Psychosocial Resources Predicting Maternal and Paternal Positive Parenting and Lower Child Abuse Risk.

Young children have the highest victimization rates of physical abuse in their first year of life, making up nearly half of all child abuse-related fatalities. More effective prevention is needed to reduce child victimization, yet many risk reduction models rely on problematic inclusion criteria, only intervene after maltreatment has occurred, or focus only on mothers. More proactive prevention models that promote positive parenting practices early in the transition to parenthood could be key to reducing child maltreatment. The current study sought to assess how both mothers' and fathers' psychosocial resources (e.g., emotion regulation, coping, and social support) and empathy can predict positive parenting and predict lower child abuse risk across time in a cross-lagged model. Parenting and abuse risk were examined prenatally, through the transition into parenthood, until children were 4 years old. First time mothers and their partners were recruited in the third trimester of pregnancy and assessed again when children were 6 months, 18 months, and 4 years old. Separate path models for mothers and fathers analyzed whether psychosocial resources and empathy at earlier timepoints predicted their positive parenting and lower abuse risk by the time children were age 4. Findings demonstrated that mothers' earlier empathy predicted later positive parenting and earlier positive parenting predicted later empathy. Fathers' lower prenatal abuse risk predicted greater subsequent empathy. Both mothers' and fathers' psychosocial resources and empathy at earlier timepoints predicted later positive parenting. Parents' psychosocial resources can be integral assets in positive, effective parenting approaches both concurrently and longitudinally. Mothers' and fathers' resources are an important point of intervention prior to and during the transition into parenthood to support healthier families that would confer benefits to child functioning.

Riociguat in pulmonary hypertension and heart failure with preserved ejection fraction: the haemoDYNAMIC trial.

AIMS: The presence of pulmonary hypertension (PH) severely aggravates the clinical course of heart failure with preserved ejection fraction (HFpEF). To date, neither established heart failure therapies nor pulmonary vasodilators proved beneficial. This study investigated the efficacy of chronic treatment with the oral soluble guanylate cyclase stimulator riociguat in patients with PH-HFpEF. METHODS AND RESULTS: The phase IIb, randomized, double-blind, placebo-controlled, parallel-group, multicentre DYNAMIC trial assessed riociguat in PH-HFpEF. Patients were recruited at five hospitals across Austria and Germany. Key eligibility criteria were mean pulmonary artery pressure ≥25 mmHg, pulmonary arterial wedge pressure >15 mmHg, and left ventricular ejection fraction ≥50%. Patients were randomized to oral treatment with riociguat or placebo (1:1). Patients started at 0.5 mg three times daily (TID) and were up-titrated to 1.5 mg TID. The primary efficacy endpoint was change from baseline to week 26 in cardiac output (CO) at rest, measured by right heart catheterization. Primary efficacy analyses were performed on the full analysis set. Fifty-eight patients received riociguat and 56 patients placebo. After 26 weeks, CO increased by 0.37 ± 1.263 L/min in the riociguat group and decreased by -0.11 ± 0.921 L/min in the placebo group (least-squares mean difference: 0.54 L/min, 95% confidence interval 0.112, 0.971; P = 0.0142). Five patients dropped out due to riociguat-related adverse events but no riociguat-related serious adverse event or death occurred. CONCLUSION: The vasodilator riociguat improved haemodynamics in PH-HFpEF. Riociguat was safe in most patients but led to more dropouts as compared to placebo and did not change clinical symptoms within the study period.

Reliability and Validity of the Lower Extremity Motor Activity Log for Measuring Real-World Leg Use in Adults With Multiple Sclerosis.

