Estrogen-sensitive medial preoptic area neurons coordinate torpor in mice

Homeotherms maintain a stable internal body temperature despite changing environments. During energy deficiency, some species can cease to defend their body temperature and enter a hypothermic and hypometabolic state known as torpor. Recent advances have revealed the medial preoptic area (MPA) as a key site for the regulation of torpor in mice. The MPA is estrogen-sensitive and estrogens also have potent effects on both temperature and metabolism. Here, we demonstrate that estrogen-sensitive neurons in the MPA can coordinate hypothermia and hypometabolism in mice. Selectively activating estrogen-sensitive MPA neurons was sufficient to drive a coordinated depression of metabolic rate and body temperature similar to torpor, as measured by body temperature, physical activity, indirect calorimetry, heart rate, and brain activity. Inducing torpor with a prolonged fast revealed larger and more variable calcium transients from estrogen-sensitive MPA neurons during bouts of hypothermia. Finally, whereas selective ablation of estrogen-sensitive MPA neurons demonstrated that these neurons are required for the full expression of fasting-induced torpor in both female and male mice, their effects on thermoregulation and torpor bout initiation exhibit differences across sex. Together, these findings suggest a role for estrogen-sensitive MPA neurons in directing the thermoregulatory and metabolic responses to energy deficiency.

Prisoners of Peace

As Irom Sharmila Chanu breaks her sixteen-yearlong fast on August 9, 2016, struggle for peace in India’s Northeast seems to have turned a full circle. On the one hand, her battle against the Armed Forces (Special Powers) Act 1958—the law that empowers even a noncommissioned army officer to open fire on a civilian and in the process kill her with impunity, that is to say, without ever being tried in a court of law—by all accounts made her the “iron lady” and “the Face of Manipur” to the world. On the other hand, notwithstanding her indefinite fast—widely believed to be emblematic of the “collective moral outrage” against the Act—persistent appeals made by a host of national and international human rights groups, eminent public intellectuals, and the recommendation of the respective Committees in favor of repealing it, the Act remains very much in force in parts of Jammu and Kashmir and in the Northeast even after fifty-eight years of its enactment, resulting in the death of hundreds of civilians. This article seeks to explain the implications of this paradox for peace politics in the region. Why does Sharmila have to take the otherwise painful and albeit difficult decision of breaking her fast even when there is little sign of repealing the Act? Insofar as she takes the difficult decision of breaking her fast, she realizes that her prolonged fast becomes subjected to a variety of technologies of governance: first, by calling for the complete sacrifice of her private life, second by turning her fast into a public spectacle rendering it both “unsuccessful” and necessary—significantly both at the same time—and finally by inculcating in her and in many of us the intense desire of pursuing peace through the established political institutions, particularly electoral institutions.

Perioperative blood glucose concentrations in kittens following overnight fasting and gonadectomy

Objectives The objective of this study was to determine if hypoglycemia is an effect of overnight fasting and gonadectomy in kittens, as well as to determine predictors of baseline and postoperative blood glucose. Methods This was a prospective observational study. Seventy-five kittens between the age of 8 and 16 weeks undergoing routine castration or ovariohysterectomy at an animal shelter were included. Two blood glucose measurements were analyzed per kitten after an overnight fast: a baseline reading prior to preoperative examination, and a reading immediately postoperatively. Predictors of the baseline and postoperative blood glucose levels were determined using multi-level mixed-effects linear regression. Results Kittens, when fasted overnight, were not hypoglycemic (<60 mg/dl). No kittens exhibited clinical signs consistent with hypoglycemia. No kittens had a blood glucose <70 mg/dl postoperatively. Postoperative hyperglycemia (>150 mg/dl) was observed in 44% of kittens. The only predictor of fasted blood glucose levels was body condition score. The only predictor of postoperative blood glucose levels was the fasting blood glucose value. Conclusions and relevance Overnight fasting prior to elective sterilization in 8- to 16-week-old kittens did not result in hypoglycemia. Concern regarding hypoglycemia after a prolonged fast in kittens may be unwarranted for short procedures in healthy animals.

Video capsule endoscopy: is bowel preparation necessary?

There is no standardized protocol for bowel preparation prior to video capsule endoscopy, although one is strongly recommended. The purpose of our study was to see if there was a statistical significance between small bowel mucosal visualization rates for those who received bowel preparation and those who did not. We retrospectively analyzed all patients who had a video capsule endoscopy from August 2014 to January 2016 at a tertiary care center. All patients fasted prior to the procedure. Bowel preparation when used consisted of polyethylene glycol. A long fast consisted of 12 or more hours. The grading system used to assess the small bowel was adapted from a previously validated system from Esaki et al. Statistical analyses were performed using Fisher's exact test or Welch's 2-sample t-test and statistical significance was present if the p value was ≤0.05. 76 patients were carried forward for analysis. Small bowel mucosal visualization rates were similar between those who received bowel preparation and those who did not (92.5% vs 88.9%, p=0.44). Small bowel mucosal visualization rates were significantly better in those patients who had a long fast compared with those who had a short fast (97.7% vs 81.3%, p=0.019). Our study demonstrates that the addition of bowel preparation prior to video capsule endoscopy does not significantly improve small bowel mucosal visualization rates and, in addition, there is a statistically significant relationship between increased fasting time and improved small bowel mucosal visualization. A prolonged fast without bowel preparation might be satisfactory for an adequate small bowel visualization but further randomized, prospective studies are necessary to confirm these findings.

Refeeding-Activated Glutamatergic Neurons in the Hypothalamic Paraventricular Nucleus (PVN) Mediate Effects of Melanocortin Signaling in the Nucleus Tractus Solitarius (NTS)

We previously demonstrated that refeeding after a prolonged fast activates a subset of neurons in the ventral parvocellular subdivision of the paraventricular nucleus (PVNv) as a result of increased melanocortin signaling. To determine whether these neurons contribute to satiety by projecting to the nucleus tractus solitarius (NTS), the retrogradely transported marker substance, cholera toxin-β (CTB), was injected into the dorsal vagal complex of rats that were subsequently fasted and refed for 2 h. By double-labeling immunohistochemistry, CTB accumulation was found in the cytoplasm of the majority of refeeding-activated c-Fos neurons in the ventral parvocellular subdivision of the hypothalamic paraventricular nucleus (PVNv). In addition, a large number of refeeding-activated c-Fos-expressing neurons were observed in the lateral parvocellular subdivision (PVNl) that also contained CTB and were innervated by axon terminals of proopiomelanocortin neurons. To visualize the location of neuronal activation within the NTS by melanocortin-activated PVN neurons, α-MSH was focally injected into the PVN, resulting in an increased number of c-Fos-containing neurons in the PVN and in the NTS, primarily in the medial and commissural parts. All refeeding-activated neurons in the PVNv and PVNl expressed the mRNA of the glutamatergic marker, type 2 vesicular glutamate transporter (VGLUT2), indicating their glutamatergic phenotype, but only rare neurons contained oxytocin. These data suggest that melanocortin-activated neurons in the PVNv and PVNl may contribute to refeeding-induced satiety through effects on the NTS and may alter the sensitivity of NTS neurons to vagal satiety inputs via glutamate excitation.