A unified metric of human immune health.

Immunological health has been challenging to characterize but could be defined as the absence of immune pathology. While shared features of some immune diseases and the concept of immunologic resilience based on age-independent adaptation to antigenic stimulation have been developed, general metrics of immune health and its utility for assessing clinically healthy individuals remain ill defined. Here we integrated transcriptomics, serum protein, peripheral immune cell frequency and clinical data from 228 patients with 22 monogenic conditions impacting key immunological pathways together with 42 age- and sex-matched healthy controls. Despite the high penetrance of monogenic lesions, differences between individuals in diverse immune parameters tended to dominate over those attributable to disease conditions or medication use. Unsupervised or supervised machine learning independently identified a score that distinguished healthy participants from patients with monogenic diseases, thus suggesting a quantitative immune health metric (IHM). In ten independent datasets, the IHM discriminated healthy from polygenic autoimmune and inflammatory disease states, marked aging in clinically healthy individuals, tracked disease activities and treatment responses in both immunological and nonimmunological diseases, and predicted age-dependent antibody responses to immunizations with different vaccines. This discriminatory power goes beyond that of the classical inflammatory biomarkers C-reactive protein and interleukin-6. Thus, deviations from health in diverse conditions, including aging, have shared systemic immune consequences, and we provide a web platform for calculating the IHM for other datasets, which could empower precision medicine.

Topical Steroid Withdrawal is a Targetable Excess of Mitochondrial NAD.

Background: Topical corticosteroids (TCS) are first-line therapies for numerous skin conditions. Topical Steroid Withdrawal (TSW) is a controversial diagnosis advocated by patients with prolonged TCS exposure who report severe systemic reactions upon treatment cessation. However, to date there have been no systematic clinical or mechanistic studies to distinguish TSW from other eczematous disorders. Methods: A re-analysis of a previous survey with eczematous skin disease was performed to evaluate potential TSW distinguishing symptoms. We subsequently conducted a pilot study of 16 patients fitting the proposed diagnostic criteria. We then performed: tissue metabolomics, transcriptomics, and immunostaining on skin biopsies; serum metabolomics and cytokine assessments; shotgun metagenomics on microbiome skin swabs; genome sequencing; followed by functional, mechanistic studies using human skin cell lines and mice. Results: Clinically distinct TSW symptoms included burning, flushing, and thermodysregulation. Metabolomics and transcriptomics both implicated elevated NAD+ oxidation stemming from increased expression of mitochondrial complex I and conversion of tryptophan into kynurenine metabolites. These abnormalities were induced by glucocorticoid exposure both in vitro and in a cohort of healthy controls (N=19) exposed to TCS. Targeting complex I via either metformin or the herbal compound berberine improved outcomes in both cell culture and in an open-label case series for patients with TSW. Conclusion: Taken together, our results suggest that TSW has a distinct dermatopathology. While future studies are needed to validate these results in larger cohorts, this work provides the first mechanistic evaluation into TSW pathology, and offers insights into clinical identification, pharmacogenomic candidates, and directed therapeutic strategies.

Management and outcome of COVID-19 in CTLA-4 insufficiency.

Despite the high incidence of COVID-19 worldwide, clinical experience with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) in inborn errors of immunity remains limited. Recent studies have shown that patients with defects in type 1 interferon (IFN)-related pathways or those with autoantibodies against type 1 IFNs develop severe COVID-19. We reported the clinical course of 22 patients with CTLA-4 insufficiency and COVID-19 and retrospectively examined autoantibodies against type 1 IFNs at baseline. Data were obtained from the patient interviews and chart reviews. Screening for anti-IFN autoantibodies was performed using a multiplex particle-based assay. Student t test, Mann Whitney, analysis of variance, or χ2 tests were used where appropriate. Twenty-two patients aged from 8 months to 54 years, with genetically confirmed CLTA-4 insufficiency, developed COVID-19 from 2020 to 2022. The most common symptoms were fever, cough, and nasal congestion, and the median duration of illness was 7.5 days. Twenty patients (91%) developed mild COVID-19 and were treated as outpatients. Two patients were hospitalized because of COVID-19 pneumonia but did not require mechanical ventilation. Ten (45%) patients were vaccinated at the time of their first COVID-19 infection. Eleven patients received outpatient treatment with monoclonal antibodies against the SARS-CoV-2 spike protein. During the study period, 17 patients were vaccinated against SARS-CoV-2, with no severe vaccine-related adverse effects. Although median anti-S titers following vaccination or infection were lower in patients receiving immunoglobulin replacement therapy (IGRT) (349 IU/dL) than in those not receiving IGRT (2594 IU/dL; P = .15); 3 of 9 patients on IGRT developed titers >2000 IU/dL. All patients tested negative for autoantibodies against IFN-α, IFN-ß, and IFN-ω at baseline. Most patients with CTLA-4 insufficiency and COVID-19 had nonsevere disease, lacked autoantibodies against type 1 IFNs, and tolerated messenger RNA vaccines with few adverse effects. Whether our findings can be extrapolated to patients receiving CTLA-4-targeting checkpoint inhibitors requires further studies.