OBJECTIVES: To determine the test-retest reliability and validity of the Lower Extremity Motor Activity Log (LE-MAL) for assessing LE use in the community in adults with multiple sclerosis (MS). DESIGN: Prospective analysis of measures conducted by trained examiners. SETTING: Participants were evaluated by telephone on several measures of LE use. PARTICIPANTS: Adults with MS (N=43). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The LE-MAL has 3 subscales (Assistance, Functional Performance, and Confidence). It was administered twice, at least 2 weeks apart. The Multiple Sclerosis Walking Scale (MSWS-12), Patient Determined Disease Steps (PDDS), and Mobility Scale were only administered during the first call. RESULTS: The test-retest reliability of the composite and the 3 subscale LE-MAL scores were high (intraclass correlation, >0.94). The composite and subscale LE-MAL scores were strongly correlated with the MSWS-12, PDDS, and Mobility Scale scores (r=-0.56 to -0.77; P<.001). CONCLUSION: This initial study suggests that the LE-MAL reliably and validly measures LE use in the community in adults with MS.

Accuracy and Interobserver Reliability of Magnetic Resonance Imaging for Placenta Accreta Spectrum Disorders.

OBJECTIVE: This study aims to define the accuracy, predictive value, and interobserver reliability of magnetic resonance imaging (MRI) in the diagnosis of placenta accreta spectrum (PAS) disorders. STUDY DESIGN: Two experienced radiologists independently interpreted the MRI studies of patients with possible PAS from two referral centers. Radiologists were blinded to sonographic and clinical information. We calculated diagnostic testing characteristics and kappa statistics of interobserver reliability for MRI findings of PAS. RESULTS: Sixty-eight MRI cases were evaluated. Confirmed PAS and severe PAS were present in 44 (65%) and 20 (29%) cases. For the diagnosis of any PAS, MRI had a sensitivity 66%, specificity 71%, positive predictive value (PPV) 81%, negative predictive value (NPV) 53%, and accuracy 68%. For the diagnosis of severe PAS (percreta), MRI had a sensitivity 85%, specificity 79%, PPV 63%, NPV 93%, and accuracy 81%. The accuracy of individual signs of PAS was lower (44-65%). Interobserver agreement was almost perfect for previa; substantial for myometrial interruptions, PAS, severe PAS, and placental bulging/balling; and moderate to slight for other signs of PAS. CONCLUSION: Although the interobserver reliability of MRI for a diagnosis of PAS is substantial, the accuracy and predictive value are modest and lower than previously reported.

Bidirectional Spillover in the Family across the Transition to Parenthood.

Although family systems theory posits reciprocal causality between subsystems of the family, such as intimate partner violence exacerbating harsh parenting and vice versa, longitudinal studies with cross-lagged models have been used infrequently to test these principles. As guided by the spillover model, this study examined bidirectional associations between couple dysfunction, parent-child aggression risk, and child functioning across the transition to parenthood to determine whether and how disruptions in one subsystem relate to problems in other family subsystems. Participants were 201 first-time mothers and 151 fathers from a diverse community sample, evaluated during pregnancy, and reassessed two more times through their child's first 18 months of life. Individual and dyadic path model results indicate bidirectional spillover effects between parent-child aggression risk and child functioning for both mothers and fathers, and spillover from parent-child aggression risk to couple dysfunction for mothers but not fathers. However, limited spillover effects were identified between couple functioning and child adjustment, in contrast to previous work. Findings suggest that spillover can happen reciprocally and early in the family, supporting transactional models of behavior and highlighting the need for early family level intervention.

