What women say about their dysmenorrhea: a qualitative thematic analysis

Background Dysmenorrhea is highly prevalent and is the leading cause of absence from school and work among women of reproductive age. Evidence suggests that dysmenorrhea may also be a risk factor for other chronic pain conditions. Limited research has examined women’s experience with dysmenorrhea using qualitative data. Research is warranted to address issues and needs that are important from women’s own perspectives. Therefore, the purpose of this study was to describe women’s salient thoughts about their experiences of dysmenorrhea. Methods We analyzed data collected from an open-ended question within a cross-sectional survey study conducted in the United States. Using qualitative thematic analysis, free text responses to a question asking women to share their experience with dysmenorrhea were analyzed. Results The sample consisted of 225 women who provided valid responses to the open-ended question. Six themes were identified: (1) The dysmenorrhea symptom experience varied among women; (2) The dysmenorrhea symptom experience varied across time, (3) A variety of factors influenced the dysmenorrhea symptom experience, (4) Dysmenorrhea symptoms could have a negative impact on the women’s daily lives, (5) Dysmenorrhea was not seen as a legitimate health issue by the women, health care providers, or society, and (6) Treatment for women with dysmenorrhea varied in acceptability and effectiveness. Conclusions The findings of this study have important implications for dysmenorrhea symptom assessment and the development of personalized interventions to support dysmenorrhea management

Reasons women do not seek health care for dysmenorrhea

Aims and objectives The purpose of this study was to identify and describe reasons women do not seek health care for dysmenorrhea symptoms. Background Although dysmenorrhea is highly prevalent among women, can cause significant disruptions in their daily lives, and may increase their risk for future chronic pain conditions, few women seek health care for dysmenorrhea. A better understanding of why women do not seek health care is necessary to develop strategies that facilitate care seeking and optimal symptom management. Design A Qualitative Descriptive design was used to guide the study and summarize text responses to an open-ended survey question. Methods Participants in an online survey study who had not sought health care for dysmenorrhea (N=509) were asked to write about their reasons for not seeking care. Data were collected in January and February 2015. Participants’ text responses were analyzed using qualitative content analysis. Results Nine categories of reasons were identified: assuming symptoms are normal, preferring to self-manage symptoms, having limited resources, thinking providers would not offer help, being unaware of treatment options, considering symptoms to be tolerable, being wary of available treatments, feeling embarrassed or afraid to seek care, and not seeking health care generally. Conclusions Findings can guide the development of strategies to promote care seeking and inform policy and clinical practice to improve dysmenorrhea management. Relevance to clinical practice Findings underscore the need to provide routine screening for dysmenorrhea, avoid dismissing dysmenorrhea symptoms, initiate discussions and provide education about dysmenorrhea, provide treatments options based on evidence and women's preferences, and raise public awareness of dysmenorrhea and its impact

Quantifying cellular mechanics and adhesion in renal tubular injury using single cell force spectroscopy

Abstract Tubulointerstitial fibrosis represents the major underlying pathology of diabetic nephropathy where loss of cell-to-cell adhesion is a critical step. To date, research has predominantly focussed on the loss of cell surface molecular binding events that include altered protein ligation. In the current study, atomic force microscopy single cell force spectroscopy (AFM- SCFS) was used to quantify changes in cellular stiffness and cell adhesion in TGF-β1 treated kidney cells of the human proximal tubule (HK2). AFM indentation of TGF-β1 treated HK2 cells showed a significant increase (42%) in the Elastic modulus (stiffness) compared to control. Fluorescence microscopy confirmed that increased cell stiffness is accompanied by reorganization of the cytoskeleton. The corresponding changes in stiffness, due to F-actin rearrangement, affected the work of detachment by changing the separation distance between two adherent cells. Overall, our novel data quantitatively demonstrate a correlation between cellular elasticity, adhesion and early morphologic/phenotypic changes associated with tubular injury

Genomic analysis of the function of the transcription factor gata3 during development of the Mammalian inner ear

