Neural cell-types and circuits linking thermoregulation and social behavior.

Understanding how social and affective behavioral states are controlled by neural circuits is a fundamental challenge in neurobiology. Despite increasing understanding of central circuits governing prosocial and agonistic interactions, how bodily autonomic processes regulate these behaviors is less resolved. Thermoregulation is vital for maintaining homeostasis, but also associated with cognitive, physical, affective, and behavioral states. Here, we posit that adjusting body temperature may be integral to the appropriate expression of social behavior and argue that understanding neural links between behavior and thermoregulation is timely. First, changes in behavioral states-including social interaction-often accompany changes in body temperature. Second, recent work has uncovered neural populations controlling both thermoregulatory and social behavioral pathways. We identify additional neural populations that, in separate studies, control social behavior and thermoregulation, and highlight their relevance to human and animal studies. Third, dysregulation of body temperature is linked to human neuropsychiatric disorders. Although body temperature is a "hidden state" in many neurobiological studies, it likely plays an underappreciated role in regulating social and affective states.

Impact of Resuscitation Adjuncts on Post-Intubation Hypotension in Patients with Isolated TBI.

INTRODUCTION: Post-intubation hypotension (PIH) is a risk factor of endotracheal intubation (ETI) after injury. For those with traumatic brain injury (TBI), one episode of hypotension can potentiate that injury. This study aims to identify the resuscitation adjuncts which may decrease the incidence of PIH in this patient population. METHODS: This is a 4-year (2019-2022) prospective observational study at a level I trauma center. Adult (≥18) patients with isolated TBI requiring ETI in the trauma bay were included. Blood pressures were measured 15 minutes pre- and post-intubation. Primary outcome was PIH, defined as a decrease in SBP ≥ 20% from baseline or to<80 mmHg, or any decrease in MAP to ≤60 mmHg. Multivariable logistic regression was performed to identify the associations of pre-intubation vasopressor, hypertonic saline (HTS), PRBC, and crystalloids on PIH incidence. RESULTS: Of the 490 enrolled patients, 16% had mild (Head AIS ≤ 2), 35% moderate (Head AIS 3-4), and 49% severe (Head AIS ≥ 5) TBI. Mean age was 42 ± 22 years and 71% were male. Median ISS, head-AIS, and GCS were 26[19-38], 4[3-5], and 6[3-11], respectively. Mean SBP 15 minutes pre- and post-intubation were 118 ± 46 and 106 ± 45, respectively. Before intubation, 31% received HTS, 10% vasopressors, 20% crystalloids, and 14% at least one unit of PRBC (median, 2[1-2]U). Overall, 304 (62%) patients developed PIH. On multivariable regression analysis, pre-intubation use of vasopressors and HTS were associated with significantly decreased odds of PIH independent of TBI severity, 0.310 (0.102-0.944, p = 0.039) and 0.393 (0.219-0.70, p = 0.002) respectively. CONCLUSIONS: Nearly two-thirds of isolated TBI patients developed PIH. Pre-intubation vasopressors and HTS are associated with a decreased incidence of PIH. Such adjuncts should be considered prior to ETI in patients with suspected TBI. LEVEL OF EVIDENCE: III; Prospective Observational.

There Is No Such Thing as Too Soon: Long-Term Outcomes of Early Cholecystectomy for Frail Geriatric Patients with Acute Biliary Pancreatitis.

BACKGROUND: Early cholecystectomy (CCY) for acute biliary pancreatitis (ABP) is recommended but there is a paucity of data assessing this approach in frail geriatric patients. This study compares outcomes of frail geriatric ABP patients undergoing index admission CCY vs nonoperative management (NOM) with endoscopic retrograde cholangiopancreatography (ERCP). STUDY DESIGN: Retrospective analysis of the Nationwide Readmissions Database (2017). All frail geriatric (65 years or older) patients with ABP were included. Patients were grouped by treatment at index admission: CCY vs NOM with endoscopic retrograde cholangiopancreatography. Propensity score matching was performed in a 1:2 ratio. Primary outcomes were 6-month readmissions, mortality, and length of stay. Secondary outcomes were 6-month failure of NOM defined as readmission for recurrent ABP, unplanned pancreas-related procedures, or unplanned CCY. Subanalysis was performed to compare outcomes of unplanned CCY vs early CCY. RESULTS: A total of 29,130 frail geriatric patients with ABP were identified and 7,941 were matched (CCY 5,294; NOM 2,647). Patients in the CCY group had lower 6-month rates of readmission for pancreas-related complications, unplanned readmissions for pancreas-related procedures, overall readmissions, and mortality, as well as fewer hospitalized days (p < 0.05). NOM failed in 12% of patients and 7% of NOM patients were readmitted within 6 months to undergo CCY, of which 56% were unplanned. Patients who underwent unplanned CCY had higher complication rates and hospital costs, longer hospital lengths of stay, and increased mortality compared with early CCY (p < 0.05). CONCLUSIONS: For frail geriatric patients with ABP, early CCY was associated with lower 6-month rates of complications, readmissions, mortality, and fewer hospitalized days. NOM was unsuccessful in nearly 1 of 7 within 6 months; of these, one-third required unplanned CCY. Early CCY should be prioritized for frail geriatric ABP patients when feasible.