Aunque la teoría de sistemas familiares plantea una causalidad recíproca entre los subsistemas de la familia, como la violencia de pareja que exacerba la crianza hostil y viceversa, se han utilizado ocasionalmente estudios longitudinales con modelos de referencias cruzadas para evaluar estos principios. Guiado por el modelo de transferencia, este estudio analizó las asociaciones bidireccionales entre la disfunción de la pareja, el riesgo de agresión entre padres e hijos y el funcionamiento de los niños durante la transición a la paternidad a fin de determinar si y cómo las alteraciones de un subsistema se relacionan con los problemas en otros subsistemas familiares. Los participantes fueron 201 madres primerizas y 151 padres de una muestra comunitaria diversa evaluada durante el embarazo y reevaluada dos veces más a lo largo de los primeros 18 meses de vida de su hijo. Los resultados del modelo de ruta individual y diádico indican efectos de transferencia bidireccional entre el riesgo de agresión entre padres e hijos y el funcionamiento de los niños tanto para las madres como para los padres, y transferencia del riesgo de agresión entre padres e hijos a la disfunción de la pareja para las madres pero no para los padres. Sin embargo, se identificaron efectos escasos de transferencia entre el funcionamiento de la pareja y la adaptación de los niños en comparación con trabajos anteriores. Los resultados sugieren que la transferencia puede ocurrir recíprocamente y pronto en la familia, lo cual respalda modelos transaccionales de comportamiento y destaca la necesidad de una intervención temprana a nivel familiar.

Allopatry, hybridization, and reproductive isolation in Arctostaphylos.

PREMISE: Hybridization plays a key role in introgressive adaptation, speciation, and adaptive radiation as a source of evolutionary innovation. Hybridization is considered common in Arctostaphylos, yet species boundaries are retained in stands containing multiple species. Arctostaphylos contains diploids and tetraploids, and recent phylogenies indicate two clades; we hypothesize combinations of these traits limit or promote hybridization rates. METHODS: We statistically analyzed co-occurrence patterns of species by clade membership and ploidy level from 87 random 0.1 ha plots. We sampled multiple sites to analyze for percent hybridization based on morphology. Finally, phenophases were analyzed by scoring herbarium sheets for a large number of taxa from both clades as well as tetraploids, and second, surveying three field sites over two years for divergence in phenological stages between co-occurring taxa. RESULTS: Most taxa in Arctostaphylos are allopatric relative to other congenerics. When two taxa co-occur, the patterns are a diploid with a tetraploid, or two diploids from different clades. When three taxa co-occur, the pattern is two diploids from different clades and a tetraploid. Field and herbarium data both indicate flowering phenology is displaced between diploids from the two clades; one of the diploid clades and tetraploids overlap considerably. CONCLUSIONS: The two deep clades in Arctostaphylos are genetically distant, with hybrids rare or non-existent when taxa co-occur. Reproductive isolation between clades is enhanced by displaced flowering phenology for co-occurring species. Within clades, taxa appear to have few reproductive barriers other than an allopatric distribution or different ploidy levels.

Neonatal Outcomes Associated with Umbilical Cord Milking in Preterm Multiple Gestations.

OBJECTIVE: Our aim was to evaluate the effect of umbilical cord milking on outcomes for preterm multiples. STUDY DESIGN: We implemented a policy of cord milking in neonates born at less than 30 weeks' gestation in September 2011. We compared cord milking in multiples with a historical cohort. Multivariable logistic regression models estimated the effect of cord milking on a composite neonatal adverse outcome. Secondary outcomes were hematocrit at birth, need for blood transfusion, and inotrope use. RESULTS: We identified 149 neonates (120 twins, 29 triplets), 51 historical controls, and 98 neonates with cord milking. Cord milking was associated with a lower rate of adverse composite neonatal outcome in univariable analysis (odds ratio [OR]: 0.36; 95% confidence interval [CI]: 0.15-0.84). However, in multivariable modeling, the effect was not significant (adjusted OR [aOR]: 0.54, 95% CI: 0.23-1.28). Hematocrit was 4.6 unit % (95% CI: 2-7.3) higher in the cord milking group, and cord milking was associated with a lower rate of blood transfusion (aOR: 0.28; 95% CI: 0.1-0.74; p = 0.01). There was no difference in inotrope administration. CONCLUSION: Umbilical cord milking was not associated with a decrease in composite neonatal adverse outcome. However, we observed an increase in hematocrit and decreased need for blood transfusion in neonates with cord milking.

Cognitive-Affective Pathways to Child Depressive and Anxious Symptoms: Role of Children's Discipline Attributions.

