Phase 3 Study Assessing Lot-to-lot Consistency of RSVPreF3 Vaccine and its Immune Response, Safety, and Reactogenicity When Co-administered with FLU-D-QIV.

BACKGROUND: A single-dose investigational respiratory syncytial virus (RSV) vaccine, RSV prefusion protein F3 (RSVPreF3), was co-administered with a single-dose quadrivalent influenza vaccine (FLU-D-QIV) in a phase 3, randomized, controlled, multicenter study in healthy, non-pregnant women aged 18-49 years. METHODS: The study was observer-blind to evaluate the lot-to-lot consistency of RSVPreF3, and single-blind to evaluate the immune response, safety, and reactogenicity of RSVPreF3 co-administered with FLU-D-QIV. RESULTS: A total of 1415 participants were included in the per-protocol set. There was a robust immune response at day 31 across each of the 3 RSVPreF3 vaccine lots; adjusted geometric mean concentration ratios (95% confidence interval [CI]) were 1.01 (0.91, 1.12), 0.93 (0.84, 1.03), and 0.92 (0.83, 1.02) for RSV1/RSV2, RSV1/RSV3, and RSV2/RSV3, respectively. For FLU-D-QIV co-administered with RSVPreF3, versus FLU-D-QIV alone at day 31, noninferiority was satisfied for 3 of 4 strains assessed, with the lower limit of the 95% CI for geometric mean ratio >0.67. CONCLUSIONS: Immunogenic consistency was demonstrated for 3 separate lots of RSVPreF3. Immunogenic noninferiority was demonstrated when comparing FLU-D-QIV administered alone, versus co-administered with RSVPreF3, for 3 strains of FLU-D-QIV. Co-administration was well tolerated, and both vaccines had clinically acceptable safety and reactogenicity profiles. CLINICAL TRIALS REGISTRATION: NCT05045144; EudraCT, 2021-000357-26.

This was a phase 3 study that compared antibodies against respiratory syncytial virus (or RSV for short) between women who were given 3 different production batches of RSV prefusion protein F3 (known as RSVPreF3) vaccine. The study also compared the antibodies between women who received either an RSV vaccine together with a flu vaccine (known as FLU-D-QIV), or a flu vaccine alone. The flu vaccine contained 4 different strains of flu virus. The study involved 1415 healthy, non-pregnant women aged 18­49 years. The antibodies checked after 31 days showed strong immune responses for all 3 RSV vaccine production batches, and similar immune responses between each of the 3 RSV vaccine production batches. The immune response of 3 of the 4 flu strains was not less when the flu vaccine was given together with the RSV vaccine than the immune response when flu vaccine was given alone and both vaccines were well tolerated.

Pelvic floor muscle strength and influencing factors based on vaginal manometry among healthy women at different life stages: A multicentre cross-sectional study.

OBJECTIVE: To assess pelvic floor muscle (PFM) strength and influencing factors among healthy women at different life stages. DESIGN: Multicentre cross-sectional study. SETTING: Fourteen hospitals in China. POPULATION: A total of 5040 healthy women allocated to the following groups (with 1680 women per group): premenopausal nulliparous, premenopausal parous and postmenopausal. METHODS: The PFM strength was evaluated by vaginal manometry. Multivariate logistic regression was used to determine the influencing factors for low PFM strength. MAIN OUTCOME MEASURES: Maximum voluntary contraction pressure (MVCP). RESULTS: The median MVCP values were 36, 35 and 35 cmH2O in premenopausal nulliparous (aged 19-51 years), premenopausal parous (aged 22-61 years), and postmenopausal (aged 40-86 years) women, respectively. In the premenopausal nulliparous group, physical work (odds ratio, OR 2.05) was the risk factor for low PFM strength, which may be related to the chronic increased abdominal pressure caused by physical work. In the premenopausal parous group, the number of vaginal deliveries (OR 1.28) and diabetes (OR 2.70) were risk factors for low PFM strength, whereas sexual intercourse (<2 times per week vs. none, OR 0.55; ≥2 times per week vs. none, OR 0.56) and PFM exercise (OR 0.50) may have protective effects. In the postmenopausal group, the number of vaginal deliveries (OR 1.32) and family history of pelvic organ prolapse (POP) (OR 1.83) were risk factors for low PFM strength. CONCLUSIONS: Physical work, vaginal delivery, diabetes and a family history of POP are all risk factors for low PFM strength, whereas PFM exercises and sexual life can have a protective effect. The importance of these factors varies at different stages of a woman's life.

