Data-driven insights can transform women's reproductive health.

This perspective explores the transformative potential of data-driven insights to understand and address women's reproductive health conditions. Historically, clinical studies often excluded women, hindering comprehensive research into conditions such as adverse pregnancy outcomes and endometriosis. Recent advances in technology (e.g., next-generation sequencing techniques, electronic medical records (EMRs), computational power) provide unprecedented opportunities for research in women's reproductive health. Studies of molecular data, including large-scale meta-analyses, provide valuable insights into conditions like preterm birth and preeclampsia. Moreover, EMRs and other clinical data sources enable researchers to study populations of individuals, uncovering trends and associations in women's reproductive health conditions. Despite these advancements, challenges such as data completeness, accuracy, and representation persist. We emphasize the importance of holistic approaches, greater inclusion, and refining and expanding on how we leverage data and computational integrative approaches for discoveries so that we can benefit not only women's reproductive health but overall human health.

Stabilizing breathing pattern using local mechanical vibrations: comparison of deterministic and stochastic stimulations in rodent models of apnea of prematurity.

Mechanical stimulation has been shown to reduce apnea of prematurity (AOP), a major concern in preterm infants. Previous work suggested that the underlying mechanism is stochastic resonance, amplification of a subthreshold signal by stochastic stimulation. We hypothesized that the mechanism behind the reduction of apnea length may not be a solely stochastic phenomenon, and suggest that a purely deterministic, non-random mechanical stimulation could be equally as effective. Mice and rats were anesthetized, tracheostomized, and mechanically ventilated to halt spontaneous breathing. Two miniature motors controlled by a microcontroller were attached around the abdomen. Ventilation was paused, stimulations were applied, and the time to the rodent's first spontaneous breath (T) was measured. Six spectrally different signals were compared to one another and the no-stimulation control in mice. The most successful deterministic stimulation (D) at reducing apnea was then compared to a pseudo-random noise (PRN) signal of comparable amplitude and frequency. CO2%, CO2 stabilization time (Ts), O2 saturation (SpO2%), and T were also measured. D significantly reduced T compared to no stimulation for medium and high amplitudes. PRN also reduced T, without  a difference between D and PRN. Furthermore, both stimulations significantly reduced Ts with no significant differences between the respective stimulations. However, there was no effect of D or PRN on SpO2%. The lack of differences between D and PRN led to an additional series of experiment comparing the same D to a band-limited white noise (WN) signal in young rats. Both D and WN were shown to significantly reduce T, with D showing statistical superiority in reduction of apnea. We further speculate that both deterministic and stochastic mechanical stimulations induce some form of mechanotransduction which is responsible for their efficacy, and our findings suggest that mechanical stimulation may be effective in treating AOP. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13534-021-00203-x.

Hydrocortisone, Ascorbic Acid, and Thiamine (HAT) Therapy Decreases Oxidative Stress, Improves Cardiovascular Function, and Improves Survival in Murine Sepsis.

INTRODUCTION: A small clinical trial showed HAT therapy improved survival but no studies have been reported in animal models to examine potential mechanisms. METHODS: Sepsis was induced in female mice using the cecal ligation and puncture (CLP) model. Physiologic parameters including heart rate (HR), pulse distension (PD), and respiratory rate (RR) were measured noninvasively at baseline, 6 and 24 h post CLP. These measurements stratified mice into predicted to live (Live-P) or die (Die-P). Mice were randomized to receive HAT therapy or vehicle. Oxidative stress was measured in peritoneal exudative cells 24 h after CLP. RESULTS: HR, PD, and RR all declined within the first 6 h of sepsis and were significantly lower in the Die-P mice compared with Live-P. HR 6 h post-CLP best predicted mortality and continued to decline between 6 and 24 h post CLP. Oxidative stress in peritoneal cells harvested 24 h post CLP (determined by 8 isoprostaglandin F2α and protein carbonyl derivatives) was significantly higher in the Die-P mice. HAT therapy was initiated 7 h post-CLP after mortality prediction and stratification. HAT significantly reduced oxidative stress in the Die-P mice without altering these parameters in the Live-P mice. HAT treatment prevented the decline in HR, again only in the Die-P mice. Mice treated with HAT therapy had significantly better survival. CONCLUSIONS: Physiologic parameters accurately predicted mortality. Die-P mice had significant oxidative stress compared with Live-P. HAT therapy significantly decreased oxidative stress, increased HR, and improved survival in the Die-P mice. These data suggest that HAT exerts a beneficial effect through reducing oxidative stress and improving cardiovascular function.