Reward Reinforcement Creates Enduring Facilitation of Goal-directed Behavior.

Stimulus-response habits benefit behavior by automatizing the selection of rewarding actions. However, this automaticity can come at the cost of reduced flexibility to adapt behavior when circumstances change. The goal-directed system is thought to counteract the habit system by providing the flexibility to pursue context-appropriate behaviors. The dichotomy between habitual action selection and flexible goal-directed behavior has recently been challenged by findings showing that rewards bias both action and goal selection. Here, we test whether reward reinforcement can give rise to habitual goal selection much as it gives rise to habitual action selection. We designed a rewarded, context-based perceptual discrimination task in which performance on one rule was reinforced. Using drift-diffusion models and psychometric analyses, we found that reward facilitates the initiation and execution of rules. Strikingly, we found that these biases persisted in a test phase in which rewards were no longer available. Although this facilitation is consistent with the habitual goal selection hypothesis, we did not find evidence that reward reinforcement reduced cognitive flexibility to implement alternative rules. Together, the findings suggest that reward creates a lasting impact on the selection and execution of goals but may not lead to the inflexibility characteristic of habits. Our findings demonstrate the role of the reward learning system in influencing how the goal-directed system selects and implements goals.

Ex vivo generation of regulatory T cells from liver transplant recipients using costimulation blockade.

The potential of adoptive cell therapy with regulatory T cells (Tregs) to promote transplant tolerance is under active exploration. However, the impact of specific transplant settings and protocols on Treg manufacturing is not well-delineated. Here, we compared the use of peripheral blood mononuclear cells (PBMCs) from patients before or after liver transplantation to the use of healthy control PBMCs to determine their suitability for Treg manufacture using ex vivo costimulatory blockade with belatacept. Despite liver failure or immunosuppressive therapy, the capacity for Treg expansion during the manufacturing process was preserved. These experiments did not identify performance or quality issues that disqualified the use of posttransplant PBMCs-the currently favored protocol design. However, as Treg input correlated with output, significant CD4-lymphopenia in both pre- and posttransplant patients limited Treg yield. We therefore turned to leukapheresis posttransplant to improve absolute yield. To make deceased donor use feasible, we also developed protocols to substitute splenocytes for PBMCs as allostimulators. In addition to demonstrating that this Treg expansion strategy works in a liver transplant context, this preclinical study illustrates how characterizing cellular input populations and their performance can both inform and respond to clinical trial design and Treg manufacturing requirements.

Pinoxaden resistance in Lolium perenne L. is due to both target-site and non-target-site mechanisms.

Application of herbicides inhibiting acetyl CoA carboxylase (ACCase) has been one of the main strategies for selectively controlling grass weed species such as perennial ryegrass (Lolium perenne L.) in wheat and barley crops in New Zealand. In this study, we have confirmed and characterized resistance to pinoxaden, an ACCase-inhibiting herbicide, in a population of L. perenne. Dose-response experiments were conducted to assess the level of pinoxaden resistance, and based on the LD50 values, the studied population was 41.4-times more resistant to pinoxaden than a susceptible population. Application of malathion, an inhibitor of the cytochrome P450s, preceding pinoxaden treatment reduced the level of resistance to 9.7-fold. However, pre-treatment with the glutathione S-transferase (GST) inhibitor 4-chloro7- nitrobenzoxadiazole prior to pinoxaden treatment did not affect pinoxaden resistance. Partial sequencing of the ACCase gene revealed that the resistant population had an isoleucine to valine replacement at position 2041. These results suggest that both cytochrome P450-based and target-site mechanisms are jointly associated with this instance of pinoxaden resistance in L. perenne. The pinoxaden-resistant L. perenne individuals were also resistant to quizalofop-p-ethyl (108.6-fold), but they were susceptible to clethodim, which can, therefore, be used to manage this pinoxaden-resistant L. perenne. This is the first report of a L. perenne population in which a rare target-site mutation works in concert with enhanced cytochrome P-450 activity to confer pinoxaden resistance. Evolution of resistance to ACCase-inhibiting herbicides in this L. perenne population indicates that integrated weed management practices are required to prevent widespread resistance developing in New Zealand cereal crop systems.

