Development and implementation of an injury and illness surveillance system for team USA.

BACKGROUND: The purpose of this report is to provide insight and details regarding the development and implementation of an injury and illness surveillance (IIS) system for the United States Olympic and Paralympic Committee (USOPC). METHODS: The development and deployment of the IIS employed a multiphase approach. First, researchers determined variables to include in the IIS using the recommendations from the 2020 IOC consensus statement for reporting sport epidemiological data. Second, the hosting and deployment platforms were comprehensively evaluated for their suitability, ease of use, flexibility, and backend data structure (for both capture and aggregation). Third, focus groups consisting of the Sports Medicine department leadership and clinicians piloted the IIS system and revisions were made based on their feedback. Pilot testing of the IIS and follow-up focus groups were then conducted among all departmental clinicians to solicit additional feedback and drive further revisions. Finally, the IIS system was piloted among providers working during the 2023 Pan American and Parapan American Games to refine the system for future Games. After reviewing all potential software platform options (electronic medical record [EMR] system, athlete management systems, secure data collection platforms), Qualtrics (Qualtrics, Provo, UT, USA) was selected to host the IIS system. This choice was made due to the inability of the EMR and athlete-management systems to make frequent updates, modify existing questions, and provide the necessary form logic for the variety of scenarios in which the IIS system would be deployed. Feedback from the department's leadership and clinicians resulted in a number of changes, most notably being the ability to enter multiple diagnoses for a single injury event. Additionally, clinician feedback resulted in the creation of additional diagnostic codes not currently present in the OSIICS v14.0 diagnostic coding system, adding "non-sport" as an additional variable for injury setting, and developing a system for reporting return-to-sport date for time-loss injuries. DISCUSSION: A multi-stage process of extensive planning, stakeholder feedback, and ongoing updates is required in order to successfully develop and implement an IIS system within a National Olympic and Paralynpic Committee. This process can be used to inform the development and implementation of IIS systems in other sporting organizations.

High rates of respiratory illnesses upon arrival: lessons from Team USA at the Santiago 2023 Pan American and Parapan American Games.

OBJECTIVE: To describe the incidence and characteristics of injuries and illnesses among Team USA athletes competing at the Santiago 2023 Pan American Games (PAG) and Parapan American Games (PPAG), with a particular focus on the incidence of respiratory illnesses and on injuries for sports new to the Olympic and Paralympic programmes. METHODS: Illnesses and injuries occurring among the 870 Team USA athletes competing in the Santiago 2023 PAG or PPAG were documented within Team USA's Injury and Illness Surveillance system. Illness and injury incidence per 1000 athlete-days (ADs) and incidence ratios (IR) were calculated, both with 95% CIs. RESULTS: Illness (IR 2.5, 95% CI 1.6, 3.9) and injury (IR 1.8, 95% CI 1.3, 2.5) rates were greater during PPAG compared with PAG. Illness rates were higher in the pre-opening ceremony period compared with the competition period for both PAG (IR 2.7, 95% CI 1.1, 5.9) and PPAG (IR 1.9, 95% CI 0.9, 3.8). Respiratory illness was the most common illness with 3.2% and 8.9% of all Team USA athletes reporting a respiratory illness during the PAG and PPAG, respectively. Sports that are relatively new to the Olympic/Paralympic programmes exhibited the highest injury rates during the Games: breaking (250.0 (91.7, 544.2) per 1000 ADs), Para taekwondo (93.8 (19.3, 274.0) per 1000 ADs) and surfing (88.9 (24.2, 227.6) per 1000 ADs). CONCLUSION: Respiratory illness rates were the most common type of illness during both PAG and PPAG and were more likely to occur prior to competition starting. Our data have identified high injury risk populations (breaking, surfing, Para taekwondo) and timing (pre-opening ceremony period) for further risk factor analysis.