A short-term intervention of ingesting iron along with methionine and threonine leads to a higher hemoglobin level than that with iron alone in young healthy women: a randomized, double-blind, parallel-group, comparative study.

PURPOSE: Enhancing iron absorption and utilization is important for amelioration iron status faster and thereby, for improving quality of life. Dietary protein and amino acids, including methionine and threonine, have been reported to facilitate the absorption and utilization of dietary iron. Here, we investigated the effect of combined ingestion of methionine, threonine, and iron on the improvement of iron status during a short-term intervention, by comparing that with iron ingestion alone in healthy young women. METHODS: This was a randomized, double-blind, parallel-group, comparative study with 45 participants (aged 20-39) randomly assigned to three groups (n = 15 each): one group was administered 200 mg methionine, 400 mg threonine, and 6 mg iron once daily (FEMT); another ingested 6 mg iron alone (FE); and the third group ingested a placebo (PCG). Blood samples and dietary nutrient data were collected before the intervention (week 0) and after 2, 4, and 6 weeks. Serum iron, hemoglobin, transferrin, and ferritin levels were measured. RESULTS: Blood hemoglobin levels were significantly higher in the FEMT than in the FE group (P < 0.05) at week 4. Serum iron, transferrin, and ferritin levels were not changed across groups. In addition, our analyses showed that the observed increase in hemoglobin levels was affected by the intervention rather than changes in dietary nutrient intake. CONCLUSIONS: Ingestion of methionine and threonine with low doses of iron leads to a higher hemoglobin levels than that with iron alone in a short period of 4 weeks. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trial Registry (UMIN000046621).

Intra- and inter-cycle variability of anti-Müllerian hormone (AMH) levels in healthy women during non-consecutive menstrual cycles: the BICYCLE study.

OBJECTIVES: Determine variability of serum anti-Müllerian hormone (AMH) levels during ovulatory menstrual cycles between different women (inter-participant), between non-consecutive cycles (inter-cycle) and within a single cycle (intra-cycle) in healthy women. METHODS: Eligible participants were women aged 18-40 years with regular ovulatory menstrual cycles. Serum samples were collected every second day during two non-consecutive menstrual cycles. AMH levels were measured in triplicate using the Elecsys® AMH Plus immunoassay (Roche Diagnostics). AMH level variability was evaluated using mixed-effects periodic regression models based on Fourier series. The mesor was calculated to evaluate inter-participant and inter-cycle variability. Inter- and intra-cycle variability was evaluated using peak-to-peak amplitudes. Separation of biological and analytical coefficients of variation (CVs) was determined by analysing two remeasured AMH levels (with and without original AMH levels). RESULTS: A total of 47 women were included in the analysis (42 assessed over two cycles; five one cycle only). CV of unexplained biological variability was 9.61%; analytical variability was 3.46%. Inter-participant variability, given by time-series plots of AMH levels, was greater than inter-cycle variability. Between individual participants, both mesor and peak-to-peak amplitudes proved variable. In addition, for each participant, intra-cycle variability was higher than inter-cycle variability. CONCLUSIONS: Inter-participant and intra-cycle variability of AMH levels were greater than inter-cycle variability. Unexplained biological variability was higher than analytical variability using the Elecsys AMH Plus immunoassay. Understanding variability in AMH levels may aid in understanding differences in availability of antral ovarian follicles during the menstrual cycle, which may be beneficial in designing gonadotropin dosage for assisted reproductive technology.

Vaginal Tampon Colonization by Staphylococcus aureus in Healthy Women.