Can Diagnostic Codes in Health Care Claims Data Identify Confirmed Chlamydial and Gonococcal Infections? A Retrospective Cohort Study, 2003 to 2017.

BACKGROUND: Because most sources of administrative claims data do not contain laboratory result data, researchers rely on diagnosis codes to identify cases of disease. The validity of using diagnosis codes to identify chlamydial and gonococcal infections in administrative claims data remains largely uninvestigated. METHODS: We conducted a retrospective cohort analysis using OptumLabs Data Warehouse, which includes deidentified medical (inpatient and outpatient) claims and laboratory test results. Among males and females aged 15 to 39 years during the period 2003-2017, we identified chlamydia and gonorrhea test results and corresponding diagnosis codes. Using test results as the criterion standard, we calculated the sensitivity and specificity of chlamydia and gonorrhea diagnosis codes to identify laboratory-confirmed infections. RESULTS: We identified 9.7 million chlamydia and gonorrhea test results among 3.1 million enrollees. Of the 176,241 positive chlamydia test results, only 11,515 had a corresponding diagnosis code, for a sensitivity of 6.5 (95% confidence interval [CI], 6.4-6.7) and a specificity of 99.5 (95% CI, 99.5-99.5). Corresponding diagnosis codes were identified for 8056 of the 31,766 positive gonorrhea test results, for a sensitivity of 25.4 (95% CI, 24.9-25.8) and a specificity of 99.7 (95% CI, 99.7-99.7). CONCLUSIONS: Our findings indicate that using only International Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification diagnosis codes to identify chlamydial and gonococcal infections substantially underestimates the burden of these diseases and inaccurately classifies laboratory-confirmed infections.

Paper towel test as independently self-administered to quantify cough-related urine loss: Compliance and comparisons with survey-only data in SWAN.

AIMS: The epidemiologic Study of Women's Health Across the Nation (SWAN) includes urinary incontinence (UI) questionnaire items. We introduced an independently self-administered paper towel test (PTT-ISA; invention disclosure #2021-347) to objectively demonstrate UI. Aims were to determine: (1) PTT-ISA compliance and (2) relationship to questionnaire results. METHODS: 276 community women were invited to complete both SWAN questionnaire and PTT-ISA. For PTT-ISA, a woman holds a trifold brown paper towel against her perineum while coughing hard three times. She checks the towel for wetness and compares it with pictorial showing wetted area gradations (dry towel through >6 ml/saturated). She then selects the best photo match for her towel. A newly conceptualized variable constructed as PTT-ISA plus questionnaire results was formed. RESULTS: Of 276 women, noncompliance with PTT-ISA was 2.2% (6 women). Four others (1.5%) were missing questionnaires. For the remaining 266 women, conceptual cohesiveness between questionnaire-only and PTT-ISA + questionnaire was demonstrated in 165 (62.0%). Lack of cohesiveness occurred in 101 (38.9%), including 41 women who said "no" to the questionnaire item indicative of stress UI and had leakage on PTT-ISA; leakage degree varied across the full pictorial spectrum from drops to saturated. CONCLUSION: PTT-ISA demonstrates high compliance, with rate comparable to survey compliance. It is a novel measure for objective sign of urine loss when independently self-administered by community women outside of a clinic environment. Further research comparing PTT-ISA with clinician-observed cough test is warranted. As independently self-administered, PTT-ISA is simple, noninvasive, inexpensive, and an acceptable test that adds value to otherwise survey-dependent research.

Low-Symmetry ß-Diketimine Aryloxide Rare-Earth Complexes: Flexible, Reactive, and Selective.