Standardizing Opioids Prescribed at Discharge in Trauma Surgery.

INTRODUCTION: Excessive opioid use after sustaining trauma has contributed to the opioid epidemic. Standardizing the quantity of opioids prescribed at discharge can improve prescribing behavior. We hypothesized that adopting new electronic medical record order sets would be associated with decreased morphine milligram equivalents (MME) prescribed at discharge for trauma patients. METHODS: This was a quasi-experimental study examining opioid prescribing practices at a Level 1 Trauma Center. All patients ages 18-89 admitted to the Trauma Service from January 2017 through March 2021 and hospitalized for at least 2 d were included. In November 2020, new trauma admission and discharge order sets were implemented with recommended discharge opioid quantity based on inpatient opioid usage the day prior to discharge multiplied by five. Postintervention prescribing practices were compared to historical controls. The primary outcome was MME at discharge. RESULTS: Baseline characteristics between preintervention and postintervention cohorts were comparable. There was a significant reduction in median MME prescribed at discharge postintervention (112.5 versus 75.0, P < 0.0001). Median inpatient MME usage also significantly reduced postintervention (184.1 versus 160.5; P < 0.0001). There were trends toward increased ideal prescribing per order set recommendation and a reduction in overprescribing. Patients receiving the recommended opioid quantity at discharge had the lowest opioid refill prescription rate (under: 29.6%, ideal: 7.3%, over: 19.7%, P < 0.0001). CONCLUSIONS: For trauma patients requiring inpatient opioid therapy, a pragmatic and individualized intervention was associated with a reduced quantity of discharge opioids without negative outcomes. Reduction in inpatient opioid use was also associated with standardizing prescribing practices of surgeons with electronic medical record order sets.

Multiomics integration of 22 immune-mediated monogenic diseases reveals an emergent axis of human immune health.

Monogenic diseases are often studied in isolation due to their rarity. Here we utilize multiomics to assess 22 monogenic immune-mediated conditions with age- and sex-matched healthy controls. Despite clearly detectable disease-specific and "pan-disease" signatures, individuals possess stable personal immune states over time. Temporally stable differences among subjects tend to dominate over differences attributable to disease conditions or medication use. Unsupervised principal variation analysis of personal immune states and machine learning classification distinguishing between healthy controls and patients converge to a metric of immune health (IHM). The IHM discriminates healthy from multiple polygenic autoimmune and inflammatory disease states in independent cohorts, marks healthy aging, and is a pre-vaccination predictor of antibody responses to influenza vaccination in the elderly. We identified easy-to-measure circulating protein biomarker surrogates of the IHM that capture immune health variations beyond age. Our work provides a conceptual framework and biomarkers for defining and measuring human immune health.

A transient role of the ciliary gene Inpp5e in controlling direct versus indirect neurogenesis in cortical development.

During the development of the cerebral cortex, neurons are generated directly from radial glial cells or indirectly via basal progenitors. The balance between these division modes determines the number and types of neurons formed in the cortex thereby affecting cortical functioning. Here, we investigate the role of primary cilia in controlling the decision between forming neurons directly or indirectly. We show that a mutation in the ciliary gene Inpp5e leads to a transient increase in direct neurogenesis and subsequently to an overproduction of layer V neurons in newborn mice. Loss of Inpp5e also affects ciliary structure coinciding with reduced Gli3 repressor levels. Genetically restoring Gli3 repressor rescues the decreased indirect neurogenesis in Inpp5e mutants. Overall, our analyses reveal how primary cilia determine neuronal subtype composition of the cortex by controlling direct versus indirect neurogenesis. These findings have implications for understanding cortical malformations in ciliopathies with INPP5E mutations.