Children's maladaptive cognitive attributions may elicit affective reactions that contribute to depressive and anxious symptoms. This study investigated cognitive-affective pathways in depressive and anxious symptoms in a sample of 110 prepubertal children, evaluating children's specific appraisals of experiences of parental discipline as well as general attributional style, along with their hopelessness, self-esteem, and shame. Pathways toward depressive and anxious symptoms were tested simultaneously to identify potential unique etiological mechanisms. Results suggested that lower self-esteem strongly contributed to depressive and anxious symptoms, whereas shame related to depression only and hopelessness related to depression only marginally. Additionally, general negative attributional style and low sense of control over discipline related to all three affective elements. Lastly, low sense of discipline control directly predicted depressive symptoms, whereas beliefs that discipline was undeserved directly predicted anxious symptoms. Future work should continue to examine the role of children's discipline-specific attributions, which appear important in internalizing symptoms.

Predicting Child Problem Behavior and Maternal/Paternal Parent-Child Aggression: Identifying Early Prevention Targets.

Parental socio-cognitive factors may predict their physical discipline use as well as their perceptions of children's problem behavior; infant temperament may also influence parents' discipline use. Using a bidirectional approach, the current study investigated whether attitudes approving of parent-child aggression (PCA), negative child behavior attributions, knowledge of nonphysical discipline options, and infant temperament predicted 186 mothers' and 146 fathers' PCA use and child problem behaviors one year later. Findings indicated mothers who approved of PCA use and held negative child attributions were more likely to report greater subsequent PCA use; less knowledge of nonphysical discipline options predicted more perceived problem behaviors one year later. Fathers were more likely to engage in PCA with toddlers if they had less knowledge of nonphysical discipline options but also if they viewed their infants as active. Contributors to mothers' and fathers' PCA use and implications for prevention efforts and children's outcomes are considered.

Magnetic resonance imaging is often misleading when used as an adjunct to ultrasound in the management of placenta accreta spectrum disorders.

BACKGROUND: Magnetic resonance imaging is reported to have good sensitivity and specificity in the diagnosis of placenta accreta spectrum disorders, and is often used as an adjunct to ultrasound. But the additional utility of obtaining magnetic resonance imaging to assist in the clinical management of patients with placenta accreta spectrum disorders, above and beyond the information provided by ultrasound, is unknown. OBJECTIVE: We aimed to determine whether magnetic resonance imaging provides data that may inform clinical management by changing the sonographic diagnosis of placenta accreta spectrum disorders. STUDY DESIGN: In all, 78 patients with sonographic evidence or clinical suspicion of placenta accreta spectrum underwent magnetic resonance imaging of the abdomen and pelvis in orthogonal planes through the uterus utilizing T1- and T2-weighted imaging sequences at the University of Utah and the University of Colorado from 1997 through 2017. The magnetic resonance imaging was interpreted by radiologists with expertise in diagnosis of placenta accreta spectrum who had knowledge of the sonographic interpretation and clinical risk factors for placenta accreta spectrum disorders. The primary outcome was a change in diagnosis from sonographic interpretation that could alter clinical management, which was defined a priori. Diagnostic accuracy was verified by surgical and histopathologic diagnosis at the time of delivery. RESULTS: A change in diagnosis that could potentially alter clinical management occurred in 28 (36%) cases. Magnetic resonance imaging correctly changed the diagnosis in 15 (19%), and correctly confirmed the diagnosis in 34 (44%), but resulted in an incorrect change in diagnosis in 13 (17%), and an incorrect confirmation of ultrasound diagnosis in 15 (21%). Magnetic resonance imaging was not more likely to change a diagnosis in the 24 cases of posterior and lateral placental location compared to anterior location (33% vs 37%, P = .84). Magnetic resonance imaging resulted in overdiagnosis in 23% and in underdiagnosis in 14% of all cases. When ultrasound suspected severe disease (percreta) in 14 cases, magnetic resonance imaging changed the diagnosis in only 2 cases. Lastly, the proportion of accurate diagnosis with magnetic resonance imaging did not improve over time (61-65%, P = .96 for trend) despite increasing volume and increasing numbers of changed diagnoses. CONCLUSION: Magnetic resonance imaging resulted in a change in diagnosis that could alter clinical management of placenta accreta spectrum disorders in more than one third of cases, but when changed, the diagnosis was often incorrect. Given its high cost and limited clinical value, magnetic resonance imaging should not be used routinely as an adjunct to ultrasound in the diagnosis of placenta accreta spectrum until evidence for utility is clearly demonstrated by more definitive prospective studies.

