Apoptosis-Inducing-Factor-Dependent Mitochondrial Function Is Required for T Cell but Not B Cell Function.

The role of apoptosis inducing factor (AIF) in promoting cell death versus survival remains controversial. We report that the loss of AIF in fibroblasts led to mitochondrial electron transport chain defects and loss of proliferation that could be restored by ectopic expression of the yeast NADH dehydrogenase Ndi1. Aif-deficiency in T cells led to decreased peripheral T cell numbers and defective homeostatic proliferation, but thymic T cell development was unaffected. In contrast, Aif-deficient B cells developed and functioned normally. The difference in the dependency of T cells versus B cells on AIF for function and survival correlated with their metabolic requirements. Ectopic Ndi1 expression rescued homeostatic proliferation of Aif-deficient T cells. Despite its reported roles in cell death, fibroblasts, thymocytes and B cells lacking AIF underwent normal death. These studies suggest that the primary role of AIF relates to complex I function, with differential effects on T and B cells.

Morphological Features Among Gaussian, Sagittal, and Tangential Curvature Maps in Normal and Keratoconus Eyes Using Anterior Segment Optical Coherence Tomography.

PURPOSE: To investigate and compare the morphological features and differences among Gaussian, Sagittal, and Tangential anterior corneal curvature maps obtained with an anterior segment optical coherence tomographer combined with a Placido disc MS-39 device in keratoconus (KC) and normal eyes. METHODS: Prospective, cross-sectional study including 37 KC and 51 healthy eyes. The pattern of astigmatism and maximum keratometry (Kmax), keratometry at the thinnest point (Ktp) and 2 mm diameter (K 2mm ), and inferior-superior dioptric asymmetry values were obtained and calculated from Gaussian, Tangential, and Sagittal curvature maps using the MS-39 (CSO). RESULTS: In KC eyes, an asymmetric bowtie pattern was observed in 64.86% (24/37), 64.86% (24/37), and 0% in the Sagittal, Tangential, and Gaussian maps, respectively. In normal eyes, 51.0% (26/51), 51.0% (26/51), and 0% showed a symmetric bowtie pattern in the Sagittal, Tangential, and Gaussian maps, respectively. There was a significant difference for the variables Kmax, Ktp, and K 2mm inferior among the Gaussian, Tangential, and Sagittal maps in both normal and KC groups. Sensitivity discriminating between normal and KC eyes was 100%, 97.3%, and 90.9% and specificity was 94.1%, 100%, and 100% for Kmax coming from the Tangential, Gaussian, and Sagittal maps, respectively. CONCLUSIONS: Gaussian maps displayed significantly different morphological features when compared with Sagittal and Tangential maps in normal and KC eyes. Anterior curvature maps from Gaussian maps do not show the morphological pattern of symmetric bowtie in normal eyes nor asymmetric bowtie in KC eyes. Kmax from Gaussian maps are more specific, however less sensitive than Tangential maps in discriminating KC from normal eyes.

Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate- and high-risk early-stage triple-negative breast cancer.

BACKGROUND: Post-treatment detection of circulating tumour DNA (ctDNA) in early-stage triple-negative breast cancer (TNBC) patients predicts high risk of relapse. c-TRAK TN assessed the utility of prospective ctDNA surveillance in TNBC and the activity of pembrolizumab in patients with ctDNA detected [ctDNA positive (ctDNA+)]. PATIENTS AND METHODS: c-TRAK TN, a multicentre phase II trial, with integrated prospective ctDNA surveillance by digital PCR, enrolled patients with early-stage TNBC and residual disease following neoadjuvant chemotherapy, or stage II/III with adjuvant chemotherapy. ctDNA surveillance comprised three-monthly blood sampling to 12 months (18 months if samples were missed due to coronavirus disease), and ctDNA+ patients were randomised 2 : 1 to intervention : observation. ctDNA results were blinded unless patients were allocated to intervention, when staging scans were done and those free of recurrence were offered pembrolizumab. A protocol amendment (16 September 2020) closed the observation group; all subsequent ctDNA+ patients were allocated to intervention. Co-primary endpoints were (i) ctDNA detection rate and (ii) sustained ctDNA clearance rate on pembrolizumab (NCT03145961). RESULTS: Two hundred and eight patients registered between 30 January 2018 and 06 December 2019, 185 had tumour sequenced, 171 (92.4%) had trackable mutations, and 161 entered ctDNA surveillance. Rate of ctDNA detection by 12 months was 27.3% (44/161, 95% confidence interval 20.6% to 34.9%). Seven patients relapsed without prior ctDNA detection. Forty-five patients entered the therapeutic component (intervention n = 31; observation n = 14; one observation patient was re-allocated to intervention following protocol amendment). Of patients allocated to intervention, 72% (23/32) had metastases on staging at the time of ctDNA+, and 4 patients declined pembrolizumab. Of the five patients who commenced pembrolizumab, none achieved sustained ctDNA clearance. CONCLUSIONS: c-TRAK TN is the first prospective study to assess whether ctDNA assays have clinical utility in guiding therapy in TNBC. Patients had a high rate of metastatic disease on ctDNA detection. Findings have implications for future trial design, emphasising the importance of commencing ctDNA testing early, with more sensitive and/or frequent ctDNA testing regimes.