Glucocorticoid-induced eosinopenia results from CXCR4-dependent bone marrow migration.

Glucocorticoids are considered first-line therapy in a variety of eosinophilic disorders. They lead to a transient, profound decrease in circulating human eosinophils within hours of administration. The phenomenon of glucocorticoid-induced eosinopenia has been the basis for the use of glucocorticoids in eosinophilic disorders, and it has intrigued clinicians for 7 decades, yet its mechanism remains unexplained. To investigate, we first studied the response of circulating eosinophils to in vivo glucocorticoid administration in 3 species and found that the response in rhesus macaques, but not in mice, closely resembled that in humans. We then developed an isolation technique to purify rhesus macaque eosinophils from peripheral blood and performed live tracking of zirconium-89-oxine-labeled eosinophils by serial positron emission tomography/computed tomography imaging, before and after administration of glucocorticoids. Glucocorticoids induced rapid bone marrow homing of eosinophils. The kinetics of glucocorticoid-induced eosinopenia and bone marrow migration were consistent with those of the induction of the glucocorticoid-responsive chemokine receptor CXCR4, and selective blockade of CXCR4 reduced or eliminated the early glucocorticoid-induced reduction in blood eosinophils. Our results indicate that glucocorticoid-induced eosinopenia results from CXCR4-dependent migration of eosinophils to the bone marrow. These findings provide insight into the mechanism of action of glucocorticoids in eosinophilic disorders, with implications for the study of glucocorticoid resistance and the development of more targeted therapies. The human study was registered at ClinicalTrials.gov as #NCT02798523.

Sex differences in neutrophil biology modulate response to type I interferons and immunometabolism.

Differences between female and male immunity may contribute to variations in response to infections and predisposition to autoimmunity. We previously reported that neutrophils from reproductive-age males are more immature and less activated than their female counterparts. To further characterize the mechanisms that drive differential neutrophil phenotypes, we performed RNA sequencing on circulating neutrophils from healthy adult females and males. Female neutrophils displayed significant up-regulation of type I IFN (IFN)-stimulated genes (ISGs). Single-cell RNA-sequencing analysis indicated that these differences are neutrophil specific, driven by a distinct neutrophil subset and related to maturation status. Neutrophil hyperresponsiveness to type I IFNs promoted enhanced responses to Toll-like receptor agonists. Neutrophils from young adult males had significantly increased mitochondrial metabolism compared to those from females and this was modulated by estradiol. Assessment of ISGs and neutrophil maturation genes in Klinefelter syndrome (47, XXY) males and in prepubescent children supported that differences in neutrophil phenotype between adult male and female neutrophils are hormonally driven and not explained by X chromosome gene dosage. Our results indicate that there are distinct sex differences in neutrophil biology related to responses to type I IFNs, immunometabolism, and maturation status that may have prominent functional and pathogenic implications.

Morphometric Differences in the Recurrent Laryngeal Nerve in Patients with Vocal Fold Paralysis.

OBJECTIVES: Injury to the recurrent laryngeal nerve (RLN), if severe enough, can result in vocal fold paralysis. Reinnervation surgery can improve patient outcomes, but previous studies have reported a negative correlation between time since onset of paralysis and surgical outcomes. The ability of the paralyzed nerve to serve as a conduit for donor nerve fibers may be a factor in the success of reinnervation; however, changes in RLN composition after paralysis have not been well studied. Therefore, we investigated the morphometric composition of explanted RLN sections from patients who had experienced vocal fold paralysis for varying length of times. METHODS: Nine nerve sections from unilateral vocal fold paralysis (UVP) patients and seven control nerve sections were analyzed for morphometric parameters including fascicular area, fiber count, fiber density, fiber packing, mean g-ratio, and fiber diameter distribution. Nerves from UVP patients were also compared as a function of time since UVP onset. RESULTS: In comparison to control nerves, paralyzed nerves were found to have significantly lower fiber densities and fiber packing, higher mean g-ratio values, and a shift in diameter distributions toward smaller diameter fibers. With respect to paralysis duration, no significant differences were observed except in fiber diameter distributions, where those with paralysis for >2 years had distributions that were significantly shifted toward smaller diameter fibers. CONCLUSIONS: The morphometric data presented here suggest that correlations between the time since onset of vocal fold paralysis and reinnervation outcomes may be due to fiber size changes in the paralyzed nerve over time.