Epidural Fat and Its Association with Pain, Physical Function, and Disability Among Older Adults with Low Back Pain and Controls.

Objective: To examine epidural fat and its relationship to pain, physical function, and disability among older adults with chronic low back pain, chronic low back pain plus leg pain, and controls. Design: Cross-sectional, comparative study. Setting: Standardized examinations were conducted in a research laboratory, and magnetic resonance images were obtained. Subjects: A total of 93 adults age 60 to 85 years (24 with chronic back pain, 25 with chronic back pain plus leg pain, and 44 controls). Methods: Reliability for assessment of epidural fat diameter, averaged across spinal levels, was established (intraclass correlation coefficient = 0.95). Linear regression was used to explore how epidural fat diameter related to self-reported (Short Form-36 Health Survey: physical component summary score) and performance-based (stair climb performance) measures of physical function among adults with chronic back pain with and without leg pain, as compared with controls, while controlling for age, sex, and body mass index. Associations between epidural fat and pain intensity and low back pain-related disability were also explored (P ≤ 0.050). Results: Epidural fat helped explain self-reported function (P < 0.001); adults with axial low back pain (LBP) may have a relationship between epidural fat and self-report function that is different from controls (P = 0.015). Relationships between epidural fat and stair performance were significantly different from controls for those with LBP (P = 0.000) but not for those with LBP plus leg pain (P = 0.366). Relationships between epidural fat and pain intensity and/or disability were not found. Conclusions: Increased epidural fat may help explain better function among older adults with chronic axial back pain, but not among those who also report leg pain.

Novel Modality for Neck Rejuvenation: A Prospective Multicenter Trial of Percutaneous Radiofrequency Ablation of the Cervical Branch of the Facial Nerve.

BACKGROUND: Neck rejuvenation offers few modalities of treatments limited to either invasive plastic surgery or temporary neuromodulation using botulinum toxin. OBJECTIVE: To access the efficacy, longevity, and safety of percutaneous monopolar radiofrequency (RF) ablation of the cervical branch of the facial nerve innervating the platysma for neck rejuvenation. MATERIALS AND METHODS: This prospective, multicenter trial enrolled 19 adult patients with noticeable platysmal banding at 2 different centers. All patients underwent RF ablation on the cervical branch of the facial nerve. Response was assessed immediately after treatment and then at 1, 4, 12, and 24 weeks after the procedure using photography. Masked investigators compared baseline photography and follow-up intervals to evaluate the results. RESULTS: Seventeen of the 18 patients had improvement in the platysmal banding. One patient was disqualified after ablation. Long-term sequalae such as scarring, burns, ulceration, hypopigmentation, or hyperpigmentation were not reported. CONCLUSION: The results of this multicenter study support that RF ablation of the cervical branch of the facial nerve is a novel technique that results in improvement of platysmal banding. This technique is an emerging alternative, nonsurgical option for neck rejuvenation that is relatively safe, with little downtime for the patient.

Polymorphisms of the Toll-Like Receptor 2 of Goats (Capra hircus) may be Associated with Somatic Cell Count in Milk.