Tampons recovered from a cohort of 737 healthy women (median age, 32 years) were analyzed for the presence of Staphylococcus aureus A total of 198 tampons (27%) were colonized by S. aureus, 28 (4%) by a strain producing toxic shock syndrome toxin 1 (TSST-1). S. aureus was detected more frequently in tampons that did not require an applicator for their insertion (74/233 [32%] versus 90/381 [24%]; odds ratio [OR] = 1.51 [95% confidence interval, 1.04 to 2.17]) and in women who used an intrauterine device for contraception (53/155 [34%] versus 145/572 [27%]; OR = 1.53 [95% confidence interval, 1.05 to 2.24]). The S. aureus strains isolated from tampons belonged to 22 different clonal complexes (CCs). The most prevalent CC was CC398 agr1 (n = 57 [27%]), a clone that does not produce superantigenic toxins, followed by CC30 agr3 (n = 27, 13%), producing TSST-1 (24/27 [89%]), the principal clone of S. aureus involved in menstrual toxic shock syndrome (MTSS).IMPORTANCE Menstrual toxic shock syndrome (MTSS) is an uncommon severe acute disease that occurs in healthy menstruating women colonized by TSST-1-producing S. aureus who use intravaginal protection, such as tampons and menstrual cups. The catamenial product collected by the protection serves as a growth medium for S. aureus and allows TSST-1 production. Previous studies evaluated the prevalence of genital colonization by S. aureus by vaginal swabbing, but they did not examine tampon colonization. This study demonstrated a high prevalence of tampon colonization by S. aureus and the presence of the CC30 TSST-1 S. aureus clone responsible for MTSS in tampons from healthy women. The results support the vaginal carriage of this lineage in healthy women. In addition, the higher prevalence of S. aureus within tampons that do not require an applicator indicates a crucial role for handwashing before tampon handling to decrease the risk of tampon contamination.

Smoke exposure from chronic biomass burning induces distinct accumulative systemic inflammatory cytokine alterations compared to tobacco smoking in healthy women.

Long-term exposure to biomass-burning smoke (BS) is associated with chronic obstructive pulmonary disease (COPD), asthma, and other chronic inflammatory lung diseases. BS results from such processes as the burning of wood for indoor cooking and heating, with women and children having the highest exposure rate. This study aimed to analyze the accumulative alterations in cytokine levels associated with BS (from wood) compared to tobacco smoke (TS) in healthy adult women. The levels of 27 cytokines were analyzed in the serum of 100 women, including 40 tobacco smokers/non-exposed to BS (TS+/BS-), 30 never-smokers/exposed to BS (TS-/BS+) and 30 never-smokers/non-exposed to BS (TS-/BS-) as controls, using 27-Plex immunoassay. The chronic BS exposure index was rated at ≥100 h-years, and the tobacco-smoking index was ≥10 pack-years. Compared to TS-/BS-, TS+/BS- had higher levels of IL-2, IL-9, MCP-1, MIP-1ß, and VEGF, while TS-/BS+ showed higher levels of IL-1ra, IL-6, IL-8, Eotaxin, IP-10, RANTES, and VEGF, presenting a distinct inflammatory profile that may favor an eosinophil-derived inflammatory response to BS exposure. Compared to TS+/BS-, TS-/BS+ expressed higher levels of IP-10 and IL-8, but lower levels of IL-2 and MIP-1ß. Gene-disease database analysis showed that altered cytokines in both TS+/BS- and TS-/BS+ are associated with asthma, COPD, lung fibrosis, and lung cancer. In conclusion, chronic BS exposure induces distinct systemic inflammatory cytokine alterations compared to tobacco smokers in healthy women. These findings provide new insights into how long-term exposure to BS affects the inflammatory response-and potentially the health-of adult women.

Evaluating the Health Outcomes of the Healthy Women Healthy Babies Program in Delaware.

OBJECTIVES: The Delaware Healthy Women Healthy Babies Program (HWHB) was developed in response to increasing rates of infant mortality (IMR) and widening racial disparity. The primary aim of this study was to examine birth outcomes of enrolled and non-enrolled black and Hispanic women in the program whose payer was Medicaid. METHODS: We utilized a retrospective cohort of linked birth certificate and HWHB program participant data during 2011-2015. Our primary outcome variables (dependent variables) of interest included cigarette use, low birth weight, preterm birth and neonatal mortality. We utilized inverse probability of treatment weighting (IPTW) and estimated crude odds ratios (COR) and adjusted odds ratio (AOR) with 95% confidence intervals (CI) using IPTW as a weight variable. RESULTS: HWHB enrolled women were 10% less likely to smoke during pregnancy COR 0.89 (95% CI 0.82-0.96); were 9% less likely to deliver a low birth weight infant (AOR 0.91; 95% CI 0.84-0.99; p = 0.023); were 15% less likely to deliver a preterm infant (AOR 0.85; 0.78-0.92; p < .0001) as compared with non-HWHB women. Infants delivered by HWHB enrolled women had 27% less likelihood (AOR 0.73; 95% CI 0.54-0.98; p = 0.035) of experiencing a neonatal death (i.e., < 28 days) as compared with infants of non-enrolled HWHB women. CONCLUSION: The primary goal of this evaluation was to assess the effectiveness of the HWHB program on modifiable risk factors of IMR among HWHB enrolled and non-enrolled women. We found that HWHB program is a promising practice in improving the outcomes of infants born to participating black and Hispanic mothers.