We have studied the function of the zinc finger transcription factor gata3 in auditory system development by analysing temporal profiles of gene expression during differentiation of conditionally immortal cell lines derived to model specific auditory cell types and developmental stages. We tested and applied a novel probabilistic method called the gamma Model for Oligonucleotide Signals to analyse hybridization signals from Affymetrix oligonucleotide arrays. Expression levels estimated by this method correlated closely (p<0.0001) across a 10-fold range with those measured by quantitative RT-PCR for a sample of 61 different genes. In an unbiased list of 26 genes whose temporal profiles clustered most closely with that of gata3 in all cell lines, 10 were linked to Insulin-like Growth Factor signalling, including the serine/threonine kinase Akt/PKB. Knock-down of gata3 in vitro was associated with a decrease in expression of genes linked to IGF-signalling, including IGF1, IGF2 and several IGF-binding proteins. It also led to a small decrease in protein levels of the serine-threonine kinase Akt2/PKB beta, a dramatic increase in Akt1/PKB alpha protein and relocation of Akt1/PKB alpha from the nucleus to the cytoplasm. The cyclin-dependent kinase inhibitor p27(kip1), a known target of PKB/Akt, simultaneously decreased. In heterozygous gata3 null mice the expression of gata3 correlated with high levels of activated Akt/PKB. This functional relationship could explain the diverse function of gata3 during development, the hearing loss associated with gata3 heterozygous null mice and the broader symptoms of human patients with Hearing-Deafness-Renal anomaly syndrome

Temperature insensitive refractometer using core and cladding modes in open-top ridge waveguide

In order to overcome the well-known limitation of temperature instability in Bragg grating waveguide sensors, a temperature insensitive open-top ridge waveguide refractometer is developed by using a cladding mode resonance as a temperature reference. The relative shift of the core mode resonance to cladding mode resonance is used to measure the refractive index of substances under test. Specifically, the device fabricated here produces a relative resonance shift of 1 pm for every 5 × 10-4 of measured index change, with a temperature sensitivity ∼ 0.5 pm/°C

Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.

Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells

\emph{In-situ} determination of astro-comb calibrator lines to better than 10 cm s−1^{-1}

Improved wavelength calibrators for high-resolution astrophysical spectrographs will be essential for precision radial velocity (RV) detection of Earth-like exoplanets and direct observation of cosmological deceleration. The astro-comb is a combination of an octave-spanning femtosecond laser frequency comb and a Fabry-P\'erot cavity used to achieve calibrator line spacings that can be resolved by an astrophysical spectrograph. Systematic spectral shifts associated with the cavity can be 0.1-1 MHz, corresponding to RV errors of 10-100 cm/s, due to the dispersive properties of the cavity mirrors over broad spectral widths. Although these systematic shifts are very stable, their correction is crucial to high accuracy astrophysical spectroscopy. Here, we demonstrate an \emph{in-situ} technique to determine the systematic shifts of astro-comb lines due to finite Fabry-P\'erot cavity dispersion. The technique is practical for implementation at a telescope-based spectrograph to enable wavelength calibration accuracy better than 10 cm/s.Comment: 11 pages, 7 figure

Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms

Cancer cells depend on transcription of telomerase reverse transcriptase (TERT). Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3′-oxime (BIO) predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several aspects of TERT regulation including previously unknown mechanisms. An extrapolation suggests that a dominant stimulatory system may programme TERT for transcriptional stability

Polymorphisms in the selectin gene cluster are associated with fertility and survival time in a population of Holstein Friesian cows

Selectins are adhesion molecules, which mediate attachment between leucocytes and endothelium. They aid extravasation of leucocytes from blood into inflamed tissue during the mammary gland’s response to infection. Selectins are also involved in attachment of the conceptus to the endometrium and subsequent placental development. Poor fertility and udder health are major causes for culling dairy cows. The three identified bovine selectin genes SELP, SELL and SELE are located in a gene cluster. SELP is the most polymorphic of these genes. Several SNP in SELP and SELE are associated with human vascular disease, while SELP SNP rs6127 has been associated with recurrent pregnancy loss in women. This study describes the results of a gene association study for SNP in SELP (n = 5), SELL (n = 2) and SELE (n = 1) with fertility, milk production and longevity traits in a population of 337 Holstein Friesian dairy cows. Blood samples for PCR-RFLP were collected at 6 months of age and animals were monitored until either culling or 2,340 days from birth. Three SNP in SELPEx4-6 formed a haplotype block containing a Glu/Ala substitution at rs42312260. This region was associated with poor fertility and reduced survival times. SELPEx8 (rs378218397) coded for a Val475Met variant locus in the linking region between consensus repeats 4 and 5, which may influence glycosylation. The synonymous SNP rs110045112 in SELEEx14 deviated from Hardy Weinberg equilibrium. For both this SNP and rs378218397 there were too few AA homozygotes present in the population and AG heterozygotes had significantly worse fertility than GG homozygotes. Small changes in milk production associated with some SNP could not account for the reduced fertility and only SELPEx6 showed any association with somatic cell count. These results suggest that polymorphisms in SELP and SELE are associated with the likelihood of successful pregnancy, potentially through compromised implantation and placental development