maya-Mein Periodentracker, Menstruationskalender Pro, Period Tracker Deluxe, and WomanLog-Pro-Kalender; 2 calculothermal apps: Ovy and Natural Cycles; and 4 symptothermal apps: myNFP, Lady Cycle, Lily, and OvuView). The calendar-based apps were investigated by entering several series of cycles with varying lengths, whereas the symptom-based apps were examined by entering data of cycles with known temperature rise, cervical mucus pattern, and clinical ovulation. The main criteria for evaluating the cycle apps were as follows: (1) What methods/parameters were used to determine the fertile window? (2) What study results exist concerning that underlying method/parameters? (3) What study results exist concerning the app itself? (4) Was there a qualified counseling service? The calendar-based apps predicted the fertile days based on data of previous cycles. They obtained zero points in our scoring system, as they did not comply with any of the evaluated criteria. Calculothermal apps had similar deficits for predicting the most fertile days and produced suboptimal results (Ovy 3/30 points and Natural Cycles 2/30 points). The symptothermal apps determined the fertile days based on parameters of the current cycle: Lady Cycle scored 20/30 points, myNFP 20/30 points, Lily 19/30 points, and OvuView 11/30 points. We concluded that the available cycle apps vary according to their underlying scientific quality and clear rating criteria have been suggested. Three of the tested apps were judged to be eligible for further study. The scientific evaluation of cycle apps depends on good prospective studies undertaken by independent investigators who are free of commercial bias.

Factors associated with efficacy of an ibuprofen/pseudoephedrine combination drug in pharmacy customers with common cold symptoms.

AIM: The aim of this study was to explore factors affecting efficacy of treatment of common cold symptoms with an over-the-counter ibuprofen/pseudoephedrine combination product. METHODS: Data from an anonymous survey among 1770 pharmacy customers purchasing the combination product for treatment of own common cold symptoms underwent post-hoc descriptive analysis. Scores of symptoms typically responsive to ibuprofen (headache, pharyngeal pain, joint pain and fever), typically responsive to pseudoephedrine (congested nose, congested sinus and runny nose), considered non-specific (sneezing, fatigue, dry cough, cough with expectoration) and comprising all 11 symptoms were analysed. Multiple regression analysis was applied to explore factors associated with greater reduction in symptom intensity or greater probability of experiencing a symptom reduction of at least 50%. RESULTS: After intake of first dose of medication, typically ibuprofen-sensitive, pseudoephedrine-responsive, non-specific and total symptoms were reduced by 60.0%, 46.3%, 45.4% and 52.8%, respectively. A symptom reduction of at least 50% was reported by 73.6%, 55.1%, 50.9% and 61.6% of participants, respectively. A high baseline score was associated with greater reductions in symptom scores but smaller probability of achieving an improvement of at least 50%. Across both multiple regression approaches, two tablets at first dosing were more effective than one and (except for ibuprofen-sensitive symptoms) starting treatment later than day 2 of the cold was generally less effective. DISCUSSION AND CONCLUSIONS: Efficacy of an ibuprofen/pseudoephedrine combination in the treatment of common cold symptoms was dose-dependent and greatest when treatment started within the first 2 days after onset of symptoms.

Pathophysiological Factors in the Relationship between Chronological Age and Calculated Lung Age as Detected in a Screening Setting in Community-Dwelling Subjects.

AIM: To explore the relationship between pathophysiological factors and premature lung aging in a cohort of community-dwelling subjects in a health-screening setting. METHODS: 16,107 pharmacy customers in Germany (5954 males, 10,153 females; mean age 59.7 years) participated in a lung function screening project by providing demographic data, including smoking status and known airway conditions and performing spirometry with a Vitalograph, a spirometry screening device. Lung age was calculated from the spirometric findings, and the difference between chronological age and calculated lung age was analyzed in its relationship to the demographic data in general linear models. RESULTS: In the overall cohort, calculated lung age exceeded chronological age by 10.0 years. Based on the subset of non-smokers not reporting any airway conditions, Vitalograph data in this setting may underestimate FEV1 to some degree, but this apparently had little impact on the detection of association of lung age with pathophysiological factors or the corresponding effect sizes. The most important factors associated with greater lung age based on strength of association were presence of dyspnea, being a smoker, and reporting a history of COPD or asthma. Corresponding effect sizes for the difference between age and lung age were 6.5, 5.7, 13.9, and 8.3 years over the chronological age. DISCUSSION AND CONCLUSION: These data confirm the usefulness of screening devices of lung function testing for epidemiological but potentially also for pharmaco-epidemiological studies.

[Drugs in chronic venous insufficiency--the challenge of demonstrating clinical efficacy]. / Der Nachweis der klinischen Wirksamkeit von Odemprotektiva und seine Tücken.

