Time to Pregnancy for Women Using a Fertility Awareness Based Mobile Application to Plan a Pregnancy

Background: Time to pregnancy (TTP) is a biomarker of fecundability and has been associated with behavioral and environmental characteristics; however, these associations have not been examined in a large population-based sample of application (app) users. Materials and Methods: This observational study followed 5,376 women with an age range of 18 to 45 years who used an app to identify their fertile window. We included women who started trying to conceive between September 30, 2017 and August 31, 2018. TTP was calculated as the number of menstrual cycles from when the user switched to "Plan" mode up to and including the cycle in which they logged a positive pregnancy test. We examined associations with several characteristics, including age, gravidity, body mass index, cycle length and cycle length variation, frequency of sexual intercourse, and temperature measuring frequency. Discrete time fecundability models were used to estimate fecundability odds ratios. Results: For the complete cohort the 6-cycle and 12-cycle cumulative pregnancy probabilities were found to be 61% (95% confidence interval [CI]: 59-62) and 74% (95% CI: 73-76), respectively. The median TTP was four cycles. The highest fecundability was associated with an age of less than 35 years, with cycle length variation <5 days and logging sexual intercourse on at least 20% of days added (the proportion of days in which intercourse was logged) (11.5% [n = 613] of entire sample). This group achieved a 6- and 12-cycle cumulative pregnancy probability of 88% (95% CI: 85-91) and 95% (95% CI: 94-97), respectively, and a TTP of 2 cycles. Conclusions: Natural Cycles was an effective method of identifying the fertile window and a noninvasive educational option for women planning a pregnancy. Women under age 35 with regular cycles showed a high pregnancy rate

Role of the PAS sensor domains in the Bacillus subtilis sporulation kinase KinA

Histidine kinases are sophisticated molecular sensors that are used by bacteria to detect and respond to a multitude of environmental signals. KinA is the major histidine kinase required for initiation of sporulation upon nutrient deprivation in Bacillus subtilis. KinA has a large N-terminal region (residues 1 to 382) that is uniquely composed of three tandem Per-ARNT-Sim (PAS) domains that have been proposed to constitute a sensor module. To further enhance our understanding of this "sensor" region, we defined the boundaries that give rise to the minimal autonomously folded PAS domains and analyzed their homo- and heteroassociation properties using analytical ultracentrifugation, nuclear magnetic resonance (NMR) spectroscopy, and multiangle laser light scattering. We show that PAS(A) self-associates very weakly, while PAS(C) is primarily a monomer. In contrast, PAS(B) forms a stable dimer (K-d [dissociation constant] o

Efficacy of thalidomide in a girl with inflammatory calcinosis, a severe complication of juvenile dermatomyositis

We report a 14-year-old girl with juvenile dermatomyositis (JDM) complicated by severe inflammatory calcinosis successfully treated with thalidomide. She was diagnosed as JDM when she was 4 years old after a few months of increasing lethargy, muscle pain, muscle weakness, and rash. During three months, clinical manifestations and abnormal laboratory findings were effectively treated with oral prednisolone. However, calcinosis was recognized 18 months after disease onset. Generalized calcinosis rapidly progressed with high fever, multiple skin/subcutaneous inflammatory lesions, and increased level of CRP. Fifty mg/day (1.3 mg/kg day) of oral thalidomide was given for the first four weeks, and then the dose was increased to 75 mg/day. Clinical manifestations subsided, and inflammatory markers had clearly improved. Frequent high fever and local severe pain with calcinosis were suppressed. The levels of FDP-E, IgG, and tryglyceride, which were all elevated before the thalidomide treatment, were gradually returned to the normal range. Over the 18 months of observation up to the present, she has had no inflammatory calcinosis, or needed any hospitalization, although established calcium deposits still remain. Her condition became painless, less extensive and less inflammatory with the CRP level below 3.08 mg/dL. Recent examination by whole-body 18F-FDG-PET-CT over the 15 months of thalidomide treatment demonstrated fewer hot spots around the subcutaneous calcified lesions