A phase II study of potentiation of pembrolizumab with binimetinib and bevacizumab in refractory microsatellite stable colorectal cancer.

PURPOSE: In this single-institution phase II investigator-initiated study we assessed the ability of MAPK and VEGF pathway blockade to overcome resistance to immunotherapy in microsatellite stable metastatic colorectal cancer (MSS mCRC). PATIENTS AND METHODS: Patients with MSS, BRAF wild-type mCRC who progressed on ≥2 prior lines of therapy received pembrolizumab, binimetinib, and bevacizumab until disease progression or unacceptable toxicity. After a safety run-in, patients were randomized to a 7-day run-in of binimetinib or simultaneous initiation of all study drugs, to explore whether MEK inhibition may increase tumor immunogenicity. The primary endpoint was objective response rate in all patients combined (ORR, by RECIST v1.1). RESULTS: Fifty patients received study drug treatment; 54% were male with median age 55 years (range 31-79). The primary endpoint, ORR, was 12.0% (95% confidence interval [CI] 4.5-24.3%), which was not statistically different than the historical control data of 5% (p=0.038, exceeding pre-specified threshold of 0.025). The disease control rate was 70.0% (95% CI 55.4-82.1%), median progression-free survival 5.9 months (95% CI 4.2-8.7 months), and median overall survival 9.3 months (95% CI 6.7-12.2 months). No difference in efficacy was observed between the randomized cohorts. Grade 3 and 4 adverse events were observed in 56% and 8% of patients, respectively; the most common were rash (12%) and increased aspartate aminotransferase (12%). CONCLUSION: Pembrolizumab, binimetinib, and bevacizumab failed to meet its primary endpoint of higher ORR compared to historical control data, demonstrated a high disease control rate, and demonstrated acceptable tolerability in refractory MSS mCRC.

De Novo Synthesis and Structural Elucidation of CDR-H3 Loop Mimics.

The binding affinity of antibodies to specific antigens stems from a remarkably broad repertoire of hypervariable loops known as complementarity-determining regions (CDRs). While recognizing the pivotal role of the heavy-chain 3 CDRs (CDR-H3s) in maximizing antibody-antigen affinity and specificity, the key structural determinants responsible for their adaptability to diverse loop sequences, lengths, and noncanonical structures are hitherto unknown. To address this question, we achieved a de novo synthesis of bulged CDR-H3 mimics excised from their full antibody context. CD and NMR data revealed that these stable standalone ß-hairpin scaffolds are well-folded and retain many of the native bulge CDR-H3 features in water. In particular, the tryptophan residue, highly conserved across CDR-H3 sequences, was found to extend the kinked base of these ß-bulges through a combination of stabilizing intramolecular hydrogen bond and CH/π interaction. The structural ensemble consistent with our NMR observations exposed the dynamic nature of residues at the base of the loop, suggesting that ß-bulges act as molecular hinges connecting the rigid stem to the more flexible loops of CDR-H3s. We anticipate that this deeper structural understanding of CDR-H3s will lay the foundation to inform the design of antibody drugs broadly and engineer novel CDR-H3 peptide scaffolds as therapeutics.

Heart rate variability-based prediction of early cardiotoxicity in breast-cancer patients treated with anthracyclines and trastuzumab.