Breast cancer-linked lncRNA u-Eleanor is upregulated in breast of healthy women with lack or short duration of breastfeeding.

Recently, it has been revealed that estrogen-related reproductive factors are linked with some early gene expression lesions associated with malignancy in clinically healthy breasts. Accordingly, the aim of the current study was to evaluate the association of expression levels of estrogen-related long noncoding RNAs (lncRNAs) upstream Eleanor (u-Eleanor) and HOX antisense intergenic RNA (HOTAIR) with the different patterns of reproductive factors in breast tissue of healthy women. The subjects of this study were 98 cancer-free women who had undergone cosmetic mammoplasty. The expression levels of u-Eleanor and HOTAIR were measured using quantitative real-time polymerase chain reaction. The results of the current study showed that the women without a history of breastfeeding had a high-level expression of u-Eleanor compared with the women with a breastfeeding duration greater than 6 to 24 months (P = 0.03) as well as the women with a breastfeeding duration of more than 24 months (P = 0.005). Furthermore, a higher expression of u-Eleanor was found in the women with a short breastfeeding duration for 1 to 6 months than that in the women with a breastfeeding duration of greater than 24 months (P = 0.02). In the same way, the results of correlation test (r = -0.258; P = 0.036) and multivariate regression model (ß = -0.321; P = 0.023) are indicative of a significant relationship of elevated expression of u-Eleanor with decreasing breastfeeding duration in the women. These findings could be important to identify the molecular mechanisms behind the relationship between a lack or short duration of the breastfeeding and the risk of breast cancer, which has previously been reported by epidemiological studies.

Comparison of static and dynamic balance during early follicular and ovulation phases in healthy women, using simple, clinical tests: a cross sectional study.

Balance may be influenced by several factors. The menstrual cycle can be considered as an important factor which may affect postural control. This study was aimed to investigate the influence of early follicular and ovulation phases on static and dynamic balance indices. Thirty non-athlete healthy women with a regular menstrual cycle aged between 18 and 25 years participated in the study. Static balance was evaluated through single-leg stance test and dynamic balance was investigated with posteromedial direction of Y- balance test during early follicular and ovulation (24-48 hours after the peak of estrogen) phases of menstrual cycle. The balance tests were performed in a randomized order in each session. A paired t-test analysis was performed to compare the data during the early follicular and ovulation phases. The results indicated that both static and dynamic balance scores were higher in ovulation phase in comparison to early follicular phase (p < .001). It is worth noting to consider the balance fluctuations during different phases of menstrual cycle when prescribing exercise programs for healthy women or when they participate in sport or recreational activities.

Effect of administration of a probiotic preparation on gut microbiota and immune response in healthy women in India: an open-label, single-arm pilot study.

BACKGROUND: Probiotics have been shown to be useful for the treatment of many disease conditions. These beneficial effects are believed to be mediated by change in the composition of gut microbiota and modulation of the host immune responses. However, the available data on the effect of probiotics on these parameters are quite limited. METHODS: We studied the composition of fecal microbiota, using 16S rRNA sequencing, and host immune responses in peripheral blood (plasma cytokine levels, T cell subsets and in vitro cytokine production after stimulation with anti-CD3/CD28 antibody or lipopolysaccharide) in a group of 14 healthy women at three time-points - before and after administration of a probiotic preparation (a capsule of VSL#3, each containing 112.5 billion freeze-dried bacterial cells belonging to 8 species, twice a day for 4 weeks), and 4-weeks after discontinuation of the probiotic administration. RESULTS: There was no change in the abundance of various bacterial taxa as well as in the alpha diversity of gut microbiota following administration of the probiotic, or following its discontinuation. Probiotic administration led to a reduction in the relative frequency of circulating Th17 cells, and in vitro production of cytokines in whole-blood cultures in response to lipopolysaccharide stimulation. However, it had no effect on the relative frequencies of Th1, Th2 and T regulatory cells among circulating peripheral blood mononuclear cells, on plasma cytokine levels and on in vitro production of cytokines by T cells. CONCLUSIONS: We found that VSL#3 administration did not lead to any changes in gut flora, but led to a reduction in the frequency of Th17 cells and in the production of pro-inflammatory cytokine on lipopolysaccharide stimulation. These findings suggest that the beneficial anti-inflammatory effect of this preparation in patients with autoimmune and allergic disorders may be related to reduced production of monocyte-derived cytokines rather than to changes in the composition of gut microbiota. TRIAL REGISTRATION: NCT03330678 , Date of registration 30th October 2017. Retrospectively registered.