Exploiting unexpected situations in the mathematics classroom

The professional development of mathematics teachers needs to support teachers in orchestrating the mathematics classroom in ways that enable them to respond flexibly and productively to the unexpected. When a situation arises in the classroom which is not connected in an obvious way to the mathematical learning intentions of the lesson, it can be challenging for the teacher to improvise so as to craft this situation into an opportunity for doing and learning mathematics. In this study, as teacher-researcher I maintained a record of unexpected situations as they arose in my own secondary mathematics classroom. Details are given of four unexpected situations which I found ways to exploit mathematically, and these are analysed to highlight factors which may enhance a mathematics teacher’s preparedness for dealing with the unexpected. The results of this study indicate that deviating from the intended lesson to exploit an unexpected situation in which students have shown some interest can lead them into enjoyable and worthwhile mathematical engagement

Indoor Residual Spraying in Combination with Insecticide-Treated Nets Compared to Insecticide-Treated Nets Alone for Protection against Malaria: A Cluster Randomised Trial in Tanzania.

Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) of houses provide effective malaria transmission control. There is conflicting evidence about whether it is more beneficial to provide both interventions in combination. A cluster randomised controlled trial was conducted to investigate whether the combination provides added protection compared to ITNs alone. In northwest Tanzania, 50 clusters (village areas) were randomly allocated to ITNs only or ITNs and IRS. Dwellings in the ITN+IRS arm were sprayed with two rounds of bendiocarb in 2012. Plasmodium falciparum prevalence rate (PfPR) in children 0.5-14 y old (primary outcome) and anaemia in children <5 y old (secondary outcome) were compared between study arms using three cross-sectional household surveys in 2012. Entomological inoculation rate (secondary outcome) was compared between study arms. IRS coverage was approximately 90%. ITN use ranged from 36% to 50%. In intention-to-treat analysis, mean PfPR was 13% in the ITN+IRS arm and 26% in the ITN only arm, odds ratio = 0.43 (95% CI 0.19-0.97, n = 13,146). The strongest effect was observed in the peak transmission season, 6 mo after the first IRS. Subgroup analysis showed that ITN users were additionally protected if their houses were sprayed. Mean monthly entomological inoculation rate was non-significantly lower in the ITN+IRS arm than in the ITN only arm, rate ratio = 0.17 (95% CI 0.03-1.08). This is the first randomised trial to our knowledge that reports significant added protection from combining IRS and ITNs compared to ITNs alone. The effect is likely to be attributable to IRS providing added protection to ITN users as well as compensating for inadequate ITN use. Policy makers should consider deploying IRS in combination with ITNs to control transmission if local ITN strategies on their own are insufficiently effective. Given the uncertain generalisability of these findings, it would be prudent for malaria control programmes to evaluate the cost-effectiveness of deploying the combination.\ud \u

Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review

<p>Abstract</p> <p>Background</p> <p>Cannabis therapy has been considered an effective treatment for spasticity, although clinical reports of symptom reduction in multiple sclerosis (MS) describe mixed outcomes. Recently introduced therapies of combined Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD) extracts have potential for symptom relief with the possibility of reducing intoxication and other side effects. Although several past reviews have suggested that cannabinoid therapy provides a therapeutic benefit for symptoms of MS, none have presented a methodical investigation of newer cannabinoid treatments in MS-related spasticity. The purpose of the present review was to systematically evaluate the effectiveness of combined THC and CBD extracts on MS-related spasticity in order to increase understanding of the treatment's potential effectiveness, safety and limitations.</p> <p>Methods</p> <p>We reviewed MEDLINE/PubMed, Ovid, and CENTRAL electronic databases for relevant studies using randomized controlled trials. Studies were included only if a combination of THC and CBD extracts was used, and if pre- and post-treatment assessments of spasticity were reported.</p> <p>Results</p> <p>Six studies were systematically reviewed for treatment dosage and duration, objective and subjective measures of spasticity, and reports of adverse events. Although there was variation in the outcome measures reported in these studies, a trend of reduced spasticity in treated patients was noted. Adverse events were reported in each study, however combined TCH and CBD extracts were generally considered to be well-tolerated.</p> <p>Conclusion</p> <p>We found evidence that combined THC and CBD extracts may provide therapeutic benefit for MS spasticity symptoms. Although some objective measures of spasticity noted improvement trends, there were no changes found to be significant in post-treatment assessments. However, subjective assessment of symptom relief did often show significant improvement post-treatment. Differences in assessment measures, reports of adverse events, and dosage levels are discussed.</p