Role of Endovascular Stenting in Patients with Traumatic Iliac Artery Injury.

BACKGROUND: Common and external iliac artery injuries (IAI) portend significant morbidity and mortality. The goal of this study was to examine the impact of mechanism of injury and type of repair on outcomes and identify the optimal repair for patients with traumatic IAI using a large, national dataset. STUDY DESIGN: Patients undergoing operative repair for IAI were identified from the Trauma Quality Improvement Program database during a 5-year timespan, ending in 2019. Age, sex, race, severity of injury, severity of shock, type of iliac repair (open or endovascular), mechanism, morbidity and mortality were recorded. Patients with IAI were stratified by both type of repair and mechanism and compared. Multivariable logistic regression analysis was used to identify independent predictors of mortality. RESULTS: Operative IAI was identified in 507 patients. Of these injuries, 309 (61%) were penetrating and 346 (68.2%) involved the external iliac artery. The majority of patients were male (82%) with a median age and ISS of 31 and 20, respectively. Endovascular repair was performed in 31% of cases. For patients with penetrating injuries, the type of repair impacted neither morbidity nor mortality. For blunt-injured patients, endovascular repair was associated with lower morbidity (29.3% vs 41.3%; p = 0.082) and significantly reduced mortality (14.6% vs 26.7%; p = 0.037) compared with the open-repair approach. Multivariable logistic regression identified endovascular repair as the only modifiable risk factor associated with decreased mortality (odds ratio 0.34; 95% CI 0.15 to 0.79; p = 0.0116). CONCLUSIONS: Traumatic IAI causes significant morbidity and mortality. Endovascular repair was identified as the only modifiable predictor of decreased mortality in blunt-injured patients with traumatic IAI. Therefore, for select patients with blunt IAIs, an endovascular repair should be the preferred approach.

Transitions in paternal social status predict patterns of offspring growth and metabolic transcription.

One type of parental effect occurs when changes in parental phenotype or environment trigger changes to offspring phenotype. Such nongenetic parental effects can be precisely triggered in response to an environmental cue in time-locked fashion, or in other cases, persist for multiple generations after the cue has been removed, suggesting multiple timescales of action. For parental effects to serve as reliable signals of current environmental conditions, they should be reversible, such that when cues change, offspring phenotypes change in accordance. Social hierarchy is a prevalent feature of the environment, and current parental social status could signal the environment in which offspring will be born. Here, we sought to address parental effects of social status and their timescale of action in mice. We show that territorial competition in seminatural environments affects offspring growth. Although dominant males are not heavier than nondominant or control males, they produce faster growing offspring, particularly sons. The timing, effect-size, and sex-specificity of this association are modulated by maternal social experience. We show that a change in paternal social status is sufficient to modulate offspring weight: from one breeding cycle to the next, status-ascending males produce heavier sons than before, and status-descending males produce lighter sons than before. Current paternal status is also highly predictive of liver transcription in sons, including molecular pathways controlling oxidative phosphorylation and iron metabolism. These results are consistent with a parental effect of social experience, although alternative explanations are considered. In summary, changes in paternal social status are associated with changes in offspring growth and metabolism.

Sexual selection constrains the body mass of male but not female mice.

Sexual size dimorphism results when female and male body size is influenced differently by natural and sexual selection. Typically, in polygynous species larger male body size is thought to be favored in competition for mates and constraints on maximal body size are due to countervailing natural selection on either sex; however, it has been postulated that sexual selection itself may result in stabilizing selection at an optimal mass. Here we test this hypothesis by retrospectively assessing the influence of body mass, one metric of body size, on the fitness of 113 wild-derived house mice (Mus musculus) residing within ten replicate semi-natural enclosures from previous studies conducted by our laboratory. Enclosures possess similar levels of sexual selection, but relaxed natural selection, relative to natural systems. Heavier females produced more offspring, while males of intermediate mass had the highest fitness. Female results suggest that some aspect of natural selection, absent from enclosures, acts to decrease their body mass, while the upper and lower boundaries of male mass are constrained by sexual selection.

Reintroducing domesticated wild mice to sociality induces adaptive transgenerational effects on MUP expression.