Role of cytosolic carbonic anhydrase Ca17a in cardiorespiratory responses to CO2 in developing zebrafish (Danio rerio).

The sensing of environmental fluctuations and initiation of appropriate physiological responses is crucial to homeostasis. Neuroepithelial cells (NECs) in fishes are putative chemoreceptors, resembling mammalian Type I (glomus) cells, that respond in vitro to changes in O2, CO2, NH3, and pH. Cytosolic carbonic anhydrase (Ca17a) is thought to be involved in CO2 sensing owing to its presence in NECs. Zebrafish (Danio rerio) lacking functional Ca17a were generated via CRISPR/Cas9 technology and used to assess the role of Ca17a in initiating the cardiorespiratory responses to elevated CO2 (hypercapnia). Unfortunately, the homozygous knockout mutants (ca17a-/-) did not survive more than ∼12-14 days postfertilization (dpf), restricting experiments to early developmental stages (4-8 dpf). Changes in ventilation (fV) and cardiac (fH) frequency in response to hypercapnia (1% CO2) in wild-type (ca17a+/+), heterozygous (ca17a+/-) and ca17a-/- fish were used to investigate Ca17a-dependent CO2 sensing and downstream signaling. Wild-type fish exhibited hyperventilation during hypercapnia as indicated by an increase in fV. In the ca17a-/- fish, the hyperventilatory response was attenuated markedly but only at 8 dpf. Hypercapnic tachycardia was observed for all genotypes and did not appear to be influenced by the absence of Ca17a. Interestingly, ca17a-/- fish exhibited a significantly lower resting fH that became more pronounced as the fish aged. The decrease in resting fH was prevented ("rescued") when ca17a-/- embryos were injected with ca17a mRNA. Collectively, the results of this study support a role for Ca17a in promoting hyperventilation during hypercapnia in larval zebrafish and suggest a previously unrecognized role for Ca17a in determining resting heart rate.

Repeatability of Corneal Deformation Response Parameters by Dynamic Ultra High-speed Scheimpflug Imaging in Normal and Keratoconus Eyes.

PURPOSE: To assess the repeatability of corneal dynamic response (CDR) parameters in normal and keratoconus (KC) eyes using ultra high-speed Scheimpflug imaging. METHODS: Prospective, comparative, observational study, including eyes of 112 patients that underwent high-speed Scheimpflug imaging analysis (Corvis ST, OCULUS). Twenty-one CDR parameters were evaluated to asses repeatability using: coefficient of repeatability (CR), coefficient of variation, intraclass correlation coefficient (ICC) and within-subject SD. Three consecutive measurements by the same operator were performed for each eye. RESULTS: There were no significant differences between the three consecutive measurements for all parameters in both normal and KC eyes. 71.42% (15 of the 21 parameters evaluated) and 85.71% (18 of the 21 parameters) were highly repeatable in the normal and KC group, respectively. The tomographic biomechanical index (TBI), corneal biomechanical index (CBI), and stiffness parameter (SPA1) showed an ICC of 0.978, 0.954, and 0.958 in normal and 0.982, 0.892, and 0.978 in KC eyes, respectively. The CR in normal eyes for TBI, CBI, and SPA1 were 0.169, 0.242, and 14.12, respectively, and for KC eyes 0.06, 0.23, and 13.64, respectively. CONCLUSIONS: Most of the corneal dynamic response parameters were highly repeatable in normal and KC eyes.