The two faces of intentional self-inflicted injury: High in-hospital mortality, low postdischarge mortality, but high readmission rates.

BACKGROUND: Intentional self-inflicted injuries present unique challenges in treatment and prevention. We hypothesized intentional self-inflicted injuries would have higher in-hospital and postdischarge mortality than nonintentional self-inflicted injuries trauma. METHODS: Adult patients evaluated 2008 to 2012 were identified in our trauma registry and matched with mortality data from the National Death Index. Intentional self-inflicted injuries were identified using E-Codes. Readmissions were identified and analyzed. Intentional self-inflicted injuries patients who died in-hospital were compared with those surviving to discharge. Univariate analysis was performed using nonparametric tests. Kaplan-Meier curves were plotted to compare mortality ≤5 years postdischarge between intentional self-inflicted injuries and non-intentional self-inflicted injuries patients. RESULTS: In the study, 8,716 patient records were evaluated with 245 (2.8%) classified as intentional self-inflicted injuries. Eighteen (7.8%) patients with intentional self-inflicted injuries had multiple admissions, compared with 352 (4.4%) patients with nonintentional self-inflicted injuries with readmissions (P = .0210). In-hospital mortality was higher for intentional self-inflicted injuries compared with patients with non-intentional self-inflicted injuries (18.7% vs 4.9%, P < .0001). Survival analysis demonstrated that patients with intentional self-inflicted injuries had significantly lower postdischarge mortality at multiple time points. CONCLUSION: Patients with intentional self-inflicted injuries trauma have high in-hospital mortality, but low postdischarge mortality. We attribute this to high lethality mechanisms but appropriate psychiatric treatment and rehabilitation. However, the high intentional self-inflicted injuries readmission rate indicates further study of intentional self-inflicted injuries follow-up is warranted. Better prevention strategies are needed to identify and intervene in patients at-risk for intentional self-inflicted injuries.

Immune regulation by glucocorticoids can be linked to cell type-dependent transcriptional responses.

Glucocorticoids remain the most widely used immunosuppressive and anti-inflammatory drugs, yet substantial gaps exist in our understanding of glucocorticoid-mediated immunoregulation. To address this, we generated a pathway-level map of the transcriptional effects of glucocorticoids on nine primary human cell types. This analysis revealed that the response to glucocorticoids is highly cell type dependent, in terms of the individual genes and pathways affected, as well as the magnitude and direction of transcriptional regulation. Based on these data and given their importance in autoimmunity, we conducted functional studies with B cells. We found that glucocorticoids impair upstream B cell receptor and Toll-like receptor 7 signaling, reduce transcriptional output from the three immunoglobulin loci, and promote significant up-regulation of the genes encoding the immunomodulatory cytokine IL-10 and the terminal-differentiation factor BLIMP-1. These findings provide new mechanistic understanding of glucocorticoid action and emphasize the multifactorial, cell-specific effects of these drugs, with potential implications for designing more selective immunoregulatory therapies.

Association between pre- and intraorbital soft tissue volumes and the risk of orbital blowout fractures using CT-based volumetric measurements.

Orbital blowout fractures result from trauma which breaks the bony orbital wall while sparing the rim. Previous research into fracture mechanism has focused on bony anatomy. This study evaluates the role of preorbital and intraorbital soft tissue volume in fracture risk. A retrospective case-control study was conducted on 51 cases of adults with unilateral orbital blowout fracture, matched to 51 controls who had experienced orbital trauma by comparable mechanisms without sustaining a fracture. Axial Computed Tomography (CT) images with orbital fine cuts were assessed on a 3D post-processing workstation to measure the volume of the pre- and intraorbital soft tissues, then compared between the two groups using Mann-Whitney U analysis. In the case group, there were 40 males (78%), injured by assault (66%), fall (12%), motor vehicle collision (10%), or other cause (12%). The control group included 33 males (65%), injured by assault (55%), fall (22%), motor vehicle (4%), or other cause (20%). There was no significant difference in mechanism rates between case and control groups. Median preorbital volumes were 12.5 cm3 in the case group and14.1 cm3 in controls (p = 0.02). Median intraorbital volumes were 24.4 cm3 in the case group and 25.9 cm3 in controls (p = 0.003). CT volumetric analysis shows that patients who sustained blowout fractures have lower preorbital and intraorbital soft tissue volume than those who did not fracture. This underscores the significant role that soft tissues play in dissipating impact forces, both anterior to the orbital rim and within the orbit itself.

