Reproduction and thermoregulation in Peromyscus: Effects of chronic short days

Seven groups of laboratory reared Connecticut P. leucopus were exposed to a 9L:15D photoperiod for either 6, 9, 12, 20, 25, 32, or 36 weeks. An eighth group was maintained on 16L:8D. During the final 6 weeks all mice were cold exposed (13°C). Substantial reproductive regression occurred in females following 6 weeks exposure to 9L:15D relative to 16L:8D animals. In males, a slight decrease in testicular weight occurred following 6 weeks on 9L:15D; this effect was pronounced by 9 weeks, along with a decrease in seminal vesicle weight. Reproductive recrudescence occurred in females by week 32 and in males by week 36. Between 10 and 12 weeks on 9L:15D mice exhibited increases in nesting, incidence of daily torpor, and presence of the winter molt. These increases persisted through 36 weeks on 9L:15D. An increase in the interscapular brown fat pad occurred between 12 and 25 weeks. Reproductive and thermoregulatory characters respond differently to prolonged exposure to a short day photoperiod in this species.     

Photoperiod, temperature and melatonin effects on thermoregulatory behavior in Djungarian hamsters

Nesting and burrowing activity were measured in hamsters acclimated to either long or short day photoperiod in thermoneutrality and at 10 degrees C. Hamsters build larger nests under short day photoperiod or at 10 degrees C as compared to long day photoperiod or thermoneutrality. Both environmental cues contributed about 50% to a total increase in nest size from 1.8 g cotton/day to 7.7 g cotton/day (long day thermoneutral versus short day at 10 degrees C). Burrowing activity was suppressed by both cold or short day exposure. Daily melatonin injections, effective in inducing physiological short day adjustment under a long day photoperiod, also increased nesting scores. Hamsters which did not respond to short day conditions or to melatonin treatment physiologically lacked behavioral adjustments as well. Collectively, these results demonstrate analogies in the environmental control of physiological thermoregulatory adjustment and nesting behavior. Burrowing activity seems to be more related to reproductive needs than to thermoregulatory requirements in this hamster.     

Novel germline p16(INK4) allele (Asp145Cys) in a family with multiple pancreatic carcinomas. Mutations in brief no. 148. Online

As part of a search for causative genes of familial pancreatic carcinoma, the p16 genes were sequenced in members of 21 families with a phenotype of familial pancreatic carcinoma (2 or more first degree relatives affected). One family was found in which members carried a novel p16 allele with a G to T transversion at position 451, creating a missense amino acid change at codon 145 (Asp to Cys) and possibly disrupting the donor splice site of the exon 2/3 boundary. This coding change is not a known polymorphism, and occurs at a codon position in which another missese/splicing change has been shown to be linked to familial melanoma/pancreas cancer.     

Absence of a daily neuronal rhythm in the suprachiasmatic nuclei of acircadian Djungarian hamsters.

The suprachiasmatic nuclei (SCN) in mammals generate and maintain a variety of daily rhythms. In nocturnally active rodents, SCN electrical activity is high during the subjective day (that time of locomotor inactivity) and low during the subjective night. The present experiment examines the relationship between SCN neuronal activity and the expression of overt circadian behavior in the Djungarian hamster (Phodopus sungorus). Wheel-running locomotor activity was measured in 2 groups of hamsters housed in constant dark (DD). Twelve hamsters, selected from ongoing experiments in our laboratory, showed no overt circadian rhythm in locomotor activity. A second group of 9 control animals exhibited rhythmic wheel-running activity in DD. In contrast to control animals, in vitro SCN electrical activity in brain slices prepared from acircadian hamsters showed no circadian variation. These data indicate that in acircadian animals SCN electrical activity properly reflects behavioral patterns.     

Autoradiographic localization of kappa opiate receptors in CNS taste and feeding areas

Recent evidence suggests that kappa opiate receptors may play a key role in the regulation of appetite. Such evidence implies that kappa receptors might be localized within specific brain areas known to regulate ingestive behaviors. On the basis of this implication we employed an in vitro film autoradiographic technique using 3H-ethylketocyclazozine as ligand to identify putative kappa receptors within CNS "taste" nuclei and surrounding areas. Coronal cryostat sections of rat brain were incubated with ligand in the presence of D-Ala2, D-Leu5-enkephalin (DADLE) and morphine, apposed to LKB Ultrofilm for 60 days, processed and kappa receptor densities evaluated with the aid of a hand held photometer and video image analyzer. Highest kappa receptor densities were found within various gustatory and feeding sites including the rostral pole of the nucleus of the solitary tract, parabrachial nuclei, ventral posterior and medial portions of the thalamus, medial hypothalamus, medial nuclei of the amygdala and bed nucleus of the stria terminalis. Various other midline and medial limbic areas also showed significant kappa densities.     