How to Be An Antiracist Hand Surgery Educator.

Racism that unjustly marginalizes black people in the United States is not a new concept. It underlies nearly every aspect of American history, leading to the systemic racism that is ingrained in our society today. With the recurrent theme of people of color having worse health outcomes than the majority community, it is important for hand surgeons to employ cultural competence and antiracist education to provide better care and support for patients, staff, students, and colleagues. In this article, we will provide a definitional framework, clinical examples, and practical pearls to promote change. To reduce racial and ethnic health care inequities and diversify the field of hand surgery, we must advocate on behalf of black and brown colleagues, staff, students, and/or friends to address racist policies and procedures.

Racial and Gender Discrimination in Hand Surgery Letters of Recommendation.

PURPOSE: We sought to evaluate hand surgery applicants' letters of recommendations to understand whether applicant and letter writer demographics contribute to racial and gender bias. METHODS: All applications submitted through the American Society for Surgery of the Hand match to a single institution fellowship program for the 2017 to 2019 application cycles were analyzed using validated text analysis software. Race/ethnicity information was derived from an analysis of applicant photos using the Face Secret Pro software. Primary outcome measures were differences in communal and agentic language used in letters of recommendation, stratified by both race/ethnicity and gender. RESULTS: A total of 912 letters of recommendation were analyzed for 233 applicants (51 female and 172 male). Of these, 88 were written by female letter writers and 824 were written by male letter writers. There were 8 Black, 12 Hispanic, 36 Asian, and 167 White applicants. Letter writers used more agentic language with Asian applicants and non-White applicants overall. Female letter writers used more communal terms and were not associated with applicant race or gender. CONCLUSIONS: Letters of recommendation in hand surgery demonstrate disparities in language based on race and gender. CLINICAL RELEVANCE: Alerting letter writers to the role of implicit bias will hopefully spur a discussion on tools to mitigate the use of biased language and provide a foundation for an equitable selection process. Efforts to improve policies and procedures pertaining to diversity and inclusion are paramount to ensuring that fellows more completely represent the population hand surgeons wish to serve.

The Impact of Palatal Fistulae on the Success of Alveolar Bone Grafting.

ABSTRACT: Palatal fistulae are common complications of cleft palate surgery with a frequency of 5% to 29% and are challenging to repair. Optimal timing to repair palatal fistulae, in a staged fashion before alveolar bone grafting, or at the same time, still remains controversial. The primary aim of this study is to compare outcomes of 2 groups with regard to successful alveolar bone grafting in patients with cleft lip and palate and palatal fistulae. We describe a review of 85 consecutive patients identified as undergoing bone grafting from a single institution craniofacial team during 2003 to 2018. Twenty-eight required palatal fistula repair. All patients had a diagnosis of unilateral or bilateral complete cleft lip and palate. Patients with cleft lip and palate repairs were stratified based on preoperative or simultaneous palatal fistula repair. Panoramic radiographs were reviewed by 2 physicians to evaluate success of bone grafting. Comparison between cohorts was made by statistical analysis. Of the 28 that required palatal fistula repair, 15 (53.6%) patients underwent prebone grafting palatal fistula repair and 13 (46.4%) patients underwent simultaneous bone grafting with palatal fistula repair. Mean age at time of bone grafting and palatal fistula repair were 10.60 years old and 9.39 years old, respectively. Length to follow-up was 54.82 months. The average height of the healed alveolar cleft site for patients in the prebone grafting or simultaneous groups was 10.57 mm and 11.46 mm, respectively. Patients who underwent palatal fistula repair and simultaneous bone grafting had similar outcomes as those with palatal fistula repair preoperatively.

Evolution of Surgical Management of Sagittal Synostosis.