BACKGROUND: Cardiotoxicity is a recognized complication in breast cancer (BC) patients undergoing chemotherapy with anthracyclines with or without trastuzumab. However, the prognostic value of heart rate variability (HRV) indexes for early cardiotoxicity development remains unknown. METHODS: Fifty BC patients underwent TTE assessment before and three months after chemotherapy. HRV indexes were obtained from continuous electrocardiograms in supine position with spontaneous breathing, active standing, and supine position with controlled breathing. The magnitude of change (Δ) between supine-standing and supine-controlled breathing was calculated. Variables were compared using t-test or ANOVA. Cardiotoxicity predictive value was assessed by ROC curve analysis. A p value of < 0.05 was considered significant. RESULTS: TTE revealed reduced left atrial conduit strain in the cardiotoxicity group. Mean heart rate increased during all maneuvers at follow-up, with no differences in HRV indexes between patients with or without cardiotoxicity. However, a lower Δ in supine-controlled breathing of several HRV indexes predicted early cardiotoxicity identified by echocardiography (e.g. SDNN ≤ -8.44 ms: Sensitivity = 75%, Specificity = 69%). CONCLUSIONS: BC patients treated with chemotherapy maintain cardiac autonomic responses to physiological stimuli after 3 months of chemotherapy. However, a lower Δ during active standing and controlled breathing before chemotherapy may predict early cardiotoxicity.

Deep brain stimulation of the amygdala for treatment-resistant combat post-traumatic stress disorder: Long-term results.

Deep brain stimulation (DBS) holds promise for neuropsychiatric conditions where imbalance in network activity contributes to symptoms. Treatment-resistant Combat post-traumatic stress disorder (TR-PTSD) is a highly morbid condition and 50% of PTSD sufferers fail to recover despite psychotherapy or pharmacotherapy. Reminder-triggered symptoms may arise from inadequate top-down ventromedial prefrontal cortex (vmPFC) control of amygdala reactivity. Here, we report long-term data on two TR-PTSD participants from an investigation utilizing high-frequency amygdala DBS. The two combat veterans were implanted bilaterally with quadripolar electrodes targeting the basolateral amygdala. Following a randomized staggered onset, patients received stimulation with adjustments based on PTSD symptom severity for four years while psychiatric and neuropsychiatric symptoms, neuropsychological performance, and electroencephalography were systematically monitored. Evaluation of vmPFC-Amygdala network engagement was assessed with 18FDG positron emission tomography (PET). CAPS-IV scores varied over time, but improved 55% from 119 at baseline to 53 at 4-year study endpoint in participant 1; and 44%, from 68 to 38 in participant 2. Thereafter, during 5 and 1.5 years of subsequent clinical care respectively, long-term bilateral amygdala DBS was associated with additional, clinically significant symptomatic and functional improvement. There were no serious stimulation-related adverse psychiatric, neuropsychiatric, neuropsychological, neurological, or neurosurgical effects. In one subject, symptomatic improvement was associated with an intensity-dependent reduction in amygdala theta frequency power. In our two participants, FDG-PET findings were inconclusive regarding the hypothesized mechanism of suppression of amygdala hyperactivity. Our findings encourage further research to confirm and extend our preliminary observations.

A Phase Ib Expansion Cohort Evaluating Aurora A Kinase Inhibitor Alisertib and Dual TORC1/2 Inhibitor Sapanisertib in Patients with Advanced Solid Tumors.

BACKGROUND: This study further evaluated the safety and efficacy of the combination of alisertib and sapanisertib in an expansion cohort of patients, including a subset of patients with refractory pancreatic adenocarcinoma, with further evaluation of the pharmacodynamic characteristics of combination therapy. METHODS: Twenty patients with refractory solid tumors and 11 patients with pancreatic adenocarcinoma were treated at the recommended phase 2 dose of alisertib and sapanisertib. Adverse events and disease response were assessed. Patients in the expansion cohort were treated with a 7-day lead-in of either alisertib or sapanisertib prior to combination therapy, with tumor tissue biopsy and serial functional imaging performed for correlative analysis. RESULTS: Toxicity across treatment groups was overall similar to prior studies. One partial response to treatment was observed in a patient with ER positive breast cancer, and a patient with pancreatic cancer experienced prolonged stable disease. In an additional cohort of pancreatic cancer patients, treatment response was modest. Correlative analysis revealed variability in markers of apoptosis and immune cell infiltrate according to lead-in therapy and response. CONCLUSIONS: Dual targeting of Aurora A kinase and mTOR resulted in marginal clinical benefit in a population of patients with refractory solid tumors, including pancreatic adenocarcinoma, though individual patients experienced significant response to therapy. Correlatives indicate apoptotic response and tumor immune cell infiltrate may affect clinical outcomes.