We report the synthesis, characterization, and reactivity of a new low-symmetry ß-diketimine featuring a pendant amino(methyl)phenol donor and its corresponding heteroleptic rare-earth (RE) complexes. This includes the first structurally characterized examples of alcoholysis and insertion from an isolated REIII amide in a ß-diketimine framework. The flexible methylene linkage leads to REIII complexes with tunable dynamic solution behavior that defines their stoichiometric and catalytic reactivity. The addition of a strong neutral donor ligand, tricyclohexylphosphine oxide, suppresses a prevalent catalyst degradation pathway (base-promoted elimination) and dramatically enhances the catalyst performance in the stereospecific ring-opening polymerization of rac-ß-butyrolactone. Our results further demonstrate the importance of ligand reorganization in the stoichiometric and catalytic activity of REIII ions.

The Role of Mitochondrial Calcium Homeostasis in Alzheimer's and Related Diseases.

Calcium signaling is essential for neuronal function, and its dysregulation has been implicated across neurodegenerative diseases, including Alzheimer's disease (AD). A close reciprocal relationship exists between calcium signaling and mitochondrial function. Growing evidence in a variety of AD models indicates that calcium dyshomeostasis drastically alters mitochondrial activity which, in turn, drives neurodegeneration. This review discusses the potential pathogenic mechanisms by which calcium impairs mitochondrial function in AD, focusing on the impact of calcium in endoplasmic reticulum (ER)-mitochondrial communication, mitochondrial transport, oxidative stress, and protein homeostasis. This review also summarizes recent data that highlight the need for exploring the mechanisms underlying calcium-mediated mitochondrial dysfunction while suggesting potential targets for modulating mitochondrial calcium levels to treat neurodegenerative diseases such as AD.

Fitness costs associated with multiple resistance to dicamba and atrazine in Chenopodium album.

MAIN CONCLUSION: Detrimental pleiotropic effects of resistance mutation(s) were observed for multiple-resistant phenotypes (resistant to both atrazine and dicamba). The multiple-resistant phenotypes had lower growth rates and less capacity for vegetative growth compared to the phenotypes only resistant to atrazine. The fitness costs that are conferred by herbicide resistance alleles can affect the rate of herbicide resistance evolution within populations. We evaluated the direct fitness costs involved with multiple resistance to dicamba and atrazine (R1 and R2) in Chenopodium album by comparing the performance of multiple-resistant phenotypes to those phenotypes that were only resistant to atrazine (S1 and S2). The R1 and R2 phenotypes were consistently shorter and produced less dry matter than the S1 and S2 phenotypes. The R1 and R2 phenotypes were shown to have lower relative growth rates (RGR) and net assimilation rates (NAR) than the S1 and S2 phenotypes at an early stage of growth. However, there was no significant difference in RGR between the R1 and R2 and, S1 and S2 phenotypes at a later stage of growth, though the R1 and R2 phenotypes still had a lower NAR at this later stage. Further investigations using a neighbouring crop competition approach showed that the R1 and R2 phenotypes were weaker competitors, and exhibited significantly less capacity for vegetative growth compared to the S1 and S2 phenotypes during competition. Overall, the results of this study revealed multiple- resistance to atrazine and dicamba endowed a significant fitness penalty to C. album, and it is possible that the frequency of multiple-resistant individuals would gradually decline once selection pressure from herbicides was discontinued.

Catalyst-Loaded Capsules that Spontaneously Inflate and Violently Eject their Core.