Vaginal microbiome.

OBJECTIVE: Presentation of complex information about the vaginal microbiota from historical view to current concepts with focus on latest findings on the structure and functioning of the vaginal microbiome. DESIGN: Review article. SETTING: Department of Clinical Microbiology, University Hospital and Faculty of Medicine in Hradci Králové, Charles University in Prague. METHODS: Literature review using the databases (PubMed, Web of Science, Ovid, etc.) with keywords (vaginal microbiota/ microbiom; vaginal discharge; bacterial vaginosis; vulvovaginitis; vaginal Lactobacillus). RESULTS: The vaginal microbiome is a specific compartment of the human microbiome. Unique conditions of the vagina are characterized by a few microbial species, usually lactobacilli, which are able to utilize glycogen, which is under control of estrogens. Lactobacilli and other fermentative bacteria together with vaginal epithelial cells produce lactic acid and are responsible for acidifying vaginal milieu. Lactic acid occurs in two isomeric forms, and their relative ratio is likely to give the vaginal microbiota a certain degree of stability and ability to withstand some infections. This microbiota is manifested by a low degree of diversity and by the high dynamics of changes of its composition under the influence of various exogenous and endogenous factors. Increase in diversity can be paradoxically associated with a dysbiosis such as bacterial vaginosis. Individual species of lactobacilli mainly Lactobacillus crispatus characterize the main community state types in the vagina. Apart from lactobacilli, healthy women may be colonized with a non-lactobacillary microbiota whose rate is dependent on ethnicity. CONCLUSION: The definition of vaginal microbiota cannot be only related to the presence or absence of individual microorganisms, although the incidence of some of them can be correlated with dysbiosis or eubiosis. The composition of microbiota is important, but it is only one of the basic attributes of normal vaginal microbiota, but not sufficient; that is the functional definition of vaginal microbiota in relation to its structure and dynamics, including the influence of ethnicity, physiological status of the vagina, and genetic disposition of woman.

Uroflowmetry in healthy women: A systematic review.

BACKGROUND: Although uroflowmetry is a widely used diagnostic test, reference values of uroflowmetry parameters in women are lacking making it difficult to interpret the test results. AIM: To quantify the range of results in uroflowmetry parameters in healthy women based on a systematic review. METHODS: A search was made in the International Continence Society standardization articles, PubMed, Embase and the Cochrane Library (from inception to 27 February 2014). Studies on uroflowmetry in healthy women were included. The selected articles were examined using a critical appraisal process based on the QUADAS-2 tool and the Critical Appraisal Skills Program. RESULTS: Mean values of uroflowmetry parameters in healthy women (mean age 37.1 years) were: voided volume (VV) 338 ml (SD 161), maximum flow rate (Qmax) 23.5 ml/s (SD 10), average flow rate (Qave) 13 ml/s (SD 6), postvoid residual (PVR) 15.5 ml (SD 25), voiding time (VT) 29 sec (SD 17), and time to maximum flow rate (time to Qmax) 8 sec (SD 6). Qmax was dependent on VV. There was no clear relationship between Qmax and age, and no correlation between parity and Qmax. A normal shape of the uroflowmetry curve was seen in 70-80% of the flows. CONCLUSION: This systematic review provides an overview of the range of results of uroflowmetry parameters in healthy women. Neurourol. Urodynam. 36:953-959, 2017. © 2016 Wiley Periodicals, Inc.

Seroprevalence of HTLV-1 and HTLV-2 amongst mothers and children in Malawi within the context of a systematic review and meta-analysis of HTLV seroprevalence in Africa.

