Foot Injuries in Michigan, USA, Gray Wolves (\u3ci\u3eCanis lupus\u3c/i\u3e), 1992–2014

The range of gray wolves (Canis lupus) in the contiguous US is expanding. Research and monitoring to support population recovery and management often involves capture via foothold traps. A population-level epidemiologic assessment of the effect of trap injuries on wolf survival remains needed to inform management. We describe the baseline rate, type, and severity of foot injuries of wolves born 1992–2013 in Michigan’s Upper Peninsula, evaluate the reliability of field-scoring trap-related injuries, and the effect of injuries on wolf survival. We assessed foot injuries by physical and radiographic exam at postmortem and/or time of capture for 351 wolves using the International Organization for Standardization 10990-5 standard and the effects of injuries, sex, age, previous capture and body condition on survival using proportional hazards regression. We used ordinal regression to evaluate epidemiologic associations between sex, age, previous capture, body condition, cause of death and injury severity. Most wolves (53%) experienced no physically or radiographically discernable foot injuries over their lifetimes. Among those wolves that did experience injuries, 33% scored as mild. Foot injuries had little epidemiologically discernable effect on survival rates. Wolves with higher foot trauma scores did experience an increased risk of dying, but the magnitude of the increase was modest. Most limb injuries occurred below the carpus or tarsus, and scoring upper-limb injuries added little predictive information to population-level epidemiologic measures of survival and injury severity. There was little association between injury severity and cause of death. Based on necropsy exams, previous trap injuries likely contributed to death in only four wolves (1.1%). Our results suggest that injuries resulting from foothold traps are unlikely to be a limiting factor in recovery and ongoing survival of the Michigan gray wolf population

Chemical dissociation of human awareness: focus on non-competitive NMDA receptor antagonists

Since the mid-1950s the pharmaceutical industry has developed a number of chemicals, including phencyclidine, ketamine and related arylcyclohexylamines (PCE and TCP), dizocilpine (MK-801), N-allylnormetazocine [ NANM, (±)SKF-10,047], etoxadrol, dioxadrol and its enantiomers dexoxadrol and levoxadrol, which produce a constellation of unusual behavioral effects in animals and man. The compounds best studied in humans are phencyclidine and ketamine. They produce a remarkable dose-dependent dissociation of awareness. All of these substances are now known to be non-competitive antagonists of NMDA receptors of glutamic acid. They act in the NMDA receptor ion channel. One can conclude, on the basis of the effects observed with these agents, that glutamic acid and related excitatory amino acids are extremely important in the maintenance of human awareness.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68872/2/10.1177_026988119200600312.pd

Acute visceral pain relief mediated by A(3)AR agonists in rats: involvement of N-type voltage-gated calcium channels

Pharmacological tools for chronic visceral pain management are still limited and inadequate. A(3) adenosine receptor (A(3)AR) agonists are effective in different models of persistent pain. Recently, their activity has been related to the block of N-type voltage-gated Ca(2+) channels (Ca(v)2.2) in dorsal root ganglia (DRG) neurons. The present work aimed to evaluate the efficacy of A(3)AR agonists in reducing postinflammatory visceral hypersensitivity in both male and female rats. Colitis was induced by the intracolonic instillation of 2,4-dinitrobenzenesulfonic acid (DNBS; 30 mg in 0.25 mL 50% EtOH). Visceral hypersensitivity was assessed by measuring the visceromotor response and the abdominal withdrawal reflex to colorectal distension. The effects of A(3)AR agonists (MRS5980 and Cl-IB-MECA) were evaluated over time after DNBS injection and compared to that of the selective Ca(v)2.2 blocker PD173212, and the clinically used drug linaclotide. A(3)AR agonists significantly reduced DNBS-evoked visceral pain both in the postinflammatory (14 and 21 days after DNBS injection) and persistence (28 and 35 days after DNBS) phases. Efficacy was comparable to effects induced by linaclotide. PD173212 fully reduced abdominal hypersensitivity to control values, highlighting the role of Ca(v)2.2. The effects of MRS5980 and Cl-IB-MECA were completely abolished by the selective A(3)AR antagonist MRS1523. Furthermore, patch-clamp recordings showed that A(3)AR agonists inhibited Ca(v)2.2 in dorsal root ganglia neurons isolated from either control or DNBS-treated rats. The effect on Ca(2+) current was PD173212-sensitive and prevented by MRS1523. A(3)AR agonists are effective in relieving visceral hypersensitivity induced by DNBS, suggesting a potential therapeutic role against abdominal pain