Approximately 90% of German adults show alterations of their lower limb veins; about every fifth suffers from symptoms of chronic venous insufficiency (CVI). With compression therapy showing low compliance, CVI oedemas and accompanying subjective symptoms are frequently treated with anti-oedematous drugs of herbal origin. A guideline outlines the requirements for clinical studies with CVI drugs. Water displacement plethysmometry (volumetry) is the gold standard for determining the reduction ofoedemas. Besides reducing oedemas, drugs should also demonstrate effects on accompanying symptoms influencing quality of life. Despite assistance provided by the guideline, clinical studies in CVI are complex and subject to multiple error sources in planning and execution. The corroboration of successful studies in further confirmatory studies is good practice and demanded by regulatory authorities. This practice reduces the risk of drugs being accepted as effective just based on the play of chance. As an example, placebo controlled studies with an extract from red vine leaves show that a careful definition of patients as well as meticulous study planning and execution can reproducibly verify significant and clinically relevant treatment effects. When evaluating clinical studies it is recommended to refer to the CONSORT statement. Publications missing certain minimum information make interpretation difficult and may result in a biased judgment of the effects of therapy.

Peripheral mitochondrial dysfunction in Alzheimer's disease: focus on lymphocytes.

Alzheimer's disease (AD) is the most common progressive neurodegenerative disease. Today, AD affects millions of people worldwide and the number of AD cases will increase with increased life expectancy. The AD brain is marked by severe neurodegeneration like the loss of synapses and neurons, atrophy and depletion of neurotransmitter systems in the hippocampus and cerebral cortex. Recent findings suggest that these pathological changes are causally induced by mitochondrial dysfunction and increased oxidative stress. These changes are not only observed in the brain of AD patients but also in the periphery. In this review, we discuss the potential role of elevated apoptosis, increased oxidative stress and especially mitochondrial dysfunction as peripheral markers for the detection of AD in blood cells especially in lymphocytes. We discuss recent not otherwise published findings on the level of complex activities of the respiratory chain comprising mitochondrial respiration and the mitochondrial membrane potential (MMP). We obtained decreased basal MMP levels in lymphocytes from AD patients as well as enhanced sensitivity to different complex inhibitors of the respiratory chain. These changes are in line with mitochondrial defects obtained in AD cell and animal models, and in post-mortem AD tissue. Importantly, these mitochondrial alterations where not only found in AD patients but also in patients with mild cognitive impairment (MCI). These new findings point to a relevance of mitochondrial function as an early peripheral marker for the detection of AD and MCI.

Mitochondrion-derived reactive oxygen species lead to enhanced amyloid beta formation.

AIMS: Intracellular amyloid beta (Aß) oligomers and extracellular Aß plaques are key players in the progression of sporadic Alzheimer's disease (AD). Still, the molecular signals triggering Aß production are largely unclear. We asked whether mitochondrion-derived reactive oxygen species (ROS) are sufficient to increase Aß generation and thereby initiate a vicious cycle further impairing mitochondrial function. RESULTS: Complex I and III dysfunction was induced in a cell model using the respiratory inhibitors rotenone and antimycin, resulting in mitochondrial dysfunction and enhanced ROS levels. Both treatments lead to elevated levels of Aß. Presence of an antioxidant rescued mitochondrial function and reduced formation of Aß, demonstrating that the observed effects depended on ROS. Conversely, cells overproducing Aß showed impairment of mitochondrial function such as comprised mitochondrial respiration, strongly altered morphology, and reduced intracellular mobility of mitochondria. Again, the capability of these cells to generate Aß was partly reduced by an antioxidant, indicating that Aß formation was also ROS dependent. Moreover, mice with a genetic defect in complex I, or AD mice treated with a complex I inhibitor, showed enhanced Aß levels in vivo. INNOVATION: We show for the first time that mitochondrion-derived ROS are sufficient to trigger Aß production in vitro and in vivo. CONCLUSION: Several lines of evidence show that mitochondrion-derived ROS result in enhanced amyloidogenic amyloid precursor protein processing, and that Aß itself leads to mitochondrial dysfunction and increased ROS levels. We propose that starting from mitochondrial dysfunction a vicious cycle is triggered that contributes to the pathogenesis of sporadic AD.

The interaction of beta-amyloid protein with cellular membranes stimulates its own production.

Gradual changes in steady-state levels of beta amyloid peptides (Abeta) in brain are considered an initial step in the amyloid cascade hypothesis of Alzheimer's disease. Abeta is a product of the secretase cleavage of amyloid precursor protein (APP). There is evidence that the membrane lipid environment may modulate secretase activity and alters its function. Cleavage of APP strongly depends on membrane properties. Since Abeta perturbs cell membrane fluidity, the cell membrane may be the location where the neurotoxic cascade of Abeta is initiated. Therefore, we tested effects of oligomeric Abeta on membrane fluidity of whole living cells, the impact of exogenous and cellular Abeta on the processing of APP and the role of GM-1 ganglioside. We present evidence that oligoAbeta((1-40)) stimulates the amyloidogenic processing of APP by reducing membrane fluidity and complexing with GM-1 ganglioside. This dynamic action of Abeta may start a vicious circle, where endogenous Abeta stimulates its own production. Based on our novel findings, we propose that oligoAbeta((1-40)) accelerates the proteolytic cleavage of APP by decreasing membrane fluidity.