Validation of urinary reproductive hormone measurements using a novel smartphone connected reader.

Home use tests to monitor hormone trends during the menstrual cycle have been available over-the-counter for a long time. However, these tests often depend upon manual readouts and hence may lead to false analysis. Furthermore, a lot of these tests are also not quantitative. The aim of this study was to evaluate the accuracy of the quantitative home-based fertility monitor, Inito Fertility Monitor (IFM) and to use it to identify novel hormone trends in natural menstrual cycles. There were two aspects to our analysis: (i) Evaluating the efficacy of Inito Fertility Monitor in the measurement of urinary Estrone-3-glucuronide (E3G), Pregnanediol glucuronide (PdG) and Luteinizing hormone (LH), and (ii) A retrospective study of patients' hormone profiles using IFM. To evaluate the efficacy, the recovery percentage of the three hormones from IFM was evaluated using standard spiked solutions, the accuracy of measurement was calculated and the correlation between reproducible values from IFM and ELISA was established. During the validation of IFM, novel hormone trends were also observed. In order to reinforce the observations, a second group of 52 women was recruited. Assessment of the accuracy of IFM and evaluation of the volunteer urine samples was performed in a laboratory. Home assessment of hormone analysis was carried out using IFM. For the validation study, 100 women aged 21-45 years with cycle lengths ranging from 21 to 42 days were recruited. The participants had no previously diagnosed infertility conditions and their cycle lengths did not vary for more than 3 days from the expected cycle length. Daily first morning urine samples were collected from these 100 women. For the second group, 52 women were selected meeting the same criteria set for the validation study and IFM was provided to these women for testing at home. Coefficient of variation and recovery percentage of IFM with respect to laboratory based ELISA. Percentage occurrence of novel hormone trends and AUC analysis of a novel criteria identified for confirming ovulation. We observed that with all three hormones, IFM had an accurate recovery percentage. We found that the assay has an average CV of 5.05% in PdG measurement, 4.95% in E3G measurement and 5.57% in LH measurement. Furthermore, in predicting the concentration of E3G, PdG and LH in urine samples, we show that IFM has a high correlation with ELISA. In this study, we could also reproduce hormones trends across the menstrual cycle that have been observed by previous studies. We also identified a novel criterion for earlier confirmation of ovulation which could accurately distinguish ovulatory from anovulatory cycles with 100% specificity and had an area under the ROC curve of 0.98. In addition, we identified a new hormone trend which could be observed in 94.5% of the ovulatory cycles. The Inito Fertility Monitor is an effective tool for calculating the urinary concentrations of E3G, PdG and LH and can also be used to provide accurate fertility scores and confirm ovulation. We show that certain hormone trends associated with urinary E3G, PdG and LH could be accurately captured using IFM. In addition, we report a novel criterion for earlier confirmation of ovulation compared to existing criteria. Finally, we present a novel hormone pattern associated with most of the menstrual cycles by examining hormone profiles from the volunteers recruited for the clinical trial.Trial registration: The trial is registered at the current controlled trials ISRCTN registry #ISRCTN15534557.

A novel home-use culture mechanism for identifying microbial load in urine samples.

Diagnosing a urinary tract infection (UTI) is typically a clinical procedure involving multiple steps. The need to perform a test depends on the presence of relevant symptoms. Given the current pandemic situation, visiting a clinic may not be a preferable choice for many users. Many vulnerable groups of patients, namely, males with certain predispositions and pregnant women, may not present with symptoms of UTI and may go undiagnosed, which could give rise to a more complicated situation. So far, microbial cultures have been used as the gold standard for the diagnosis of an infection. However, performing microbial cultures currently requires trained professionals and laboratory grade equipment. Therefore, there is a need for a home-use culture kit that can serve this purpose. To our knowledge, no such kit exists. Here, we present a feasibility study of an affordable and easy-to-use home-based setup for quantifying bacterial load in a urine. We believe that such a system can be used by people at home to monitor recurrent UTI infections and also by physicians to remotely monitor and prescribe narrow-spectrum antibiotics for more effective treatment.