Examination of Wnt signaling as a therapeutic target for pancreatic ductal adenocarcinoma (PDAC) using a pancreatic tumor organoid library (PTOL).

Pancreatic ductal adenocarcinoma (PDAC) presents at advanced stages and is refractory to most treatment modalities. Wnt signaling activation plays a critical role in proliferation and chemotherapeutic resistance. Minimal media conditions, growth factor dependency, and Wnt dependency were determined via Wnt inhibition for seven patient derived organoids (PDOs) derived from pancreatic tumor organoid libraries (PTOL). Organoids demonstrating response in vitro were assessed in vivo using patient-derived xenografts. Wnt (in)dependent gene signatures were identified for each organoid. Panc269 demonstrated a trend of reduced organoid growth when treated with ETC-159 in combination with paclitaxel or gemcitabine as compared with chemotherapy or ETC-159 alone. Panc320 demonstrated a more pronounced anti-proliferative effect in the combination of ETC-159 and paclitaxel but not with gemcitabine. Panc269 and Panc320 were implanted into nude mice and treated with ETC-159, paclitaxel, and gemcitabine as single agents and in combination. The combination of ETC-159 and paclitaxel demonstrated an anti-tumor effect greater than ETC-159 alone. Extent of combinatory treatment effect were observed to a lesser extent in the Panc320 xenograft. Wnt (in)dependent gene signatures of Panc269 and 320 were consistent with the phenotypes displayed. Gene expression of several key Wnt genes assessed via RT-PCR demonstrated notable fold change following treatment in vivo. Each pancreatic organoid demonstrated varied niche factor dependencies, providing an avenue for targeted therapy, supported through growth analysis following combinatory treatment of Wnt inhibitor and standard chemotherapy in vitro. The clinical utilization of this combinatory treatment modality in pancreatic cancer PDOs has thus far been supported in our patient-derived xenograft models treated with Wnt inhibitor plus paclitaxel or gemcitabine. Gene expression analysis suggests there are key Wnt genes that contribute to the Wnt (in)dependent phenotypes of pancreatic tumors, providing plausible mechanistic explanation for Wnt (in)dependency and susceptibility or resistance to treatment on the genotypic level.

The extrastriate symmetry response is robust to alcohol intoxication.

Visual symmetry activates a network of regions in the extrastriate cortex and generates an event-related potential (ERP) called the sustained posterior negativity (SPN). Previous work has found that the SPN is robust to experimental manipulations of task, spatial attention, and memory load. In the current study, we investigated whether the SPN is also robust to alcohol-induced changes in mental state. A pilot experiment (N = 13) found that alcohol unexpectedly increased SPN amplitude. We followed this unexpected result with two new experiments on separate groups, using an alcohol challenge paradigm. One group completed an Oddball discrimination task (N = 26). Another group completed a Regularity discrimination task (N = 26). In both groups, participants consumed a medium dose of alcohol (0.65 g/kg body weight) and a placebo drink, in separate sessions. Alcohol reduced SPN amplitude in the Oddball task (contrary to the pilot results) but had no effect on SPN amplitude in the Regularity task. In contrast, the N1 wave was consistently dampened by alcohol in all experiments. Exploratory analysis indicated that the inconsistent effect of alcohol on SPN amplitude may be partly explained by individual differences in alcohol use. Alcohol reduced the SPN in light drinkers and increased it in heavier drinkers. Despite remaining questions, the results highlight the automaticity of symmetry processing. Symmetry still produces a large SPN response, even when participants are intoxicated, and even when symmetry is not task relevant.

Management of complex pediatric and adolescent liver trauma: adult vs pediatric level 1 trauma centers.