ABSTRACT: Numerous methods for surgical correction of sagittal synostosis have been described in the literature, yielding similar outcomes. At the authors' institution, surgical approaches to correct this condition have evolved over the past few decades, including Π, H-type craniectomies (Renier), endoscopic suturectomy, and our current technique, the FLAG procedure. Our aim is to review the evolution of these surgical techniques at our institution and compare patient outcomes. A retrospective review was performed on consecutive patients undergoing correction for craniosynostosis from 2008 to 2018. All patients with a diagnosis of nonsyndromic isolated sagittal craniosynostosis were included and classified into one of 4 groups by the type of surgical correction performed (H-type, FLAG, endoscopic, other). The authors identified 166 consecutive patients with a mean age at time of surgery of 6.7 ± 4.0 months. 91 (54.8%) carried a diagnosis of nonsyndromic sagittal synostosis. 63 patients underwent H-type procedures, 9 underwent FLAG procedures, 5 underwent endoscopic procedures, and 14 were classified as other (distraction or other implant). Perioperatively, the FLAG group had the shortest ICU stay (1.3 days, P < 0.05), postoperative transfusion requirement (42cc pRBC, P < 0.001), and complication rate (0.0%). The endoscopic group had the shortest surgical time at 2.00 hours (p < 0.001). No statistically significant difference in cranial index or revision procedures between the four groups was identified. Overall, the mean length of follow-up was 25.3 months. All procedures had similar results for cranial index with decreased surgical time, transfusion volume, and hospital stay seen in FLAG and endoscopic groups.

How to bargain successfully with adolescents: What can be learned from youth development professionals.

This study examines risks and potential benefits that youth professionals experience in bargaining with adolescents. We conducted semistructured qualitative interviews with 50 experienced adult leaders of 27 high-quality arts, technology, and leadership youth programs (serving ethnically-diverse teens). Half worked with younger teens (ages 11-14), half with older (ages 14-18). Leaders reported bargaining in ways responsive to youth's wants and needs, reaching win-win agreements. Leaders of younger youth experienced more risks in bargaining, so took greater control over what was bargained. They used bargains most often to motivate when youth's enthusiasm dropped, and these bargains sometimes helped youth develop self-motivation. Leaders of older youth reported fewer risks and more benefits. They bargained as equals, asking youth to share decision-making responsibility. They used bargaining as a pedagogical tool to model, support, and challenge youth, which helped build their capacities for deliberative decision-making. The findings illuminate strategies for practitioners to use bargaining effectively.

Temporal population variability in local forest communities has mixed effects on tree species richness across a latitudinal gradient.

Among the local processes that determine species diversity in ecological communities, fluctuation-dependent mechanisms that are mediated by temporal variability in the abundances of species populations have received significant attention. Higher temporal variability in the abundances of species populations can increase the strength of temporal niche partitioning but can also increase the risk of species extinctions, such that the net effect on species coexistence is not clear. We quantified this temporal population variability for tree species in 21 large forest plots and found much greater variability for higher latitude plots with fewer tree species. A fitted mechanistic model showed that among the forest plots, the net effect of temporal population variability on tree species coexistence was usually negative, but sometimes positive or negligible. Therefore, our results suggest that temporal variability in the abundances of species populations has no clear negative or positive contribution to the latitudinal gradient in tree species richness.

Expression of ion transport genes in ionocytes isolated from larval zebrafish (Danio rerio) exposed to acidic or Na+-deficient water.

In zebrafish (Danio rerio), a specific ionocyte subtype, the H+-ATPase-rich (HR) cell, is presumed to be a significant site of transepithelial Na+ uptake/acid secretion. During acclimation to environments differing in ionic composition or pH, ionic and acid-base regulations are achieved by adjustments to the activity level of HR cell ion transport proteins. In previous studies, the quantitative assessment of mRNA levels for genes involved in ionic and acid-base regulations relied on measurements using homogenates derived from the whole body (larvae) or the gill (adult). Such studies cannot distinguish whether any differences in gene expression arise from adjustments of ionocyte subtype numbers or transcriptional regulation specifically within individual ionocytes. The goal of the present study was to use fluorescence-activated cell sorting to separate the HR cells from other cellular subpopulations to facilitate the measurement of gene expression of HR cell-specific transporters and enzymes from larvae exposed to low pH (pH 4.0) or low Na+ (5 µM) conditions. The data demonstrate that treatment of larvae with acidic water for 4 days postfertilization caused cell-specific increases in H+-ATPase (atp6v1aa), ca17a, ca15a, nhe3b, and rhcgb mRNA in addition to increases in mRNA linked to cell proliferation. In fish exposed to low Na+, expression of nhe3b and rhcgb was increased owing to HR cell-specific regulation and elevated numbers of HR cells. Thus, the results of this study demonstrate that acclimation to low pH or low Na+ environmental conditions is facilitated by HR cell-specific transcriptional control and by HR cell proliferation.