Predicting serum hormone concentration by estimation of urinary hormones through a home-use device.

STUDY QUESTION: Can a home-use device be used to predict serum hormone levels? SUMMARY ANSWER: A home-use device can predict urinary hormone values which are well-correlated to serum concentrations of respective hormones and hence can be used as a proxy for serum measurements. WHAT IS KNOWN ALREADY: Home-use devices that predict ovulation are calibrated against the actual day of ovulation. However, the correlation of any quantitative system to serum hormone concentrations has not been established. STUDY DESIGN SIZE DURATION: A total of 73 data points obtained from 20 participants across different phases of the menstrual cycle, i.e. bleeding days, follicular phase and luteal phase were used to establish the correlation between serum hormones and urinary metabolite values. Single data points from 20 random users were used to assess the correlation established. PARTICIPANTS/MATERIALS SETTING METHODS: Participants were women in the fertile age groups and only current users of the home-use device. Selection was done based on inclusion and exclusion criteria. Blood hormones were tested using chemiluminescent immunoassays and urinary measurements were taken on the home-use device at home. MAIN RESULTS AND THE ROLE OF CHANCE: Serum estradiol (E2), progesterone (P4) and LH were correlated with urinary estrone-3-glucuronide (E3G), pregnanediol glucuronide (PdG) and LH with an R 2 of 0.96, 0.95 and 0.98, respectively. Repredicted serum concentration obtained by using the correlation equation had a correlation of 0.92, 0.94 and 0.93 in unknown samples. LIMITATIONS REASONS FOR CAUTION: The study was designed to include women who have normal cycle lengths regularly; therefore, the values obtained were in the normal range. Certain infertility conditions may cause the values to be higher and correlation in such cases needs to be established. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study imply a new tool that can be used by fertility specialists as a proxy for blood tests whenever required. Extended study on this system can enable its use in assisted reproductive techniques as well. STUDY FUNDING/COMPETING INTERESTS: No funding was received for this study. S.P. and D.D. are employees of the research and development division of Samplytics Technologies Pvt. Ltd. which is a forwarder for Inito Inc., USA. A.R. and V.A.V. are co-founders of Inito Inc., USA. TRIAL REGISTRATION NUMBER: The trial was registered at the International Standard Randomised Controlled Trial Number (ISRCTN) registry (Identifier: ISRCTN15534557).

Activation of Latent Courtship Circuitry in the Brain of Drosophila Females Induces Male-like Behaviors.

Courtship in Drosophila melanogaster offers a powerful experimental paradigm for the study of innate sexually dimorphic behaviors [1, 2]. Fruit fly males exhibit an elaborate courtship display toward a potential mate [1, 2]. Females never actively court males, but their response to the male's display determines whether mating will actually occur. Sex-specific behaviors are hardwired into the nervous system via the actions of the sex determination genes doublesex (dsx) and fruitless (fru) [1]. Activation of male-specific dsx/fru(+) P1 neurons in the brain initiates the male's courtship display [3, 4], suggesting that neurons unique to males trigger this sex-specific behavior. In females, dsx(+) neurons play a pivotal role in sexual receptivity and post-mating behaviors [1, 2, 5-9]. Yet it is still unclear how dsx(+) neurons and dimorphisms in these circuits give rise to the different behaviors displayed by males and females. Here, we manipulated the function of dsx(+) neurons in the female brain to investigate higher-order neurons that drive female behaviors. Surprisingly, we found that activation of female dsx(+) neurons in the brain induces females to behave like males by promoting male-typical courtship behaviors. Activated females display courtship toward conspecific males or females, as well other Drosophila species. We uncovered specific dsx(+) neurons critical for driving male courtship and identified pheromones that trigger such behaviors in activated females. While male courtship behavior was thought to arise from male-specific central neurons, our study shows that the female brain is equipped with latent courtship circuitry capable of inducing this male-specific behavioral program.