We present a design for polymer capsules that exhibit a range of unusual autonomous behaviors when exposed to a chemical fuel. The capsules have a physically gelled core (alginate-Ca2+) loaded with catalytic (silver) particles and a shell composed of a chemically cross-linked gel. In the presence of the fuel (H2O2), a catalytic reaction occurs, which generates oxygen (O2) gas. The gas collects in a zone between the core and the shell, and the resulting gas pressure causes the elastic shell to stretch. This makes the capsule inflate in a process reminiscent of a swelling pufferfish. As the capsule inflates, the polymer chains in the shell continue to stretch until a breaking point is reached, whereupon the shell ruptures. Three rupture modes are documented: gentle, moderate, and violent. The latter involves the gelled core being forcefully ejected out of the shell in a manner similar to the ejection of needles out of nematocysts on jellyfish. The extent and duration of inflation can be tuned by altering the core and shell composition; for example, shells that are more densely cross-linked swell less and rupture faster. Also, instead of a catalytic reaction, capsule inflation can be achieved by combining reactants, one in the capsule and the other in the external solution, that together generate a different gas (e.g., CO2).

Factors influencing fall prevention for patients with spinal cord injury from the perspectives of administrators in Canadian rehabilitation hospitals.

BACKGROUND: Fall prevention is a priority in Canadian tertiary rehabilitation hospitals. We aimed to understand the perspectives of hospital administrators on the challenges experienced when implementing fall prevention policies/procedures for patients with spinal cord injury (SCI) in tertiary rehabilitation hospitals. METHODS: Semi-structured interviews were conducted with 10 administrators employed in six Canadian tertiary rehabilitation hospitals. Guided by an interpretive description framework, interviews were analyzed using a constant comparison approach. RESULTS: Challenges with fall prevention experienced by administrators fell into the three categories: 1) fall prevention policy and procedural challenges (e.g. fall prevention policy not SCI-specific, expectation of zero falls, determining contributing factors, learning from falls, and overall effectiveness of the fall prevention policy), 2) clinician-related challenges (e.g. variable staff adherence with the organizations' fall prevention procedures, inconsistent delivery of fall prevention education, and integrating individualized fall risks to guide clinical practice), and 3) patient-related challenges (e.g. balancing risk vs independence and rehabilitation progress, responsibility for fall prevention, and non-preventable falls). CONCLUSIONS: Fall prevention policies/procedures required by the hospitals were insufficient for clinical practice in SCI rehabilitation.

Effect on herbicide adsorption of organic forestry waste products used for soil remediation.

Organic soil amendments can be useful for improving degraded soil, but this increase in organic matter (OM) may influence adsorption of herbicides subsequently applied to the treated soil, even though the particle size of amendments and their nature differ from typical soil OM. In this study, a batch equilibrium method was used to measure adsorption of five herbicides following application to two organic media, wood pulp and sawdust, comparing these with two cropping soils. Herbicide adsorption, quantified by distribution coefficients (kd), was much higher in the two organic media than in the cropping soils. The increases in adsorption were strongly correlated to the percentage of organic carbon. When the kd was normalized to adsorption coefficients corrected for OM content (koc), variation in results between the media was greatly reduced, indicating that OM is an important factor influencing adsorption in these media. The results of this study suggest that herbicides will be less effective when applied to soils in which sawdust and wood pulp have been added. Using organic amendments to remediate soil will increase adsorption of pesticides, reducing their bio-availability and efficacy, but also reducing their tendency to leach into root zones of deep-rooted crops and into groundwater.

Perioperative passport: empowering people with diabetes along their surgical journey.

AIM: To determine whether a handheld 'perioperative passport' could improve the experience of perioperative care for people with diabetes and overcome some of the communication issues commonly identified in inpatient extracts. METHODS: Individuals with diabetes undergoing elective surgery requiring at least an overnight stay were identified via a customized information technology system. Those allocated to the passport group were given the perioperative passport before their hospital admission. A 26-item questionnaire was completed after surgery by 50 participants in the passport group (mean age 69 years) and by 35 participants with diabetes who followed the usual surgical pathway (mean age 70 years). In addition, the former group had a structured interview about their experience of the passport. RESULTS: The prevalence of those who reported having received prior information about their expected diabetes care was 35% in the control group vs 92% in the passport group (P<0.001). The passport group found the information given significantly more helpful (P<0.001), including the advice on medication adjustment (P=0.008). Furthermore, those with the passport were more involved in planning their diabetes care (P <0.001), less anxious whilst in hospital (P<0.044) and better prepared to manage their diabetes on discharge (P≤0.001). The mean length of hospital stay was shorter in the passport group, although the difference did not reach significance (4.4 vs 6.5 days; P<0.058). Content analysis indicated that the passport was well liked and innovative. CONCLUSION: Our data indicate that the perioperative passport is effective in both informing and involving people in their diabetes care throughout the perioperative period.