The role of TASK-2 channels in CO2 sensing in zebrafish (Danio rerio).

Peripheral chemosensitivity in fishes is thought to be mediated by serotonin-enriched neuroepithelial cells (NECs) that are localized to the gills of adults and the integument of larvae. In adult zebrafish (Danio rerio), branchial NECs are presumed to mediate the cardiorespiratory reflexes associated with hypoxia or hypercapnia, whereas in larvae, there is indirect evidence linking cutaneous NECs to hypoxic hyperventilation and hypercapnic tachycardia. No study yet has examined the ventilatory response of larval zebrafish to hypercapnia, and regardless of developmental stage, the signaling pathways involved in CO2 sensing remain unclear. In the mouse, a background potassium channel (TASK-2) contributes to the sensitivity of chemoreceptor cells to CO2. Zebrafish possess two TASK-2 channel paralogs, TASK-2 and TASK-2b, encoded by kcnk5a and kcnk5b, respectively. The present study aimed to determine whether TASK-2 channels are expressed in NECs of larval zebrafish and whether they are involved in CO2 sensing. Using immunohistochemical approaches, TASK-2 protein was observed on the surface of NECs in larvae. Exposure of larvae to hypercapnia caused cardiac and breathing frequencies to increase, and these responses were blunted in fish experiencing TASK-2 and/or TASK-2b knockdown. The results of these experiments suggest that TASK-2 channels are involved in CO2 sensing by NECs and contribute to the initiation of reflex cardiorespiratory responses during exposure of larvae to hypercapnia.

Assessing intracellular pH regulation in H+-ATPase-rich ionocytes in zebrafish larvae using in vivo ratiometric imaging.

The H+-ATPase-rich (HR) cells of zebrafish larvae are a sub-type of ion-transporting cell located on the yolk sac epithelium that are responsible for Na+ uptake and H+ extrusion. Current models of HR cell ion transport mechanisms in zebrafish larvae are well established, but little is known about the involvement of the various ion transport pathways in regulating intracellular acid-base status. Here, a ratiometric imaging technique was developed and validated to monitor intracellular pH (pHi) continuously in larval zebrafish HR cells in vivo Gene knockdown or CRISPR/Cas9 knockout approaches were used to evaluate the roles of the two principal apical membrane acid excretory pathways, the Na+/H+ exchanger (NHE3b; slc9a3.2) and the H+-ATPase (atpv1aa). Additionally, the role of HR cell cytosolic carbonic anhydrase (CAc) was investigated because of its presumed role in providing H+ for Na+/H+ exchange and H+-ATPase. The temporal pattern and extent of intracellular acidification during exposure of fish to 1% CO2 and the extent of post-CO2 alkalisation were altered markedly in fish experiencing knockdown/knockout of CAc, NHE3b or H+-ATPase. Although there were slight differences among the three knockdown/knockout experiments, the typical response was a greater degree of intracellular acidification during CO2 exposure and a reduced capacity to restore pHi to baseline levels post-hypercapnia. The metabolic alkalosis and subsequent acidification associated with 20 mmol l-1 NH4Cl exposure and its washout were largely unaffected by gene knockdown. Overall, the results suggest markedly different mechanisms of intracellular acid-base regulation in zebrafish HR cells depending on the nature of the acid-base disturbance.

Modeling lateral plume deflection in the wake of an elongated building.

