The role of prolactin and growth hormone in mammary gland development

Development and differentiation of the mammary gland occur primarily during pregnancy. Females homozygous (-/-) for the null mutation of the PRL receptor (PRLR) gene are sterile due to a complete failure of blastocysts to implant. In progesterone-treated mice pregnancy is rescued but the mammary gland is severely underdeveloped. Interestingly, females hemizygous for the PRLR (+/-) in their first lactation show an almost complete failure to lactate. This phenotype disappears in the second and subsequent pregnancies in inbred 129/Sv mice but is maintained in inbred C57BL/6 mice. In GH receptor (GHR) KO mice litter size is markedly decreased, probably due to an ovarian defect. To assess the relevance of the GH and PRLRs in the mammary gland development, GHR and PRLR null epithelia were transplanted into cleared fat pads of wild-type mice. Such studies show that epithelial GHR is not required for functional mammary development. In contrast, epithelial PRLRs are required for mammary development and milk protein gene expression during pregnancy. Since ductal development is impaired in GHR -/- mice, it appears that GH signals through the stromal compartment. In summary, it is now established that GH and PRL activate Stat5 in separate compartments, reflecting their specific roles in ductal and alveolar development and differentiation.     

Initial graft size and not the innate immune response limit survival of engrafted neural stem cells

Transplantation of neural stem cells (NSCs) appears to be a promising regenerative therapy for a variety of neurological disorders. Nevertheless, NSC engraftment is limited by the number of surviving cells. To maximize stem cell‐mediated effects, timing of implantation and cell number have to be precisely evaluated. Here, a transgenic murine NSC line was optimized for high expression levels of the imaging reporters Luc2 and copGFP. NSCs of 150 000, 75 000, 15 000 or 1500 cells or Hanks buffered salt solution were implanted into the striatum of nude mice. The survival of NSCs was monitored with in vivo bioluminescence imaging (BLI) over 2 weeks and brain sections were histologically analysed for glial cells of the innate immune system. The longitudinal in vivo BLI data revealed a significantly reduced viability with the highest rate for 150 000 engrafted NSCs. The cell loss was not correlated with the number of Iba‐1⁺ immune cells nor GFAP⁺ astrocytes. Histological quantification of copGFP⁺ cells at 14 days postimplantation confirmed the in vivo data with the highest density of copGFP⁺ cells in the 150 000‐cell graft and the highest survival rate for 1500 cells/graft. In conclusion, regenerative therapies should strictly evaluate the maximal number of stem cells to be transplanted in one location, as the results suggest that there is a critical limit of cells able to survive in the adult brain. Survival is limited by availability of oxygen and nutrients but not the inflammatory response induced by the implantation.     

Acupuncture for Chronic Pain: Update of an Individual Patient Data Meta-Analysis

Despite wide use in clinical practice, acupuncture remains a controversial treatment for chronic pain. Our objective was to update an individual patient data meta-analysis to determine the effect size of acupuncture for 4 chronic pain conditions. We searched MEDLINE and the Cochrane Central Registry of Controlled Trials randomized trials published up until December 31, 2015. We included randomized trials of acupuncture needling versus either sham acupuncture or no acupuncture control for nonspecific musculoskeletal pain, osteoarthritis, chronic headache, or shoulder pain. Trials were only included if allocation concealment was unambiguously determined to be adequate. Raw data were obtained from study authors and entered into an individual patient data meta-analysis. The main outcome measures were pain and function. An additional 13 trials were identified, with data received for a total of 20,827 patients from 39 trials. Acupuncture was superior to sham as well as no acupuncture control for each pain condition (all P?<?.001) with differences between groups close to .5 SDs compared with no acupuncture control and close to .2 SDs compared with sham. We also found clear evidence that the effects of acupuncture persist over time with only a small decrease, approximately 15%, in treatment effect at 1 year. In secondary analyses, we found no obvious association between trial outcome and characteristics of acupuncture treatment, but effect sizes of acupuncture were associated with the type of control group, with smaller effects sizes for sham controlled trials that used a penetrating needle for sham, and for trials that had high intensity of intervention in the control arm. We conclude that acupuncture is effective for the treatment of chronic pain, with treatment effects persisting over time. Although factors in addition to the specific effects of needling at correct acupuncture point locations are important contributors to the treatment effect, decreases in pain after acupuncture cannot be explained solely in terms of placebo effects. Variations in the effect size of acupuncture in different trials are driven predominantly by differences in treatments received by the control group rather than by differences in the characteristics of acupuncture treatment.

Impact of Physical Activities on Frailty in Community-Dwelling Older Women

Aims: The aim of the study was to determine whether increased physical activities (PA) affect frailty for old women, 75 years and older (OO), compared to 60–74 years old (YO). Methods: This cross-sectional study measured 19 frailty indicators (muscle strength and endurance, balance, gait characteristics, and function), using 46 community-dwelling women. PA were divided into three levels by caloric expenditure per week (<2,000 kcal/week, 2,000–3,999 kcal/week, >4,000 kcal/week). Results: As PA level increased, a gap (=difference) between OO and YO narrowed for step length and function, but for quadriceps strength and endurance, a gap widened. Conclusions: Frailty progresses with aging but older women who engage in a high level of physical activity (>4,000 kcal/week) can increase mobility and functional capacity, but not for muscle strength and endurance. Starting regular resistance training activities early in the aging process is critical to improve or maintain muscle quality to offset age-related frailty.     

A US Population Health Survey on the Impact of COVID-19 Using the EQ-5D-5L

BackgroundThe COVID-19 pandemic has resulted in negative impacts on the economy, population health, and health-related quality-of-life (HRQoL).ObjectiveTo assess the impact of COVID-19 on US population HRQoL using the EQ-5D-5L.DesignWe surveyed respondents on physical and mental health, demographics, socioeconomics, brief medical history, current COVID-19 status, sleep, dietary, financial, and spending changes. Results were compared to online and face-to-face US population norms. Predictors of EQ-5D-5L utility were analyzed using both standard and post-lasso OLS regressions. Robustness of regression coefficients against unmeasured confounding was analyzed using the E-Value sensitivity analysis.SubjectsAmazon MTurk workers (n=2776) in the USA.Main MeasuresEQ-5D-5L utility and VAS scores by age group.Key ResultsWe received n=2746 responses. Subjects 18–24 years reported lower mean (SD) health utility (0.752 (0.281)) compared with both online (0.844 (0.184), p=0.001) and face-to-face norms (0.919 (0.127), p<0.001). Among ages 25–34, utility was worse compared to face-to-face norms only (0.825 (0.235) vs. 0.911 (0.111), p<0.001). For ages 35–64, utility was better during pandemic compared to online norms (0.845 (0.195) vs. 0.794 (0.247), p<0.001). At age 65+, utility values (0.827 (0.213)) were similar across all samples. VAS scores were worse for all age groups (p<0.005) except ages 45–54. Increasing age and income were correlated with increased utility, while being Asian, American Indian or Alaska Native, Hispanic, married, living alone, having history of chronic illness or self-reported depression, experiencing COVID-19-like symptoms, having a family member diagnosed with COVID-19, fear of COVID-19, being underweight, and living in California were associated with worse utility scores. Results were robust to unmeasured confounding.ConclusionsHRQoL decreased during the pandemic compared to US population norms, especially for ages 18–24. The mental health impact of COVID-19 is significant and falls primarily on younger adults whose health outcomes may have been overlooked based on policy initiatives to date.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-06674-z.