Recognition and treatment of patients with hereditary nonpolyposis colon cancer (Lynch syndromes I and II).

Primary genetic factors are etiologic in at least 5-10% of patients with colon cancer. The polyposis syndromes (FPC) are easily identified examples because of the spectacular number of polyps. The hereditary nonpolyposis syndromes (HNPCC), although five times more common than FPC, are usually not recognized because they do not have such a distinctive clinical, premonitory genetic marker. Colorectal cancer expression was surveyed in 10 extended, thoroughly documented HNPCC kindreds. One hundred sixteen patients were found to have 183 colorectal cancers. Despite the striking family history, less than 5% were correctly treated by subtotal colectomy. This provided a unique opportunity to study the natural history. Five findings differed significantly (p less than 0.05) from patients with sporadic colon cancer: (1) mean age of initial colon cancer diagnosed was 45.6 years; (2) 69.1% of first colon cancers were located proximal to the splenic flexure of the colon; (3) 18.1% had synchronous colon cancer; (4) 24.2% had metachronous colon cancer develop with life table analysis showing the risk for a metachronous lesion at 10 years to be 40%; and (5) only 23.3% of cancers were located in the sigmoid colon or rectum. Based on this data, it is recommended that the family history of all patients with a newly diagnosed colon cancer be evaluated for evidence of this syndrome. If an autosomal dominant inheritance pattern emerges, an in-depth genetic investigation is indicated. When HNPCC is confirmed, the following recommendations apply: a subtotal abdominal colectomy is indicated at the time of the initial colon cancer because of the risk of synchronous and metachronous lesions. The rectum should be spared in favor of careful lifetime surveillance because of the proclivity for proximal colon cancer involvement. As yet unaffected members of a newly diagnosed HNPCC kindred who are in the "direct genetic line" should be cautioned that they are at 50% risk and must begin an intensive surveillance program beginning in the third decade with careful attention to the right colon. Patients from newly diagnosed HNPCC families who have had a previous conventional colectomy for colon cancer should, at the very least, enter an intensive surveillance program; a prophylactic completion subtotal colectomy should be considered for patients who are less than totally compliant.     

Kidney transplant program waitlisting rate as a metric to assess transplant access

Kidney transplant program performance in the United States is commonly measured by posttransplant outcomes. Inclusion of pretransplant measures could provide a more comprehensive assessment of transplant program performance and necessary information for patient decision-making. In this study, we propose a new metric, the waitlisting rate, defined as the ratio of patients who are waitlisted in a center relative to the person-years referred for evaluation to a program. Furthermore, we standardize the waitlisting rate relative to the state average in Georgia, North Carolina, and South Carolina. The new metric was used as a proof-of-concept to assess transplant-program access compared to the existing transplant rate metric. The study cohorts were defined by linking 2017 United States Renal Data System (USRDS) data with transplant-program referral data from the Southeastern United States between January 1, 2012 and December 31, 2016. Waitlisting rate varied across the 9 Southeastern transplant programs, ranging from 10 to 22 events per 100 patient-years, whereas the program-specific waitlisting rate ratio ranged between 0.76 and 1.33. Program-specific waitlisting rate ratio was uncorrelated with the transplant rate ratio (r = −.15, 95% CI, −0.83 to 0.57). Findings warrant collection of national data on early transplant steps, such as referral, for a more comprehensive assessment of transplant program performance and pretransplant access.     

Public discourse and policy change: Absence of harm from increased oversight and transparency in OPO performance

The Centers for Medicare and Medicaid Services announced changes to the Final Rule for organ procurement organizations (OPOs) in November 2020, after a 23-month period of public debate. One concern among transplant stakeholders was that public focus on OPO underperformance would harm deceased donation. Using CDC-WONDER data, we studied whether donation performance dropped during the era of public debate about OPO reform (December 2018–February 2020). Overall OPO performance as measured relative to cause, age, and location-consistent deaths rose by 12.3% in 2019, compared to a median annual change of 2.5% 2009–2019. Organ recoveries exceeded seasonally adjusted forecasts by 4.2% in the first half of 2019, by 8.1% following the Executive Order issuing a mandate for OPO metric reform, and by 14.1% between the Notice of Public Rule Making and the onset of COVID-19-related systemic disruptions. We describe changes in donor phenotype in the period of increased performance; improvement was greatest for older and donation after cardiac death (DCD) donors, and among decedents who did not have a drug-related mechanism of death. In summary, performance during an era of intense public debate and proposed regulatory changes yielded 692 additional donors over expectations, and no detriment to organ donation was observed.