PURPOSE: Management of high-grade pediatric and adolescent liver trauma can be complex. Studies suggest that variation exists at adult (ATC) vs pediatric trauma centers (PTC); however, there is limited granular comparative data. We sought to describe and compare the management and outcomes of complex pediatric and adolescent liver trauma between a level 1 ATC and two PTCs in a large metropolitan city. METHODS: A retrospective review of pediatric and adolescent (age < 21 years) patients with American Association for the Surgery of Trauma (AAST) Grade 4 and 5 liver injuries managed at an ATC and PTCs between 2016 and 2022 was performed. Demographic, clinical, and outcome data were obtained at the ATC and PTCs. Primary outcomes included rates of operative management and use of interventional radiology (IR). Secondary outcomes included packed red blood cell (pRBC) utilization, intensive care unit (ICU) length of stay (LOS), and hospital LOS. RESULTS: One hundred forty-four patients were identified, seventy-five at the ATC and sixty-nine at the PTC. The cohort was predominantly black (65.5%) males (63.5%). Six injuries (8.7%) at the PTC and forty-five (60%) injuries at the ATC were penetrating trauma. Comparing only blunt trauma, ATC patients had higher Injury Severity Score (median 37 vs 26) and ages (20 years vs 9 years). ATC patients were more likely to undergo operative management (26.7% vs 11.0%, p = 0.016) and utilized IR more (51.9% vs 4.8%, p < 0.001) compared to the PTC. The patients managed at the ATC required higher rates of pRBC transfusions though not statistically significant (p = 0.06). There were no differences in mortality, ICU, or hospital LOS. CONCLUSION: Our retrospective review of high-grade pediatric and adolescent liver trauma demonstrated higher rates of IR and operating room use at the ATC compared to the PTC in the setting of higher Injury Severity Score and age. While the PTC successfully managed > 95% of Grade 4/5 liver injuries non-operatively, prospective data are needed to determine the optimal algorithm for management in the older adolescent population. LEVEL OF EVIDENCE: Level IV.

Event related potentials (ERP) reveal a robust response to visual symmetry in unattended visual regions.

Visual symmetry at fixation generates a bilateral Event Related Potential (ERP) called the Sustained Posterior Negativity (SPN). Symmetry presented in the left visual hemifield generates a contralateral SPN over the right hemisphere and vice versa. The current study examined whether the contralateral SPN is modulated by the focus of spatial attention. On each trial there were two dot patterns, one to the left of fixation, and one to the right of fixation. A central arrow cue pointed to one of the patterns and participants discriminated its regularity (symmetry or random). We compared contralateral SPN amplitude generated by symmetry at attended and unattended spatial locations. While the response to attended symmetry was slightly enhanced, the response to unattended symmetry was still substantial. Although visual symmetry detection is a computational challenge, we conclude that the brain processes visual symmetry in unattended parts of the visual field.

Creating healthy eating and active environments in early learning settings: protocol of the CHEERS eHealth intervention study.