Copper Causes Regiospecific Formation of C4 F8 -Containing Six-Membered Rings and their Defluorination/Aromatization to C4 F4 -Containing Rings in Triphenylene/1,4-C4 F8 I2 Reactions.

The presence of Cu in reactions of triphenylene (TRPH) and 1,4-C4 F8 I2 at 360 °C led to regiospecific substitution of TRPH ortho C(ß) atoms to form C4 F8 -containing rings, completely suppressing substitution on C(α) atoms. In addition, Cu caused selective reductive-defluorination/aromatization (RD/A) to form C4 F4 -containing aromatic rings. Without Cu, the reactions of TRPH and 1,4-C4 F8 I2 were not regiospecific and no RD/A was observed. These results, supported by DFT calculations, are the first examples of Cu-promoted 1) regiospecific perfluoroannulation, 2) preparative C-F activation, and 3) RD/A. HPLC-purified products were characterized by X-ray diffraction, low-temperature PES, and (1) H/(19) F NMR.

Incremental Tuning Up of Fluorous Phenazine Acceptors.

In a simple, one-step direct trifluoromethylation of phenazine with CF3 I we prepared and characterized nine (poly)trifluoromethyl derivatives with up to six CF3 groups. The electrochemical reduction potentials and gas-phase electron affinities show a direct, strict linear relation to the number of CF3 groups, with phenazine(CF3)6 reaching a record-high electron affinity of 3.24 eV among perfluoroalkylated polyaromatics.

Co-trending of parathyroid hormone and phosphate in patients receiving hemodialysis.

AIM: The objective of this study was to examine the time-varying relationship of chronic kidney disease-mineral bone disorder (CKD-MBD) related biochemical parameters (parathyroid hormone (PTH), calcium, phosphate) over a 12-month period. MATERIAL AND METHODS: Using data from a large US provider of dialysis services from 2010 through 2012, we constructed a cohort of adult patients receiving in-center hemodialysis who had biochemical parameters measured at both baseline and 12 months of follow-up. We used descriptive statistics to assess the overall distributions of the biochemical parameters at both measurements, to examine how patients transitioned between categories for each biochemical parameter, and to evaluate how the biochemical parameters changed with respect to each other. RESULTS: Among the 132,087 patients included in our analyses, the cross-sectional distributions for the combined categories of 150 - < 300 and 300 - < 600 pg/mL for PTH between the two measurements remained unchanged (67% of patients). For calcium and phosphate, the distributions across all categories also remained largely unchanged. Considering within-patient changes over time. however, a majority (74%) of patients who initially had a PTH < 150 pg/mL transitioned to a higher category, while a majority (56%) of patients who initially had a PTH > 600 pg/mL transitioned to a lower category. We observed that phosphate values on average directly trended with PTH values over the follow-up period. CONCLUSION: We found that while calcium showed relatively little variation, parallel bidirectional variation in PTH and phosphate over time was quite common among adult patients receiving hemodialysis. Optimal control of phosphate is likely to be dependent not only on consistent adherence to dietary restrictions and phosphate binders, but may additionally rely on adequate and sustained control of PTH.

Using Literature Review and Structured Hybrid Electronic/ Manual Mortality Review to Identify System-Level Improvement Opportunities to Reduce Colorectal Cancer Mortality.