OBJECTIVES: Human T-lymphotropic virus (HTLV)-1 causes T-cell leukaemia and myelopathy. Together with HTLV-2, it is endemic in some African nations. Seroprevalence data from Malawi are scarce, with no reports on associated disease incidence. HTLV seroprevalence and type were tested in 418 healthy mothers from Malawi. In addition, we tested the sera of 534 children to investigate mother-to-child transmission. To provide context, we conducted a systematic review and meta-analysis of HTLV seroprevalence in African women and children. METHODS: Stored samples from a previous childhood cancer and BBV study were analysed. ELISA was used for HTLV screening followed by immunoblot for confirmation and typing. Standard methods were used for the systematic review. RESULTS: HTLV seroprevalence was 2.6% (11/418) in mothers and 2.2% (12/534) in children. Three mothers carried HTLV-1 alone, seven had HTLV-2 and one was dually infected. Three children carried HTLV-1 alone, seven had HTLV-2 and two were dually infected. Only two corresponding mothers of the 12 HTLV-positive children were HTLV positive. The systematic review included 66 studies of women and 13 of children conducted in 25 African countries. Seroprevalence of HTLV-1 varied from 0 to 17% and of HTLV-2 from 0 to 4%. CONCLUSIONS: In contrast to findings from other studies in Africa, the seroprevalence of HTLV-2 was higher than that of HTLV-1 in Malawi and one of the highest for the African region. The lack of mother-child concordance suggests alternative sources of infection among children. Our data and analyses contribute to HTLV prevalence mapping in Africa.

Temporal and spatial differences in the vaginal microbiome of Chinese healthy women.

Background: Up the reproductive tract, there are large differences in the composition of vaginal microbes. Throughout the menstrual cycle, the structure of the vaginal microbiome shifts. Few studies have examined both in combination. Our study was designed to explore trends in the microbiome of different parts of the vagina in healthy women over the menstrual cycle. Methods: We performed metagenomic sequencing to characterize the microbiome differences between the cervical orifice and mid-vagina throughout the menstrual cycle. Results: Our results showed the vaginal microbiome of healthy women in the cervical orifice and the mid-vagina was similar during the periovulatory and luteal phases, with Lactobacillus being the dominant bacteria. In the follicular phase, Acinetobacter was detected in the cervical orifice. From the follicular phase to the luteal phase, the community state types (all five community status types were defined as CSTs) in samples No. 10 and No. 11 changed from CST III to CST I. In addition, the composition of the vaginal microbiome in healthy women from different regions of China was significantly different. We also detected viruses including Human alphaherpesvirus 1 (HSV-1) during periovulatory phase. Conclusion: This study is valuable for understanding whether the microbial composition of the vagina is consistent in different parts of the menstrual cycle.

Variation in normative values of major clinical biochemistry analytes in healthy reproductive-age women in India: A subset of data from a National Indian Council of Medical Research-Polycystic Ovary Syndrome task force study.

OBJECTIVES: Clinical biochemistry reference intervals (RIs) play a crucial role in interpreting patient test results and making informed clinical decisions. Using data from an ongoing Indian Council of Medical Research-National task force study on healthy women, normative ranges for commonly analyzed biochemical analytes were established. MATERIALS AND METHODS: A.total of 13,181 women of reproductive age (18-40 years) were recruited from different urban and rural regions of the country, of which 9898 women signed an informed consent were included. Among these, women having features of hyperandrogenism, menstrual cycle irregularities, and comorbidities were excluded. RIs of 22 analytes were computed in the remaining 938 women controls. To estimate the 95% range of the reference distribution, the limits of the 2.5th percentile and the 97.5th percentile were used in the study. RESULTS: Mean ± standard deviation of age and body mass index of participants was 30.12 ± 6.32 years and 22.8 ± 3.36 kg/m2 respectively. Centiles (2.5th-97.5th) of liver function parameters, lipid parameters, glycaemic parameters, and renal parameters are presented. No significant difference in analytes was observed in relation to the area of residence, and age groups except in albumin (P = 0.03). The distribution of most of the parameters was consistent with the various RI studies conducted in India as well as other countries. CONCLUSION: This is the first study generating biochemical RIs data among a large representative sample of healthy reproductive-age women recruited using a robust design across the country. The resource may serve as a reference range for common biochemical analytes for future in this age group.