Background: Early childhood educators through their daily interactions with children, play a central role in shaping young children's health behaviors. Given their influential role, early childhood educators are often targeted in interventions aiming at enhancing their nutrition and physical activity practices. Methods: This paper presents the design of the CHEERS eHealth program to improve nutrition and physical activity practices within Early Childhood Education and Care (ECEC) centers. The study has a longitudinal quasi-experimental design with recruitment of ECECs across Alberta Canada. ECEC intervention group educators complete 12 weekly online nutrition and physical activity modules and participate in weekly communities of practice sessions to discuss practical applications within their centers. Outcome assessments are scheduled at baseline (T1), mid-point at 5 months (T2), and end of program after 10 months (T3). Outcome measures include the Creating Healthy Eating and Active Environments survey (CHEERS), Mindful Eating Questionnaire (MEQ), Canadian Behavior, Attitude and Nutrition Knowledge Survey (C-BANKS 2.0), Physical Literacy Knowledge, Attitude, Self-Efficacy, and Behavior (PLKASB-ECE), the Environment and Policy Assessment and Observation (EPAO) derived variables, and an objective measure of children's physical activity using ActiGraph GT3X accelerometers. Linear mixed model analyses will be used to evaluate the effectiveness of the intervention. Qualitative assessments comprise exit interviews and open-response questions embedded within the educational modules. Results: Preliminary baseline data from the 2019 cohort indicate no statistically significant differences between the intervention and control groups for the primary outcome variables, except age. Educators' personal nutrition-related knowledge, attitude and behaviors were positively associated with their self-assessments of the nutrition environment and practices in ECECs. A significant correlation was observed between educators' self-reported physical activity practices and observed activity practices. The CHEERS survey Food Served subscale showed a positive correlation with the objective measures of EPAO-Foods Provided and Nutrition Policy subdomains. Discussion: We propose that this eHealth intervention would be an effective scaling up approach to enhancing the nutrition and physical activity environments of ECECs by fostering improved nutrition and physical activity-related knowledge, attitudes, and adherence to best practices which will potentially lead to improved outcomes for children in their care.

The Impact of an Overactive Bladder Care Pathway on Longitudinal Patient Management.

IMPORTANCE: Implementation of an overactive bladder (OAB) care pathway may affect treatment patterns and progression. OBJECTIVES: This study aimed to assess the effect of OAB care pathway implementation on treatment patterns for women with OAB. STUDY DESIGN: This retrospective cohort study evaluated women with OAB, before (January 1, 2015-December 31, 2017) and after (January 1, 2019-December 31, 2021) care pathway initiation. Care pathway use included standardized counseling, early introduction of therapy, and close follow-up. Primary outcomes included OAB medication use, follow-up visits, third-line therapy, and time to third-line therapy. RESULTS: A total of 1,349 women were included: 1,194 before care pathway implementation and 155 after. Patients after implementation were more likely to have diabetes mellitus (P = 0.04) and less likely to smoke (P = 0.01). Those managed via a care pathway were more likely to use any medication or third-line therapy within 1 year after consultation (61.3% vs 25.0%; P < 0.001). This included higher proportions receiving a medication (50.3% [95% confidence interval (CI), 41.8%-57.6%] vs 23.3% [95% CI, 20.9%-25.7%]; P < 0.001) and progressing to third-line therapy (22.6% [95% CI, 15.7%-28.9%] vs 2.9% [95% CI, 2%-3.9%]; P < 0.001). Among those who underwent third-line treatment, care pathway use was associated with shorter time to third-line therapy (median, 10 days [interquartile range, 1-56 days] vs 29 days [interquartile range, 7-191 days]; P = 0.013). Those managed via a care pathway were less likely to have additional clinic visits for OAB within 1 year after initial consultation (12.3% vs 23.9%; P < 0.001). CONCLUSIONS: Use of an OAB care pathway was associated with higher rates of oral medication and third-line therapy yet decreased follow-up office visits. Use of an OAB care pathway may promote consistent and efficient care for women with OAB.

When does perceptual organization happen?

Reflectional (mirror) symmetry is an important visual cue for perceptual organization. The brain processes symmetry rapidly and efficiently. Previous work suggests that symmetry activates the extrastriate cortex and generates an event related potential (ERP) called the Sustained Posterior Negativity (SPN). It has been claimed that no tasks completely block symmetry processing and abolish the SPN. We tested the limits of this claim with a series of eight new Electroencephalography (EEG) experiments (344 participants in total). All experiments used the same symmetrical or asymmetrical dot patterns. When participants attended to regularity in Experiment 1, there was a substantial SPN (Mean amplitude = -2.423 µV). The SPN was reduced, but not abolished, when participants discriminated dot luminance in Experiments 2 and 3 (-.835 and -1.410 µV) or the aspect ratio of a superimposed cross in Experiments 4 and 5 (-.722 and -.601 µV). The SPN also survived when the background pattern was potentially disruptive to the primary task in Experiment 6 (-1.358 µV) and when participants classified negative superimposed words in Experiment 7 (-.510 µV). Finally, the SPN remained when participants attended to the orientation of a diagonal line in Experiment 8 (-.589 µV). While task manipulations can turn down the extrastriate symmetry activation, they cannot render the system completely unresponsive. Permanent readiness to detect reflectional symmetry at the centre of the visual field could be an evolved adaptation.