Toll-like receptor 2 (TLR2) plays an important role in recognition by the innate immune system of Gram-positive bacteria. As Gram-positive bacteria cause mastitis, we examined variations in the region of the TLR2 gene that codes for the extracellular domain. Samples of forty goats from a single dairy herd were collected, half with low SCC (≤200,000 cells/mL), and half with higher SCC. Two synonymous single nucleotide polymorphisms (SNPs) were identified: 840G > A and 1083A > G. One nonsynonymous SNP 739G > A was identified. This coded for valine or isoleucine, which have similar physiochemical properties, and was not in a region coding for a known functional domain. Surprisingly, the least square mean SCC of the heterozygous goats (146,220) was significantly lower than the SCC of homozygous GG goats (537,700; p = 0.004), although these two groups were similar in days in milk (p = 0.984), and there was no significant difference by breed (p = 0.941). Because factors other than mastitis can affect SCC and our sample sizes were limited, additional studies are needed to corroborate an association between TLR2 genotype and SCC or mastitis in goats.

Koalas (Phascolarctos cinereus) From Queensland Are Genetically Distinct From 2 Populations in Victoria.

The koala (Phascolarctos cinereus) suffered population declines and local extirpation due to hunting in the early 20th century, especially in southern Australia. Koalas were subsequently reintroduced to the Brisbane Ranges (BR) and Stony Rises (SR) by translocating individuals from a population on French Island descended from a small number of founders. To examine genetic diversity and north-south differentiation, we genotyped 13 microsatellite markers in 46 wild koalas from the BR and SR, and 27 Queensland koalas kept at the US zoos. The Queensland koalas displayed much higher heterozygosity (H O = 0.73) than the 2 southern Australian koala populations examined: H O = 0.49 in the BR, whereas H O = 0.41 in the SR. This is consistent with the historical accounts of bottlenecks and founder events affecting the southern populations and contrasts with reports of high genetic diversity in some southern populations. The 2 southern Australian koala populations were genetically similar (F ST = 0.018, P = 0.052). By contrast, northern and southern Australian koalas were highly differentiated (F ST = 0.27, P < 0.001), thereby suggesting that geographic structuring should be considered in the conservation management of koalas. Sequencing of 648bp of the mtDNA control region in Queensland koalas found 8 distinct haplotypes, one of which had not been previously detected among koalas. Queensland koalas displayed high mitochondrial haplotype diversity (H = 0.753) and nucleotide diversity (π = 0.0072), indicating along with the microsatellite data that North American zoos have maintained high levels of genetic diversity among their Queensland koalas.

Effect of umbilical cord milking on morbidity and survival in extremely low gestational age neonates.

OBJECTIVE: Delayed umbilical cord clamping benefits extremely low gestational age neonates (ELGANs) but has not gained wide acceptance. We hypothesized that milking the umbilical cord (MUC) would avoid resuscitation delay but improve hemodynamic stability and reduce rates for composite outcome of severe intraventricular hemorrhage, necrotizing enterocolitis, and/or death before discharge. STUDY DESIGN: We implemented a joint neonatal/maternal-fetal quality improvement process for MUC starting September 2011. The MUC protocol specified that infants who were born at <30 weeks of gestation undergo MUC 3 times over a duration of <30 seconds at delivery. Obstetric and neonatal data were collected until discharge. We compared the MUC group to retrospective ELGAN cohort delivered at our center between January 2010 and August 2011. Analysis was intention-to-treat. RESULTS: We identified 318 ELGANs: 158 eligible for MUC and 160 retrospective control neonates. No adverse events were reported with cord milking. There was no difference in neonatal resuscitation, Apgar scores, or admission temperature. Hemodynamic stability was improved in the MUC group with higher mean blood pressures through 24 hours of age, despite less vasopressor use (18% vs 32%; P < .01). The initial hematocrit value was higher (50% vs 45%; P < .01), and red cell transfusions were fewer (57% vs 79%; P < .01) in MUC vs control infants. Presence of the composite outcome was significantly less in MUC vs the historic control infants (22% v 39%; odds ratio, 1.81; 95% confidence interval, 1.06-3.10). There were also reductions in intraventricular hemorrhage, necrotizing enterocolitis, and death before hospital discharge. CONCLUSION: MUC improves early hemodynamic stability and is associated with lower rates of serious morbidity and death among ELGANs.