Transcript- and protein-level analyses of the response of human eosinophils to glucocorticoids.

Glucocorticoids are first-line agents for the treatment of many eosinophil-associated disorders; however, their effects on human eosinophils remain poorly understood. To gain an unbiased, genome-wide view of the early transcriptional effects of glucocorticoids on human eosinophils in vivo, RNA sequencing was performed on purified blood eosinophils obtained before and 30, 60, and 120 minutes after administration of a single dose of oral prednisone (1 mg/kg) to three unrelated healthy subjects with hypereosinophilia of unknown significance. The resulting dataset is of high quality and suitable for differential expression analysis. Flow cytometry and qPCR were then performed on three additional cohorts of human subjects, to validate the key findings at the transcript and protein levels. The resulting datasets provide a resource for understanding the response of circulating human eosinophils to glucocorticoid administration.

Gotta catch'em all! Pokémon GO and physical activity among young adults: difference in differences study.

OBJECTIVE:  To estimate the effect of playing Pokémon GO on the number of steps taken daily up to six weeks after installation of the game. DESIGN:  Cohort study using online survey data. PARTICIPANTS:  Survey participants of Amazon Mechanical Turk (n=1182) residing in the United States, aged 18 to 35 years and using iPhone 6 series smartphones. MAIN OUTCOME MEASURES:  Number of daily steps taken each of the four weeks before and six weeks after installation of Pokémon GO, automatically recorded in the "Health" application of the iPhone 6 series smartphones and reported by the participants. A difference in difference regression model was used to estimate the change in daily steps in players of Pokémon GO compared with non-players. RESULTS:  560 (47.4%) of the survey participants reported playing Pokémon GO and walked on average 4256 steps (SD 2697) each day in the four weeks before installation of the game. The difference in difference analysis showed that the daily average steps for Pokémon GO players during the first week of installation increased by 955 additional steps (95% confidence interval 697 to 1213), and then this increase gradually attenuated over the subsequent five weeks. By the sixth week after installation, the number of daily steps had gone back to pre-installation levels. No significant effect modification of Pokémon GO was found by sex, age, race group, bodyweight status, urbanity, or walkability of the area of residence. CONCLUSIONS:  Pokémon GO was associated with an increase in the daily number of steps after installation of the game. The association was, however, moderate and no longer observed after six weeks.

2-O Heparan Sulfate Sulfation by Hs2st Is Required for Erk/Mapk Signalling Activation at the Mid-Gestational Mouse Telencephalic Midline.

Heparan sulfate (HS) is a linear carbohydrate composed of polymerized uronate-glucosamine disaccharide units that decorates cell surface and secreted glycoproteins in the extracellular matrix. In mammals HS is subjected to differential sulfation by fifteen different heparan sulfotransferase (HST) enzymes of which Hs2st uniquely catalyzes the sulfation of the 2-O position of the uronate in HS. HS sulfation is postulated to be important for regulation of signaling pathways by facilitating the interaction of HS with signaling proteins including those of the Fibroblast Growth Factor (Fgf) family which signal through phosphorylation of extracellular signal-regulated kinases Erk1/2. In the developing mouse telencephalon Fgf2 signaling regulates proliferation and neurogenesis. Loss of Hs2st function phenocopies the thinned cerebral cortex of mutant mice in which Fgf2 or Erk1/2 function are abrogated, suggesting the hypothesis that 2-O-sulfated HS structures play a specific role in Fgf2/Erk signaling pathway in this context in vivo. This study investigated the molecular role of 2-O sulfation in Fgf2/Erk signaling in the developing telencephalic midline midway through mouse embryogenesis at E12.5. We examined the expression of Hs2st, Fgf2, and Erk1/2 activity in wild-type and Hs2st-/- mice. We found that Hs2st is expressed at high levels at the midline correlating with high levels of Erk1/2 activation and Erk1/2 activation was drastically reduced in the Hs2st-/- mutant at the rostral telencephalic midline. We also found that 2-O sulfation is specifically required for the binding of Fgf2 protein to Fgfr1, its major cell-surface receptor at the rostral telencephalic midline. We conclude that 2-O sulfated HS structures generated by Hs2st are needed to form productive signaling complexes between HS, Fgf2 and Fgfr1 that activate Erk1/2 at the midline. Overall, our data suggest the interesting possibility that differential expression of Hs2st targets the rostral telencephalic midline for high levels of Erk signaling by increasing the sensitivity of cells to an Fgf2 signal that is rather more widespread.