The plume dispersion model AERMOD provides an efficient method for modeling ground-level pollutant concentrations in wakes of buildings. In recent years, several studies have shown that the downwash algorithms within AERMOD often perform poorly in certain applications. Some studies have proposed modifications to the downwash algorithm in AERMOD to bring the model closer to representing the underlying physical processes associated with building downwash and closer to more accurately modeling observed pollutant concentrations. One such study by Monbureau et al. (2018) made changes to the model that significantly improved its ability to model ground level concentrations for a simple case of a single rectangular building with an elevated, effluent-emitting stack experiencing winds perpendicular to the upwind side of the building. The present study introduces a simple algorithm to enhance AERMOD's ability to appropriately match the dispersion pattern in the complex flow case of non-orthogonal winds. This algorithm, which is based on a rich set of Large-Eddy Simulations (LES), applies to a variety of building dimensions, stack locations, and stack heights. A sensitivity analysis demonstrates how additional modifications to the downwash algorithm may further improve AERMOD in modeling the spatial location of observed ground-level effluent.

Awake vs. asleep motor mapping for glioma resection: a systematic review and meta-analysis.

BACKGROUND: Intraoperative stimulation (IS) mapping has become the preferred standard treatment for eloquent tumors as it permits a more accurate identification of functional areas, allowing surgeons to achieve higher extents of resection (EOR) and decrease postoperative morbidity. For lesions adjacent to the perirolandic area and descending motor tracts, mapping can be done with both awake craniotomy (AC) and under general anesthesia (GA). OBJECTIVE: We aimed to determine which anesthetic protocol-AC vs. GA-provides better patient outcomes by comparing EOR and postoperative morbidity for surgeries using IS mapping in gliomas located near or in motor areas of the brain. METHODS: A systematic literature search was carried out to identify relevant studies from 1983 to 2019. Seven databases were screened. A total of 2351 glioma patients from 17 studies were analyzed. RESULTS: A random-effects meta-analysis revealed a trend towards a higher mean EOR in AC [90.1% (95% C.I. 85.8-93.8)] than with GA [81.7% (95% C.I. 72.4-89.7)] (p = 0.06). Neurological deficits were divided by timing and severity for analysis. There was no significant difference in early neurological deficits [20.9% (95% C.I. 4.1-45.0) vs. 25.4% (95% C.I. 13.6-39.2)] (p = 0.74), late neurological deficits [17.1% (95% C.I. 0.0-50.0) vs. 3.8% (95% C.I. 1.1-7.6)] (p = 0.06), or in non-severe [28.4% (95% C.I. 0.0-88.5) vs. 20.1% (95% C.I. 7.1-32.2)] (p = 0.72), and severe morbidity [2.6% (95% C.I. 0.0-15.5) vs. 4.5% (95% C.I. 1.1-9.6)] (p = 0.89) between patients who underwent AC versus GA, respectively. CONCLUSION: Mapping during resection of gliomas located in or near the perirolandic area and descending motor tracts can be safely carried out with both AC and GA.

Three-Dimensional-Printed Temporal Mandibular Joint for Use in Mandibular Distraction for Patients With Craniofacial Microsomia.

The objective of this study is to validate the proof of concept of a 3-dimensional (3D)-printed temporal mandibular joint (TMJ) for use in mandibular distraction in patients with severe craniofacial microsomia (CFM). Patients with Pruzansky-Kaban IIB and III have severe condylar dysplasia and abnormal or absent TMJs, often resulting in upper airway obstruction during infancy. As these patients progress, they require subsequent surgeries to correct facial asymmetry and TMJ function. While studies have shown promising outcomes with costochondral grafting or mandibular distraction without a TMJ in the setting of patients with Pruzansky-Kaban IIB and III it is often unsuccessful in avoiding tracheostomy during infancy. Using an adult head and neck cadaver, the right condylar head was removed to emulate a Pruzansky-Kaban III mandible. A 3D model of an adult skull was obtained. The 3D TMJ was replaced into the cadaver and KLS distractor applied in the vertical orientation. The authors achieved adequate distraction using a 3D-printed TMJ. The 3D structure developed here can potentially be used for clinical application in CFM patients with absent or rudimentary TMJ for distraction and further avoidance of the need for tracheostomy for airway obstruction.

Child and Caregiver Perspectives Towards Facial Appearance in Children With Microtia With or Without Craniofacial Microsomia Using a Newly Developed Likert Scale.

