Throughout most of the ovulatory cycle, estrogen negative feedback restrains the GnRH neuronal system. Just before ovulation, however, estrogen negative feedback is removed to permit stimulation of the preovulatory GnRH/LH surge (positive feedback) by the circadian clock in the suprachiasmatic nucleus (SCN). The mammalian ortholog of avian gonadotropin-inhibitory hormone, RFamide-related peptide 3 (RFRP-3), participates in the circadian-timed removal of estrogen negative feedback to permit the LH surge. The present study examined the specific neurochemical means by which the SCN controls RFRP-3 activity and explored whether the RFRP-3 system exhibits time-dependent responsiveness to SCN signaling to precisely time the LH surge. We found that RFRP-3 cells in female Syrian hamsters (Mesocricetus auratus) receive close appositions from SCN-derived vasopressin-ergic and vasoactive intestinal peptide (VIP)-ergic terminal fibers. Central VIP administration markedly suppressed RFRP-3 cellular activity in the evening, but not the morning, relative to saline controls, whereas vasopressin was without effect at either time point. Double-label in situ hybridization for Rfrp-3 and the VIP receptors VPAC1 and VPAC2 revealed that the majority of RFRP-3 cells do not coexpress either receptor in Syrian hamsters or mice, suggesting that SCN VIP-ergic signaling inhibits RFRP-3 cells indirectly. The timing of this VIP-mediated disinhibition is further coordinated via temporally gated responsiveness of RFRP-3 cells to circadian signaling. Together, these findings reveal a novel circadian hierarchy of control coordinating the preovulatory LH surge and ovulation.
Consumption of a low-protein, high-carbohydrate diet induces a striking increase in circulating fibroblast growth factor-21 (FGF21), which is associated with improved cardiometabolic health and increased longevity. Increased lifespan during this dietary protein "dilution" has been explained by resource-mediated trade-offs between reproduction and survival, such that fecundity is optimized at a greater relative intake of proteins/carbohydrates. The magnitude of this trade-off is thought to be sex-dependent. In this study, we tested the hypothesis that metabolic responses to dietary protein dilution are likewise dependent on sex. We maintained age-matched adult male and female C57BL/6J mice on isocaloric diets containing 22% fat and differing in the ratio of protein/carbohydrate. The normal protein (NP) control diet contained 18% protein and 60% carbohydrate by kcal. The protein diluted (PD) diet contained 4% protein and 74% carbohydrate. Consistent with previous reports, PD males gained less weight and less fat than did normal protein controls and exhibited both improved glucose tolerance and decreased plasma lipids. In contrast, these metabolic benefits were absent among age-matched females maintained on the same diets. Likewise, whereas circulating FGF21 was increased up to 66-fold among PD male mice, this was substantially blunted among female counterparts. Sex differences in energy balance, glucose control, and plasma FGF21 were reversed upon ovariectomy. Collectively, our findings support that female mice are relatively less sensitive to the metabolic improvements observed following dietary protein dilution. This is accompanied by blunted circulating levels of FGF21 and requires an intact female reproductive system.
Introduction: The rationale for discarding the skin knife blade and replacing it with another blade for deeper dissection is to prevent bacteria that may be present on the skin from being carried into the deeper layers of the wound. This practice is very controversial because numerous, yet limited, studies exist that support and refute the findings. The purpose of this study was to directly compare the rate of contamination of a skin knife blade with a control blade. Methods: We took the surface samples using Replicate Organism Detection and Counting plates of 344 knife blades immediately after making skin incision during the following four types of orthopaedic cases: total hip arthroplasty, total knee arthroplasty, lumbar spine surgery, and cervical spine surgery. At the same time, we sampled 344 control blades. The comparison of positives skin versus control, overall and within each subgroup was done using a bivariate two-sample z-test for the equality of proportions. Results: Overall, 35 (5.1%) of the 688 specimens had a positive result. No difference was noted in the rate of positive cultures for the 344 skin blades 4.9% and the 344 control blades 5.2%. No differences were observed in the rate of positive specimens for skin blades (7.4%, 3.4%, 7.7%, and 3.9%) and control blades (2.5%, 4.1%, 7.7%, and 9.2%) for total hip arthroplasty, total knee arthroplasty, C spine, and L spine, respectively. No differences were observed regarding skin prep, room number, case order, room turnover time, or in-room to incision time. Staphylococus species was the predominant bacteria identified. Conclusion: We found no evidence to support the theoretical advantage of changing the knife blade after making skin incision to avoid contamination. Contamination rates were the same for both the skin and control blades overall and for all subgroup analysis.
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