How payment for research participation can be coercive

The idea that payment for research participation can be coercive appears widespread among research ethics committee members, researchers, and regulatory bodies. Yet analysis of the concept of coercion by philosophers and bioethicists has mostly concluded that payment does not coerce, because coercion necessarily involves threats, not offers. In this article we aim to resolve this disagreement by distinguishing between two distinct but overlapping concepts of coercion. Consent- undermining coercion marks out certain actions as impermissible and certain agreements as unenforceable. By contrast, coercion as subjection indicates a way in which someone’s interests can be partially set back in virtue of being subject to another’s foreign will. While offers of payment do not normally constitute consent-undermining coercion, they do sometimes constitute coercion as subjection. We offer an analysis of coercion as subjection and propose three possible practical responses to worries about the coerciveness of payment

Rising incidence of breast cancer among female cancer survivors: implications for surveillance

The number of female cancer survivors has been rising rapidly. We assessed the occurrence of breast cancer in these survivors over time. We computed incidence of primary breast cancer in two cohorts of female cancer survivors with a first diagnosis of cancer at ages 30+ in the periods 1975–1979 and 1990–1994. Cohorts were followed for 10 years through a population-based cancer registry. Over a period of 15 years, the incidence rate of breast cancer among female cancer survivors increased by 30% (age-standardised rate ratio (RR-adj): 1.30; 95% CI: 1.03–1.68). The increase was significant for non-breast cancer survivors (RR-adj: 1.41, 95% CI: 1.04–2.75). During the study period, the rate of second breast cancer stage II tripled (RR-adj: 3.10, 95% CI: 1.73–5.78). Non-breast cancer survivors had a significantly (P value=0.005) more unfavourable stage distribution (62% stage II and III) than breast cancer survivors (32% stage II and III). A marked rise in breast cancer incidence among female cancer survivors was observed. Research to optimise follow-up strategies for these women to detect breast cancer at an early stage is warranted

Histological type and grade of breast cancer tumors by parity, age at birth, and time since birth: a register-based study in Norway

<p>Abstract</p> <p>Background</p> <p>Some studies have indicated that reproductive factors affect the risk of histological types of breast cancer differently. The long-term protective effect of a childbirth is preceded by a short-term adverse effect. Few studies have examined whether tumors diagnosed shortly after birth have specific histological characteristics.</p> <p>Methods</p> <p>In the present register-based study, comprising information for 22,867 Norwegian breast cancer cases (20-74 years), we examined whether histological type (9 categories) and grade of tumor (2 combined categories) differed by parity or age at first birth. Associations with time since birth were evaluated among 9709 women diagnosed before age 50 years. Chi-square tests were applied for comparing proportions, whereas odds ratios (each histological type vs. ductal, or grade 3-4 vs. grade 1-2) were estimated in polytomous and binary logistic regression analyses.</p> <p>Results</p> <p>Ductal tumors, the most common histological type, accounted for 81.4% of all cases, followed by lobular tumors (6.3%) and unspecified carcinomas (5.5%). Other subtypes accounted for 0.4%-1.5% of the cases each. For all histological types, the proportions differed significantly by age at diagnoses. The proportion of mucinous and tubular tumors decreased with increasing parity, whereas Paget disease and medullary tumors were most common in women of high parity. An increasing trend with increasing age at first birth was most pronounced for lobular tumors and unspecified carcinomas; an association in the opposite direction was seen in relation to medullary and tubular tumors. In age-adjusted analyses, only the proportions of unspecified carcinomas and lobular tumors decreased significantly with increasing time since first and last birth. However, ductal tumors, and malignant sarcomas, mainly phyllodes tumors, seemed to occur at higher frequency in women diagnosed <2 years after first childbirth. The proportions of medullary tumors and Paget disease were particularly high among women diagnosed 2-5 years after last birth. The high proportion of poorly differentiated tumors in women with a recent childbirth was partly explained by young age.</p> <p>Conclusion</p> <p>Our results support previous observations that reproductive factors affect the risk of histological types of breast cancer differently. Sarcomas, medullary tumors, and possible also Paget disease, may be particularly susceptible to pregnancy-related exposure.</p