BACKGROUND: Despite colorectal cancer (CRC) screening and survival rates exceeding national averages in the United States, Kaiser Permanente Southern California (KPSC) aimed to identify system-level improvement opportunities to further reduce mortality from CRC. METHODS: To examine modifiable factors contributing to CRC mortality, a structured hybrid electronic/manual mor- tality review was used to examine 50 randomly selected cases among 524 individuals aged 25-75 years diagnosed with stage II, III, or IV CRC after July 2008 who subsequently died. Physicians conducted chart reviews using a standardized data extraction tool based on evidence-based best practices. RESULTS: Eighty-six percent (43) of the 50 decedents were initially diagnosed with stage III or IV CRC; two cases of appendiceal cancer were excluded. Thirty-one percent (15) of the remaining 48 cases presented with no history of screening; 15% (7) had documented iron deficiency anemia and abdominal pain or rectal bleeding; and 6% (3) had no follow-up colonoscopy after positive screening. Eleven (52%) of the 21 patients with initial stage II-III CRC received appropriate surveillance after curative surgery; 57% (12) developed metastases. Adjuvant chemotherapy was offered to 88% (14/16) of patients with stage III (node-positive) CRC; chemotherapy initiation was delayed in 6 patients. Missed opportunities for surgical oncology evaluation occurred among 61% (11/18) of patients with liver metastases at diagnosis. Failure to report clinically significant features on pathology occurred in 2 patients; they received appropriate treatment for other reasons. CONCLUSIONS: Improvement opportunities existed at multiple stages of care, including screening, evaluation of symp toms, timeliness of care, use of adjuvant chemotherapy, and surgical oncology practices.

Impact of the Diabetes Inpatient Care and Education (DICE) project and the DICE Care Pathway on patient outcomes and trainee doctor's knowledge and confidence.

AIM: To evaluate the impact of the Diabetes Inpatient Care and Education project and a comprehensive diabetes care pathway, the Diabetes Inpatient Care and Education Care Pathway, on patient outcomes and on the knowledge and confidence of trainee doctors. METHODS: The effect on patient outcomes was evaluated by comparing the National Diabetes Inpatient Audit data before (2012) and after (2013) implementing the Diabetes Inpatient Care and Education project. The impact on trainee doctors was evaluated using the Modified Kirkpatrick model. Just before the project began and again 3 months later, trainee doctors were surveyed to assess their knowledge and confidence in inpatient diabetes care. RESULTS: Patient harm was found to have been reduced significantly when National Diabetes Inpatient Audit data for 2012 and 2013 were compared. Severe hypoglycaemia decreased from 15.4 to 9.7%, medication errors from 56.9 to 21.1% and insulin errors from 31 to 7%. Across the 96 trainee doctors surveyed, the mean (sd) knowledge and confidence scores increased significantly (P < 0.001 for both) from 57.1 (16.8) and 61.8 (14.9) to 68.4 (13.3) and 74.3 (11.7), respectively. CONCLUSION: The Diabetes Inpatient Care and Education project and the Diabetes Inpatient Care and Education Care Pathway improved patient outcomes and the knowledge and confidence of trainee doctors in this hospital. The impact of a similar project in other hospitals needs to be evaluated.

Chronic opiate use in pregnancy and newborn head circumference.

OBJECTIVE: The aim of the study is to evaluate whether chronic opiate use in pregnancy affects newborn head circumference (HC). STUDY DESIGN: All newborns from January 1, 2010, to June 30, 2012, admitted to the neonatal intensive care unit for treatment of neonatal abstinence syndrome were prospectively collected. The demographic, obstetrical, neonatal, and perinatal ultrasound data were retrospectively obtained. A gestational age-matched control was used for comparison purposes. RESULTS: Of 332 neonates admitted for the treatment of neonatal abstinence syndrome, 98 (29.5%) had a HC ≤ 10th percentile for gestational age that was significantly increased when compared with controls (p < 0.001). Of these 98, 25 had a HC ≤ 3rd percentile. Of the case population, 141 had an ultrasound in the perinatal unit within 10 days of birth. A HC < 5th percentile was found in 38.3% of cases of which 74% were ≤ 10th percentile postdelivery. The ultrasound femur and humerus length measurements were also < 5th percentile in 36.2 and 28.9%, respectively. CONCLUSION: Chronic opiate use in pregnancy appears to increase the risk for a HC ≤ 10th percentile and ≤ 3rd percentile when compared with controls. From ultrasound findings, femur and humerus lengths also appear to be shortened suggesting a possible effect on bone growth.