Effect of Whole-Body Vibration Training on Hemorheological Blood Indices in Young, Healthy Women.

The aim of the study is to assess the effect of single and 12-week WBVT and training without vibration on changes in hemorheological blood indices and plasma fibrinogen levels in young, healthy women. Three groups are distinguished: the experimental group-participating in WBVT (n = 17); the comparison group-implementing the same physical exercise protocol without the vibration factor (n = 12); and the control group-no intervention (n = 17). In the experimental and comparison group, blood is collected before and after the first and last training, while in the control group, blood is collected twice, 3 months apart. After a series of WBVT, a significant decrease in the mean erythrocyte volume and mean hemoglobin mass in erythrocytes, as well as a slight increase in the mean erythrocyte hemoglobin concentration, is found, and the effect of the last training is a significant decrease in plasma volume. Under the influence of repeated WBVT, there is an increase in erythrocyte deformability at low shear stress and an increase in the aggregation amplitude. The study shows that WBVT improves blood flow in the vessels and does not affect erythrocyte aggregation and the level of fibrinogen, which confirms the safety of this form of exercise.

Pregnancy-associated systemic gene expression compared to a pre-pregnancy baseline, among healthy women with term pregnancies.

Background: Pregnancy is known to induce extensive biological changes in the healthy mother. Little is known, however, about what these changes are at the molecular level. We have examined systemic expression changes in protein-coding genes and long non-coding (lnc) RNAs during and after pregnancy, compared to before pregnancy, among healthy women with term pregnancies. Methods: Blood samples were collected from 14 healthy women enrolled in our prospective pregnancy cohort at 7 time-points (before, during and after pregnancy). Total RNA from frozen whole blood was used for RNA sequencing. Following raw read alignment and assembly, gene-level counts were obtained for protein-coding genes and long non-coding RNAs. At each time-point, cell type proportions were estimated using deconvolution. To examine associations between pregnancy status and gene expression over time, Generalized Estimating Equation (GEE) models were fitted, adjusting for age at conception, and with and without adjusting for changes in cell type proportions. Fold-changes in expression at each trimester were examined relative to the pre-pregnancy baseline. Results: Numerous immune-related genes demonstrated pregnancy-associated expression, in a time-dependent manner. The genes that demonstrated the largest changes in expression included several that were neutrophil-related (over-expressed) and numerous immunoglobulin genes (under-expressed). Estimated cell proportions revealed a marked increase in neutrophils, and less so of activated CD4 memory T cells, during pregnancy, while most other cell type proportions decreased or remained unchanged. Adjusting for cell type proportions in our model revealed that although most of the expression changes were due to changes in cell type proportions in the bloodstream, transcriptional regulation was also involved, especially in down-regulating expression of type I interferon inducible genes. Conclusion: Compared to a pre-pregnancy baseline, there were extensive systemic changes in cell type proportions, gene expression and biological pathways associated with different stages of pregnancy and postpartum among healthy women. Some were due to changes in cell type proportions and some due to gene regulation. In addition to providing insight into term pregnancy among healthy women, these findings also provide a "normal" reference for abnormal pregnancies and for autoimmune diseases that improve or worsen during pregnancy, to assess deviations from normal.

Mid-Luteal Olfactory Abilities Reveal Healthy Women's Emotional and Cognitive Functions.

Ovarian hormones modulate women's physical and psychological states periodically. Although the olfactory function is increasingly recognized as a reflection of physical and mental health conditions in the clinic, the role of olfaction in emotional and cognitive functions for healthy individuals has yet to be elucidated, especially when taking the menstrual cycle into account. We carried out a comprehensive investigation to explore whether the menstrual cycle could modulate women's olfactory function and whether healthy women's emotional symptoms and behavioral impulsivity could be characterized by their olfactory abilities at a specific menstrual cycle stage. Twenty-nine healthy young women were evaluated repeatedly using a standard olfactory test battery during the late follicular and mid-luteal phases. Their emotional symptoms and behavioral impulsivity were separately quantified via psychometric scales and a stop-signal task. We observed enhanced olfactory discrimination performance during the mid-luteal phase than the late follicular phase. We also found that women's better olfactory discrimination and worse olfactory threshold in the mid-luteal phase predicted fewer individual emotional symptoms and lower behavioral impulsivity, respectively. These relationships were nonetheless absent in the late follicular phase. Our data extend previous clinical observations of the coexistence of olfactory deficits and neuropsychiatric disorders, providing new insights into the significance of olfaction and ovarian hormones for emotional and cognitive functions.