The native-invasive balance: implications for nutrient cycling in ecosystems.

We conducted single- and mixed-litter experiments in a hardwood forest in Long Island, New York, using leaf litter from phylogenetically paired native and invasive species. We selected long-established, abundant invasive species with wide-ranging distributions in the eastern United States that likely make substantial contributions to the litter pool of invaded areas. Overall, leaf litter from invasive species differed from native litter, though differences varied by phylogenetic grouping. Invasive litter had lower carbon:nitrogen ratios (30.9 ± 1.96 SE vs. 32.8 ± 1.36, P = 0.034) and invasive species lost 0.03 ± 0.007 g of nitrogen and had 23.4 ± 4.9 % of their starting mass remaining at the end of 1 year compared with a loss of 0.02 ± 0.003 g nitrogen and 31.1 ± 2.6 % mass remaining for native species. Mixing litter from two species did not alter decomposition rates when native species were mixed with other native species, or when invasive species were mixed with other invasive species. However, mixing litter of native and invasive species resulted in significantly less mass and nitrogen loss than was seen in unmixed invasive litter. Mixtures of native and invasive litter lost all but 47 ± 2.2 % of initial mass, compared to 37 ± 5.8 % for invasive litter and 50 ± 5.1 % for native litter. This non-additive effect of mixing native and invasive litter suggests that an additive model of metabolic characteristics may not suffice for predicting invasion impacts in a community context, particularly as invasion proceeds over time. Because the more rapid decomposition of invasive litter tends to slow to rates typical of native species when native and invasive litters are mixed together, there may be little impact of invasive species on nutrient cycling early in an invasion, when native leaf litter is abundant (providing litter deposition is the dominant control on nutrient cycling).

Humoral and cellular immunity to primary H1N1 infection in patients with hematologic malignancies following stem cell transplantation.

Limited data are available on immunologic responses to primary H1N1 infection in patients with hematologic malignancies. We present a prospective, case-surveillance study of such patients with real-time polymerase chain reaction (RT-PCR) confirmed H1N1-influenza who presented to our institution between September 2009 and January 2010. Ninety-two patients presented with influenza-like symptoms, and 13 had H1N1 infection confirmed by RT-PCR, including 4 allogeneic stem cell transplant recipients (1 with acute myelogenous leukemia, 1 with chronic lymphoblastic leukemia [CLL], 1 with non-Hodgkin lymphoma, and 1 with chronic myelogenous leukemia), 5 patients with multiple myeloma following autologous stem cell transplantation, 1 patient with multiple myeloma perimobilization, 2 patients with NHL post chemotherapy, and 1 patient with CLL. All 13 patients required hospitalization. Six (43%) were admitted to the intensive care unit (ICU), of whom 4 (67%) died. We evaluated B cell and T cell responses to H1N1 infection prospectively in these patients compared with those in 4 otherwise healthy controls. Within 12 weeks of diagnosis, only 6 of 11 patients developed seropositive antibody titers as measured by hemagglutination-inhibition or microneutralization assays, compared with 4 of 4 controls. H1N1-specific T cells were detected in only 2 of 8 evaluable patients compared with 4 of 4 controls. H1N1-specific T cells were functional, capable of producing interferon γ, tumor necrosis factor α, and CD107a mobilization. Furthermore, CD154 was up-regulated on CD4(+) T cells in 3 of 4 controls and 2 of 2 patients who had both B cell and T cell responses to H1N1. Post-H1N1 infection, 5 of 8 patients developed seasonal influenza-specific T cells, suggesting cross-reactivity induced by H1N1 infection. These data offer novel insights into humoral and cell-mediated immunologic responses to primary H1N1 infection.