When brought into captivity, wild animals can adapt to domestication within 10 generations. Such adaptations may decrease fitness in natural conditions. Many selective pressures are disrupted in captivity, including social behavioral networks. Although lack of sociality in captivity appears to mediate domestication, the underlying mechanisms are not well understood. Additionally, determining the contribution of genetic inheritance vs. transgenerational effects during relaxed selection may provide insight into the flexibility of adaptation. When wild-derived mice kept under laboratory conditions for eight generations were reintroduced to sociality and promiscuity (free mate choice), they adapted within two generations. Fitness assessments between this promiscuous lineage and a monogamous laboratory lineage revealed male-specific effects. Promiscuous-line males had deficits in viability, but a striking advantage in attracting mates, and their scent marks were also more attractive to females. Here, we investigate mechanistic details underlying this olfactory signal and identify a role of major urinary protein (MUP) pheromones. Promiscuous-line males inherit higher MUP expression than monogamous-line males through transgenerational inheritance. Sociality-driven maternal and paternal effects reveal intriguing conflicts among parents and offspring over pheromone expression. MUP up-regulation is not driven by hormone-driven transduction pathways, but rather is associated with reduction in DNA methylation of a CpG dinucleotide in the promoter. This reduction in methylation could enhance transcription by promoting the binding of transcription factor USF1 (upstream stimulatory factor 1). Finally, we experimentally demonstrate that increased MUP expression is a female attractant. These results identify molecular mechanisms guiding domestication and adaptive responses to fluctuating sociality.

Rapid adaptation to mammalian sociality via sexually selected traits.

BACKGROUND: Laboratory studies show that the components of sexual selection (e.g., mate choice and intrasexual competition) can profoundly affect the development and fitness of offspring. Less is known, however, about the total effects of sexual selection on offspring in normal social conditions. Complex social networks, such as dominance hierarchies, regulate the opportunity for mating success, and are often missing from laboratory studies. Social selection is an extended view of sexual selection that incorporates competition during sexual and nonsexual interactions, and predicts complex evolutionary dynamics. Whether social selection improves or constrains offspring fitness is controversial. RESULTS: To identify fitness consequences of social selection, wild-derived mice that had bred under laboratory conditions for eight generations were re-introduced to naturalistic competition in enclosures for three consecutive generations (promiscuous line). In parallel, a control lineage bred in cages under random mate assignment (monogamous line). A direct competition experiment using second-generation animals revealed that promiscuous line males had greater reproductive success than monogamous line males (particularly during extra-territorial matings), in spite of higher mortality and equivalent success in social dominance and sperm competition. There were no major female fitness effects (though promiscuous line females had fewer litters than monogamous line females). This result suggested that selection primarily acted upon a sexually attractive male phenotype in the promiscuous line, a hypothesis we confirmed in female odor and mating preference trials. CONCLUSIONS: We present novel evidence for the strength of sexual selection under normal social conditions, and show rapid male adaptation driven largely by sexual trait expression, with tradeoffs in survivorship and female fecundity. Re-introducing wild-derived mice to competition quickly uncovers sexually selected phenotypes otherwise lost in normal colony breeding.

MHC signaling during social communication.

The major histocompatibility complex (MHC) has been known to play a critical role in immune recognition since the 1950s. It was a surprise, then, in the 1970s when the first report appeared indicating MHC might also function in social signaling. Since this seminal discovery, MHC signaling has been found throughout vertebrates and its known functions have expanded beyond mate choice to include a suite of behaviors from kin-biased cooperation, parent-progeny recognition to pregnancy block. The widespread occurrence of MHC in social signaling has revealed conserved behavioral-genetic mechanisms that span vertebrates and includes humans. The identity of the signal's chemical constituents and the receptors responsible for the perception of the signal have remained elusive, but recent advances have enabled the identification of the key components of the behavioral circuit. In this chapter we organize recent findings from the literature and discuss them in relation to four nonmutually exclusive models wherein MHC functions as a signal of (i) individuality, (ii) relatedness, (iii) genetic compatibility and (iv) quality. We also synthesize current mechanistic studies, showing how knowledge about the molecular basis of MHC signaling can lead to elegant and informative experimental manipulations. Finally, we discuss current evidence relating to the primordial functions of the MHC, including the possibility that its role in social signaling may be ancestral to its central role in adaptive immunity.

Ecological immunology of bird-ectoparasite systems.

Ecological immunology is a rapidly expanding field of research that attempts to explain variation in immune function across individuals, populations and species. Birds and ectoparasitic arthropods have frequently been used in attempts to measure the cost of immune function in relation to adult condition, nestling growth and other life history challenges. Unfortunately, most studies in ecological immunology have relied on assays of general immunocompetence that are not connected to actual parasites. A summary of potential interactions between the avian immune system and ectoparasites is provided and methods that can be used to test ecological questions in the context of naturally occurring host-parasite interactions are proposed.

Sensory neurons with MHC-like peptide binding properties: disease consequences.

The recent discovery of specialized sensory neurons that bind peptides in an MHC-like fashion has revealed the long-sought odorants used to recognize the MHC genotype and phenotype of other individuals. The odorants are the same MHC peptides used during immune recognition, which provides the molecular logic linking selection acting on MHC-mediated behaviors with selection acting on immune recognition; both processes influence the evolving peptide binding properties of MHC molecules. The primary function of these chemosensory mechanisms for detecting MHC-mediated odors appears to be mating preferences (observed in humans and many vertebrates) that preferentially produce offspring more resistant to both infectious and genetic disease. Recent experiments are beginning to discriminate the relative importance of these different disease-reducing mechanisms.