The impact of childhood maltreatment on women's reproductive health, with a focus on symptoms of polycystic ovary syndrome.

BACKGROUND: Childhood maltreatment leads to lifelong health risks, particularly in women. Although reproductive health has been linked to such maltreatment, limited literature exists on its association with polycystic ovary syndrome (PCOS). OBJECTIVES: In a sample of psychiatrically healthy women, we evaluated the impact of child maltreatment (subtypes of abuse and neglect) on women's reproductive health outcomes, specifically PCOS. PARTICIPANTS AND SETTING: The 237 psychiatrically healthy women, aged between 18 and 79 years, were control participants in a case-control study (SHARED ROOTS), conducted in Cape Town, South Africa, between May 2014 and June 2017. METHODS: Probable PCOS was based on a history of symptoms of ovulatory dysfunction and hyperandrogenism or a diagnosis of PCOS. We conducted hierarchical logistic regression models to assess which child maltreatment subtypes (emotional, physical and sexual abuse and emotional and physical neglect) were significantly associated with PCOS, controlling for sociodemographic and clinical factors. RESULTS: Probable PCOS was present in 29 (12.2 %) women. Emotional abuse (31.6 %) was the most frequent type of child maltreatment and was significantly associated with PCOS (OR = 5.11, CI 1.87; 13.98), including when other maltreatment types were accounted for (OR = 3.90, CI 1.27; 12.02). Physical abuse was associated with PCOS (OR = 4.21, CI 1.43; 12.38), but was not significant when other maltreatment types were factored in. CONCLUSIONS: Child maltreatment is independently associated with PCOS in women without psychiatric disorders. In the context of all maltreatment subtypes, emotional abuse remained associated with PCOS, suggesting its unique effect on this endocrinopathy.

Evaluation of 3D vertebral and pelvic position by surface topography in asymptomatic females: presentation of normative reference data.

BACKGROUND: Deviations from a conventional physiologic posture are often a cause of complaint. According to current literature, the upright physiological spine posture exhibits inclinations in the sagittal plane but not in the coronal and transverse planes, but individual vertebral body positions of asymptomatic adults have rarely been described using surface topography. Therefore, this work aims to form a normative reference dataset for the thoracic and lumbar vertebral bodies and for the pelvis in all three planes in asymptomatic women. METHODS: In a prospective, cross-sectional, monocentric study, 100 pain-free asymptomatic women, aged 20-64 years were enrolled. Habitual standing positions of the trunk were measured using surface topography. Data were analyzed in all three planes. Age sub-analysis was: 1) ages ≤ 40 years and 2) ages ≥ 41 years. Two-sample t-tests were used for age comparisons of the vertebral bodies, vertebra prominence (VP)-L4, and global parameters. One-sample t-tests were used to test deviations from symmetrical zero positions of VP-L4. RESULTS: Coronal plane: on average, the vertebral bodies were tilted to the right between the VP and T4 (maximum: T2 - 1.8° ± 3.2), while between T6 and T11 they were tilted to the left (maximum: T7 1.1° ± 1.9). T5 and L2 were in a neutral position, overall depicting a mean right-sided lateral flexion from T2 to T7 (apex at T5). Sagittal plane: the kyphotic apex resided at T8 with - 0.5° ± 3.6 and the lumbar lordotic apex at L3 with - 2.1° ± 7.4. Transverse plane: participants had a mean vertebral body rotation to the right ranging from T6 to L4 (maximum: T11 - 2.2° ± 3.5). Age-specific differences were seen in the sagittal plane and had little effect on overall posture. CONCLUSIONS: Asymptomatic female volunteers standing in a habitual posture displayed an average vertebral rotation and lateral flexion to the right in vertebral segments T2-T7. The physiological asymmetrical posture of women could be considered in spinal therapies. With regard to spinal surgery, it should be clarified whether an approximation to an absolutely symmetrical posture is desirable from a biomechanical point of view? This data set can also be used as a reference in clinical practice. TRIAL REGISTRATION: This study was registered with WHO (INT: DRKS00010834) and approved by the responsible ethics committee at the Rhineland-Palatinate Medical Association (837.194.16).