Role of miR-10b in breast cancer metastasis

Ninety percent of cancer-related mortality is caused by metastasis. Current cancer treatments can control many primary tumors but rarely stop the metastatic spread. Accumulating evidence demonstrates that miRNAs are involved in cancer initiation and progression. Furthermore, several miRNAs have been found to regulate metastasis. In particular, recent studies provide the first functional evidence that overexpression of a specific miRNA, miR-10b, can contribute to the development of metastasis, which can be exploited therapeutically in treating breast cancer metastasis in mice. Further in-depth analysis should provide more precise evaluation of the roles, mechanisms, and therapeutic utility of this miRNA in breast cancer

Central nervous system and muscular bundles preserved in a 240 million year old giant bristletail (Archaeognatha: Machilidae)

Among the incomparably diverse group of insects no cases of central nervous system (CNS) preservation have been so far described in compression fossils. A third of the fossil insects collected from a 240-239 million year old (Ma) level at Monte San Giorgio UNESCO World Heritage (SwitzerlandItaly) underwent phosphatization, resulting in the extraordinary preservation of soft tissues. Here we describe Gigamachilis triassicus gen. et sp. nov. (Archaeognatha: Machiloidea: Machilidae) that, with an estimated total length of similar to 80 millimeters, represents the largest apterygote insect ever recorded. The holotype preserves: (i) components of the CNS represented by four abdominal ganglia, optic lobes with neuropils and compound retina;(ii) muscular bundles. Moreover, G. triassicus, possessing morphological features that prompt its assignment to the extant archaeognathan ingroup Machilidae, places the origin of modern lineages to Middle Triassic. Interestingly, at Monte San Giorgio, in the same stratigraphic unit the modern morphology of G. triassicus co-occurs with the ancient one represented by Dasyleptus triassicus (Archaeognatha: dagger Monura). Comparing these two types of body organization we provide a new reconstruction of the possible character evolution leading towards modern archaeognathan forms, suggesting the acquisition of novel features in a lineage of apterygote insects during the Permian or the Lower Triassic

Role of mitochondrial raft-like microdomains in the regulation of cell apoptosis

Lipid rafts are envisaged as lateral assemblies of specific lipids and proteins that dissociate and associate rapidly and form functional clusters in cell membranes. These structural platforms are not confined to the plasma membrane; indeed lipid microdomains are similarly formed at subcellular organelles, which include endoplasmic reticulum, Golgi and mitochondria, named raft-like microdomains. In addition, some components of raft-like microdomains are present within ER-mitochondria associated membranes. This review is focused on the role of mitochondrial raft-like microdomains in the regulation of cell apoptosis, since these microdomains may represent preferential sites where key reactions take place, regulating mitochondria hyperpolarization, fission-associated changes, megapore formation and release of apoptogenic factors. These structural platforms appear to modulate cytoplasmic pathways switching cell fate towards cell survival or death. Main insights on this issue derive from some pathological conditions in which alterations of microdomains structure or function can lead to severe alterations of cell activity and life span. In the light of the role played by raft-like microdomains to integrate apoptotic signals and in regulating mitochondrial dynamics, it is conceivable that these membrane structures may play a role in the mitochondrial alterations observed in some of the most common human neurodegenerative diseases, such as Amyotrophic lateral sclerosis, Huntington's chorea and prion-related diseases. These findings introduce an additional task for identifying new molecular target(s) of pharmacological agents in these pathologies