Frustration influences impact of history and disciplinary attitudes on physical discipline decision making.

Although intergenerational patterns of punitive physical punishment garner considerable research attention, the mechanisms by which historical, cognitive, and contextual factors interplay to influence disciplinary responding remains poorly understood. Disciplinary attitudes have been shown to mediate the association between disciplinary history and disciplinary responding. The present study investigated whether frustration influences these mediation effects. Half of a sample of 330 undergraduates was randomly assigned to frustration induction. Structural equation modeling confirmed that, for participants in the frustration condition, the relation between disciplinary history and physical discipline decision-making was fully mediated by attitudes approving physical discipline. In contrast, for respondents in the no-frustration condition, the pathway from disciplinary history to discipline decision-making was only partially mediated by attitudes. Under conditions of frustration, attitudes may become a more central means by which personal disciplinary history is associated with disciplinary decision-making.

Investigating the gastrointestinal physiology of mature horses with and without a history of cribbing behavior in response to feeding a digestive support supplement.

Cribbing, a stereotypic oral behavior observed in horses, involves placing incisors on a fixed object, arching the neck, pulling against the object, and emitting an audible grunt. This behavior has been associated with gastrointestinal (GI) dysfunction and gastric ulceration. In this randomized crossover study, we investigated the impact of a GI support supplement (SPL) on the GI environment and physiology of four cribbing (CB) and four non-cribbing horses (NCB). Mature Quarter Horses, acclimated to individual stalls for 16 hours daily with paddock turnout in pairs for 8 hours per day, were randomly assigned to receive either the SPL or placebo for 21 days, followed by a 2-week washout period. Fecal and gastric samples were collected for pH determination and blood samples were analyzed for serum cortisol and gastrin levels. Endoscopic examinations assessed gastric ulcer severity, and cribbing frequency and bouts were recorded via video surveillance. Data were analyzed using a mixed-model ANOVA. Results showed no differences in fecal and gastric pH between cribbing statuses. However, an interaction between supplementation and cribbing status was observed for squamous mucosa ulcer scores (P=0.003). There were no differences in glandular mucosa ulcer scores, serum cortisol, serum gastrin, and crib-bite count between CB and NCB horses or between supplementation groups. Crib-bout duration did not differ with supplementation, but differences were found between periods (P<0.05) and hour ranges (P<0.001). Our findings suggest that the GI support supplement may not effectively address cribbing behavior or alter the GI environment in NCB or CB horses.

Neoadjuvant radioimmunotherapy in pancreatic cancer enhances effector T cell infiltration and shortens their distances to tumor cells.

Radiotherapy is hypothesized to have an immune-modulating effect on the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) to sensitize it to anti-PD-1 antibody (a-PD-1) treatment. We collected paired pre- and posttreatment specimens from a clinical trial evaluating combination treatment with GVAX vaccine, a-PD-1, and stereotactic body radiation (SBRT) following chemotherapy for locally advanced PDACs (LAPC). With resected PDACs following different neoadjuvant therapies as comparisons, effector cells in PDACs were found to skew toward a more exhausted status in LAPCs following chemotherapy. The combination of GVAX/a-PD-1/SBRT drives TME to favor antitumor immune response including increased densities of GZMB+CD8+ T cells, TH1, and TH17, which are associated with longer survival, however increases immunosuppressive M2-like tumor-associated macrophages (TAMs). Adding SBRT to GVAX/a-PD-1 shortens the distances from PD-1+CD8+ T cells to tumor cells and to PD-L1+ myeloid cells, which portends prolonged survival. These findings have guided the design of next radioimmunotherapy studies by targeting M2-like TAM in PDACs.