Craniofacial microsomia (CFM) is the second most common congenital craniofacial malformation characterized by asymmetric malformation of the ear and mandible. Numerous studies have reported the importance of child perspective and psychosocial issues in patients with craniofacial abnormalities. However, clinical tools to evaluate child and caregiver perspectives in patients with microtia with or without CFM have been limited or not reported in the literature. The authors aimed to (1) To develop a tool for measuring patient and caregiver evaluation of facial appearance as it relates to microtia and craniofacial microsomia (CFM). (2) To utilize this tool in comparing children, between 7 and 20 years of age, and caregiver perspectives towards facial appearance in patients with microtia with or without craniofacial microsomia (CFM). A prospective single center study conducted from 2016 to 2017 using newly developed 13-item (Microtia) and 27-item (CFM) 5-point Likert scale Likert scale questionnaires given to patients with CFM and caregivers at a craniofacial center. Aged 7 to 20 (N = 25) and their caregivers. A total of 25 patients (13 male, 12 female; mean age at time of survey 13.2 ±â€Š3.7) met criteria for the study. The Likert scale developed and presented in this study may be a useful tool for clinical use in investigating patient and caregiver perspectives for planning surgical timeline. Based on our pilot data it is important to incorporate all voices into decision-making on timing.

Redefining physiological responses of moose (Alces alces) to warm environmental conditions.

We tested the concept that moose (Alces alces) begin to show signs of thermal stress at ambient air temperatures as low as 14 °C. We determined the response of Alaskan female moose to environmental conditions from May through September by measuring core body temperature, heart rate, respiration rate, rate of heat loss from exhaled air, skin temperature, and fecal and salivary glucocorticoids. Seasonal and daily patterns in moose body temperature did not passively follow the same patterns as environmental variables. We used large changes in body temperature (≥1.25 °C in 24hr) to indicate days of physiological tolerance to thermal stressors. Thermal tolerance correlated with high ambient air temperatures from the prior day and with seasonal peaks in solar radiation (June), ambient air temperature and vapor pressure (July). At midday (12:00hr), moose exhibited daily minima of body temperature, heart rate and skin temperature (difference between the ear artery and pinna) that coincided with daily maxima in respiration rate and the rate of heat lost through respiration. Salivary cortisol measured in moose during the morning was positively related to the change in air temperature during the hour prior to sample collection, while fecal glucocorticoid levels increased with increasing solar radiation during the prior day. Our results suggest that free-ranging moose do not have a static threshold of ambient air temperature at which they become heat stressed during the warm season. In early summer, body temperature of moose is influenced by the interaction of ambient temperature during the prior day with the seasonal peak of solar radiation. In late summer, moose body temperature is influenced by the interaction between ambient temperature and vapor pressure. Thermal tolerance of moose depends on the intensity and duration of daily weather parameters and the ability of the animal to use physiological and behavioral responses to dissipate heat loads.

Inherited anxiety-related parent-infant dyads alter LHPA activity.

The pathogenesis of post-traumatic stress disorder (PTSD) is incompletely understood. We hypothesize that disruptions in mother-child relations may be a key contributor to development of PTSD. A normal and healthy separation-individuation process requires adaptations of self- and interactive contingency in both the mother and her child, especially in early childhood development. Anxious mothers are prone to overprotection, which may hinder the individuation process in their children. We examined long-term stress hormones and other stress markers in subjects three generations removed from the Holocaust, to assess the long-term consequences of inherited behavioral and physiological responses to prior stress and trauma. Jewish subjects who recalled overprotective parental behavior had higher hairsteroid-concentrations and dampened limbic-hypothalamic-pituitary-adrenal (LHPA) axis reactivity compared to German and Russian-German subjects with overprotective parents. We suggest that altered LHPA axis activity in maternally overprotected Jewish subjects may indicate a transmitted pathomechanism of "frustrated individuation" resulting from cross-generational anti-Semitic experiences. Thus measurements of hairsteroid-concentrations and parenting practices may have clinical value for diagnosis of PTSD. We propose that this apparent inherited adaptivity of LHPA axis activity could promote higher individual stress resistance, albeit with risk of an allostatic overload.