Repeated vaccination is required to optimize seroprotection against H1N1 in the immunocompromised host.

BACKGROUND: In 2009 the declaration by the World Health Organization of a global pandemic of influenza-H1N1 virus led to a vaccination campaign to ensure protection for immunocompromised patients. The goal of this study was to determine the efficacy of the 2009 H1N1 vaccine in patients with hematologic malignancies. DESIGN AND METHODS: We evaluated humoral and cellular immune responses to 2009 H1N1 vaccine in 97 adults with hematologic malignancies and compared these responses with those in 25 adult controls. Patients received two injections of vaccine 21 days apart and the controls received one dose. Antibody titers were measured using a hemagglutination-inhibition assay on days 0, 21 and 49 after injection of the first dose. Cellular immune responses to H1N1 were determined on days 0 and 49. RESULTS: By day 21 post-vaccination, protective antibody titers of 1:32 or more were seen in 100% of controls compared to 39% of patients with B-cell malignancies (P<0.001), 46% of allogeneic stem cell transplant recipients (P<0.001) and 85% of patients with chronic myeloid leukemia (P=0.086). After a second dose, seroprotection rates increased to 68%, (P=0.008), 73%, (P=0.031), and 95% (P=0.5) in patients with B-cell malignancies, after allogeneic stem cell transplantation and with chronic myeloid leukemia, respectively. On the other hand, T-cell responses to H1N1 vaccine were not significantly different between patients and controls. CONCLUSIONS: These data demonstrate the efficacy of H1N1 vaccine in most patients with hematologic malignancies and support the recommendation for the administration of two doses of vaccine in immunocompromised patients. These results may contribute towards the development of evidence-based guidelines for influenza vaccination in such patients in the future.

The effect of pilates exercise on trunk and postural stability and throwing velocity in college baseball pitchers: single subject design.

BACKGROUND: Baseball pitchers need trunk strength to maximize performance. The Pilates method of exercise is gaining popularity throughout the country as a fitness and rehabilitation method of exercise. However, very few studies exist that examine the effects of the Pilates method of exercise on trunk strength or performance. OBJECTIVES: Using a single subject, multiple baseline across subjects design, this study examines the effects of the Pilates method of exercise on performance of double leg lowering, star excursion balance test, and throwing velocity in college-aged baseball pitchers. METHODS: A convenience sample of three college baseball pitchers served as the subjects for this single subject design study. For each subject, double leg lowering, star excursion balance test, and throwing speed were measured prior to the introduction of the intervention. When baseline test values showed consistent performance, the intervention was introduced to one subject at a time. Intervention was introduced to the other subjects over a period of 4 weeks as they also demonstrated consistent performance on the baseline tests. Intervention was continued with periodic tests for the remainder of the 10 week trial. RESULTS: Each subject improved in performance on double leg lowering (increased 24.43-32.7%) and star excursion balance test (increased 4.63-17.84%) after introduction of the intervention. Throwing speed improved in two of the three subjects (up to 5.61%). DISCUSSION AND CONCLUSIONS: The Pilates method of exercise may contribute to improved performance in double leg lowering, star excursion balance tests, and throwing speed in college baseball pitchers.

Biodiversity as a barrier to ecological invasion.

Biological invasions are a pervasive and costly environmental problem that has been the focus of intense management and research activities over the past half century. Yet accurate predictions of community susceptibility to invasion remain elusive. The diversity resistance hypothesis, which argues that diverse communities are highly competitive and readily resist invasion, is supported by both theory and experimental studies conducted at small spatial scales. However, there is also convincing evidence that the relationship between the diversity of native and invading species is positive when measured at regional scales. Although this latter relationship may arise from extrinsic factors, such as resource heterogeneity, that covary with diversity of native and invading species at large scales, the mechanisms conferring greater invasion resistance to diverse communities at local scales remain unknown. Using neighbourhood analyses, a technique from plant competition studies, we show here that species diversity in small experimental grassland plots enhances invasion resistance by increasing crowding and species richness in localized plant neighbourhoods. Both the establishment (number of invaders) and success (proportion of invaders that are large) of invading plants are reduced. These results suggest that local biodiversity represents an important line of defence against the spread of invaders.