The brain does not process horizontal reflection when attending to vertical reflection, and vice versa.

Previous work has found that feature attention can modulate electrophysiological responses to visual symmetry. In the current study, participants observed spatially overlapping clouds of black and white dots. They discriminated vertical symmetry from asymmetry in the target dots (e.g., black or white) and ignored the regularity of the distractor dots (e.g., white or black). We measured an electroencephalography component called the sustained posterior negativity (SPN), which is known to be generated by visual symmetry. There were five conditions with different combinations of target and distractor regularity. As well as replicating previous results, we found that an orthogonal axes of reflection in the distractor dots had no effect on SPN amplitude. We conclude that the visual system can processes reflectional symmetry in independent axis-orientation specific channels.

Temporal associations between meaning in life, ultimate meaning struggles, and mental health outcomes in a spiritually integrated inpatient program.

BACKGROUND: Meaning in life is a benchmark indicator of flourishing that can likely mitigate the severity of depression symptoms among persons seeking mental healthcare. However, patients contending with serious mental health difficulties often experience a painful void or absence of ultimate meaning in their lives that might hinder recovery. This two-wave longitudinal study examined temporal associations between perceived presence of meaning in life, struggles with ultimate meaning, flourishing, and depression symptoms among adults in a spiritually integrated inpatient treatment program. METHODS: Of the 242 patients assessed at intake, 90% (N = 218; 40% Cisgender male; 57% Cisgender female; 3.0% nonbinary) completed validated measures of these meaning-related factors and mental health outcomes at discharge. RESULTS: Cross-sectional analyses revealed perceptions of meaning in life and ultimate meaning struggles were inversely linked with one another along with being associated with indices of positive and negative mental health in varying ways at the start and end of treatment. Drawing upon a two-wave cross-lagged panel design, longitudinal structural equation modeling analyses supported a Primary Meaning Model whereby having a subjective sense of meaning in life at intake was prospectively linked with lower levels of ultimate meaning struggles and greater flourishing at discharge. However, baseline levels of mental health outcomes were not predictive of the meaning-related factors in this sample. CONCLUSION: Findings highlight the utility of assessing patients' perceived meaning in life and ultimate meaning struggles in spiritually integrated programs and for clinicians to be prepared to possibly address these meaning-related concerns in the treatment process.

Immune Control in Repeated Babesia microti Infection in a Patient With B-Cell Deficiency.

The immunology of human babesiosis is poorly investigated. We present a comprehensive investigation of a 75-year-old man with B-cell deficiency who experienced 3 episodes of babesiosis over a 6-year period. Slowly evolving clinical immunity was observed, as evidenced by milder clinical symptoms and lower peak parasite burden after each subsequent babesiosis episode. The patient exhibited several striking immunologic findings. First, the patient had exceptionally high Babesia microti-specific antibodies despite very few circulating B cells, which predominantly coexpressed CD27 (memory marker) and CD95 (death receptor). Second, we demonstrated the presence of long-lasting NK cells and expansion of T memory stem cells. Third, levels of the IP-10 cytokine directly correlated with parasite burden. These results raise fundamental questions on the priming, maintenance, and location of a B-cell population that produces high antibody levels in the face of severe B-cell deficiency. Our results should invoke interest among researchers to study the immunology and pathogenesis of human babesiosis.