Rapid identification of Helicoverpa armigera and Helicoverpa zea (Lepidoptera: Noctuidae) using ribosomal RNA internal transcribed spacer 1.

Rapid identification of invasive species is crucial for deploying management strategies to prevent establishment. Recent Helicoverpa armigera (Hübner) invasions and subsequent establishment in South America has increased the risk of this species invading North America. Morphological similarities make differentiation of H. armigera from the native Helicoverpa zea (Boddie) difficult. Characteristics of adult male genitalia and nucleotide sequence differences in mitochondrial DNA are two of the currently available methods to differentiate these two species. However, current methods are likely too slow to be employed as rapid detection methods. In this study, conserved differences in the internal transcribed spacer 1 (ITS1) of the ribosomal RNA genes were used to develop species-specific oligonucleotide primers that amplified ITS1 fragments of 147 and 334 bp from H. armigera and H. zea, respectively. An amplicon (83 bp) from a conserved region of 18S ribosomal RNA subunit served as a positive control. Melting temperature differences in ITS1 amplicons yielded species-specific dissociation curves that could be used in high resolution melt analysis to differentiate the two Helicoverpa species. In addition, a rapid and inexpensive procedure for obtaining amplifiable genomic DNA from a small amount of tissue was identified. Under optimal conditions, the process was able to detect DNA from one H. armigera leg in a pool of 25 legs. The high resolution melt analysis combined with rapid DNA extraction could be used as an inexpensive method to genetically differentiate large numbers of H. armigera and H. zea using readily available reagents.

Immune status influences fear and anxiety responses in mice after acute stress exposure.

Significant evidence suggests that exposure to traumatic and/or acute stress in both mice and humans results in compromised immune function that in turn may affect associated brain processes. Additionally, recent studies in mouse models of immune deficiency have suggested that adaptive immunity may play a role during traumatic stress exposure and that impairments in lymphocyte function may contribute to increased susceptibility to various psychogenic stressors. However, rodent studies on the relationship between maladaptive stress responses and lymphocyte deficiency have been complicated by the fact that genetic manipulations in these models may also result in changes in CNS function due to the expression of targeted genes in tissues other than lymphocytes, including the brain. To address these issues we utilized mice with a deletion of recombination-activating gene 2 (Rag2), which has no confirmed expression in the CNS; thus, its loss should result in the absence of mature lymphocytes without altering CNS function directly. Stress responsiveness of immune deficient Rag2(-/-) mice on a BALB/c background was evaluated in three different paradigms: predator odor exposure (POE), fear conditioning (FC) and learned helplessness (LH). These models are often used to study different aspects of stress responsiveness after the exposure to an acute stressor. In addition, immunoblot analysis was used to assess hippocampal BDNF expression under both stressed and non-stressed conditions. Subsequent to POE, Rag2(-/-) mice exhibited a reduced acoustic startle response compared to BALB/c mice; no significant differences in behavior were observed in either FC or LH. Furthermore, analysis of hippocampal BDNF indicated that Rag2(-/-) mice have elevated levels of the mature form of BDNF compared to BALB/c mice. Results from our studies suggest that the absence of mature lymphocytes is associated with increased resilience to stress exposure in the POE and does not affect behavioral responses in the FC and LH paradigms. These findings indicate that lymphocytes play a specific role in stress responsiveness dependent upon the type, nature and intensity of the stressor.