Gap junctions in olfactory neurons modulate olfactory sensitivity

<p>Abstract</p> <p>Background</p> <p>One of the fundamental questions in olfaction is whether olfactory receptor neurons (ORNs) behave as independent entities within the olfactory epithelium. On the basis that mature ORNs express multiple connexins, I postulated that gap junctional communication modulates olfactory responses in the periphery and that disruption of gap junctions in ORNs reduces olfactory sensitivity. The data collected from characterizing connexin 43 (Cx43) dominant negative transgenic mice OlfDNCX, and from calcium imaging of wild type mice (WT) support my hypothesis.</p> <p>Results</p> <p>I generated OlfDNCX mice that express a dominant negative Cx43 protein, Cx43/β-gal, in mature ORNs to inactivate gap junctions and hemichannels composed of Cx43 or other structurally related connexins. Characterization of OlfDNCX revealed that Cx43/β-gal was exclusively expressed in areas where mature ORNs resided. Real time quantitative PCR indicated that cellular machineries of OlfDNCX were normal in comparison to WT. Electroolfactogram recordings showed decreased olfactory responses to octaldehyde, heptaldehyde and acetyl acetate in OlfDNCX compared to WT. Octaldehyde-elicited glomerular activity in the olfactory bulb, measured according to odor-elicited <it>c-fos </it>mRNA upregulation in juxtaglomerular cells, was confined to smaller areas of the glomerular layer in OlfDNCX compared to WT. In WT mice, octaldehyde sensitive neurons exhibited reduced response magnitudes after application of gap junction uncoupling reagents and the effects were specific to subsets of neurons.</p> <p>Conclusions</p> <p>My study has demonstrated that altered assembly of Cx43 or structurally related connexins in ORNs modulates olfactory responses and changes olfactory activation maps in the olfactory bulb. Furthermore, pharmacologically uncoupling of gap junctions reduces olfactory activity in subsets of ORNs. These data suggest that gap junctional communication or hemichannel activity plays a critical role in maintaining olfactory sensitivity and odor perception.</p

Pregnancy-related factors and the risk of breast carcinoma in situ and invasive breast cancer among postmenopausal women in the California Teachers Study cohort

Abstract Introduction Although pregnancy-related factors such as nulliparity and late age at first full-term pregnancy are well-established risk factors for invasive breast cancer, the roles of these factors in the natural history of breast cancer development remain unclear. Methods Among 52,464 postmenopausal women participating in the California Teachers Study (CTS), 624 were diagnosed with breast carcinoma in situ (CIS) and 2,828 with invasive breast cancer between 1995 and 2007. Multivariable Cox proportional hazards regression methods were used to estimate relative risks associated with parity, age at first full-term pregnancy, breastfeeding, nausea or vomiting during pregnancy, and preeclampsia. Results Compared with never-pregnant women, an increasing number of full-term pregnancies was associated with greater risk reduction for both breast CIS and invasive breast cancer (both P trend &lt; 0.01). Women having four or more full-term pregnancies had a 31% lower breast CIS risk (RR = 0.69, 95% CI = 0.51 to 0.93) and 18% lower invasive breast cancer risk (RR = 0.82, 95% CI = 0.72 to 0.94). Parous women whose first full-term pregnancy occurred at age 35 years or later had a 118% greater risk for breast CIS (RR = 2.18, 95% CI = 1.36 to 3.49) and 27% greater risk for invasive breast cancer (RR = 1.27, 95% CI = 0.99 to 1.65) than those whose first full-term pregnancy occurred before age 21 years. Furthermore, parity was negatively associated with the risk of estrogen receptor-positive (ER+) or ER+/progesterone receptor-positive (PR+) while age at first full-term pregnancy was positively associated with the risk of ER+ or ER+/PR+ invasive breast cancer. Neither of these factors was statistically significantly associated with the risk of ER-negative (ER-) or ER-/PR- invasive breast cancer, tests for heterogeneity between subtypes did not reach statistical significance. No clear associations were detected for other pregnancy-related factors. Conclusions These results provide some epidemiologic evidence that parity and age at first full-term pregnancy are involved in the development of breast cancer among postmenopausal women. The role of these factors in risk of in situ versus invasive, and hormone receptor-positive versus -negative breast cancer merits further exploration