Sex differences in musculoskeletal injury epidemiology and subsequent loss of tactical readiness during Marine Corps Officer Candidates School.

INTRODUCTION: The US Marine Corps (USMC) Officer Candidates School (OCS) is a 10-week training course for Marine Officer Candidates (MOCs). OCS training is rigorous and demanding, which results in a high risk of musculoskeletal injuries (MSIs). The objective of this analysis was to describe MSIs among women and men during the USMC OCS at Quantico, Virginia, from September 2020 to November 2021. METHODS: This prospective cohort study assessed MSIs that occurred among 736 MOCs (women: 17.8% of sample, men: 82.2%). Data for the study were derived from routinely collected injury data by athletic trainers and physical therapists embedded within the training units. Injury incidence, event at the time of injury occurrence, anatomic location, injury type and disposition following injury were described. Fisher's exact tests were used to compare proportions of injured women and men. RESULTS: The cumulative injury incidence was higher among women (39.7%) compared with men (23.1%, p<0.001). When specific events associated with injuries were reported, most frequent events were the obstacle course (women: 20.9% of injuries, men: 12.9%) and the conditioning hike (women: 11.6%, men: 6.9%). Most injures affected the lower body (women: 67.4%, men: 70.8%). The most frequent body part injured was the lower leg (18.6%) in women and the knee (23.3%) in men. The most frequent injury type was strain (women: 39.5%, men: 24.3%), followed by sprain (women: 16.3%, men: 14.9%). A greater percentage of female (92.3%) compared with male MOCs (69.3%; p<0.001) were assigned light duty status following MSIs. CONCLUSIONS: Mitigation of injuries during OCS events such as the obstacle course and the conditioning hike needs further investigation. The high risk of overuse lower leg injuries among women and the higher incidence of injuries among women compared with men underscore the need for further investigation of modifiable sex-specific injury risk factors.

[Research status of the innervation of prostate cancer and its potential clinical applications for nerve-targeted therapy].

Nerve fibers are important component in tumor microenvironment (TME) and have been shown to promote the early development of the prostate cancer and metastasis of advanced prostate cancer. Besides, it also activates an angio-metabolic switch, altering the endothelial cell metabolism to trigger angiogenesis. Most studies have showed that nerve infiltration in prostate cancer may be regulated by a variety of nerve growth factors secreted by cancer cells.However, surprisingly, neurons in the TME could also be neural progenitors originating from the subventricular zone. Recently, the effects of tumor-associated neuro-immune signal dysfunction on cancer promotion has gradually become a new focus. Therefore, elucidating the molecular and cellular mechanisms of nerve and its signaling in prostate cancer will help improve the value of clinical application of nerve targeted therapy.

An in vivo model of postinflammatory hyperpigmentation and erythema: clinical, colorimetric and molecular characteristics.

BACKGROUND: Postinflammatory hyperpigmentation (PIH) is a common, acquired pigmentary disorder of the skin associated with significant quality-of-life impairment, especially in individuals with skin of colour. Current treatment for PIH is limited, largely due to a poor understanding of disease pathogenesis and the lack of a representative disease model. OBJECTIVES: This study is intended to further develop, update and validate our previously designed in vivo model of acne-induced PIH/postinflammatory erythema (PIE) using different concentrations of trichloroacetic acid (TCA), a medium-depth chemical peel. METHODS: Twenty-nine patients with skin types II-VI and clinician-confirmed presence of two or more truncal acne pustules and PIH/PIE were included. On the basis of Investigator's Global Assessment (IGA), clinical polarized photography (CPP), colorimetry and Skindex, we experimentally determined an optimum TCA concentration and assessed our model's ability to exhibit a dose-response relationship between degree of inciting insult and severity of resulting pigmentation. We also performed differential microRNA profiling and pathway analysis to explore the potential of microRNAs as molecular adjuncts to our model. RESULTS: Application of TCA 30% produced lesions indistinguishable from acne-induced PIH and PIE lesions on the basis of colorimetry data without causing epidermal necrosis. Application of progressively increasing TCA doses from 20% to 30% resulted in concentration-dependent increases in CPP, IGA and colorimetry scores at all timepoints during the study. miRNA-31 and miRNA-23b may play a role in PIH pathogenesis, although further validation is required. CONCLUSIONS: Our TCA-based in vivo model, using TCA concentrations between 20% and 30% with an optimum of 30%, enables the quantitative assessment of the pigmentary response to varying degrees of cutaneous inflammation in a fashion that mirrors natural acne-induced PIH and PIE.

[Clinical analysis of 60 children with anaplastic large cell lymphoma in a single center].

Objective: To summarize the clinical features, treatment outcome and prognostic factors of childhood anaplastic large cell lymphoma (ALCL). Methods: Clinical data of 60 newly diagnosed and biopsy-proven ALCL pediatric patients (≤18 years of age) at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine from January 2010 to December 2018 were collected. All patients were treated with the Chinese Children Cancer Group-B cell-non-Hodgkin Lymphoma 2010 (CCCG-BNHL-2010) regimen. Overall survival (OS), event free survival (EFS) and progression free survival (PFS) rates were calculated by the Kaplan-Meier method. Univariate analysis was performed with Log-Rank test to find factors of poor prognosis. Results: Among 60 ALCL patients included in the current study, 39 were males and 21 females, the age of onset was 7.9 (1.2-16.7) years. Among all cases, 43 (72%) had B syndrome (any of the following: fever, drenching, weight loss). Forty-nine (82%) cases had lactate dehydrogenase (LDH) levels<2 times upper limit of normal (ULN) and 11 (18%) cases had LDH levels 2-<4 times ULN. The distribution of stages was stage Ⅰ,Ⅱ,Ⅲ, and Ⅳ in 2% (1/60), 5% (3/60), 92% (55/60), and 2% (1/60) of patients, respectively. Of 58 cases who had results of anaplastic lymphoma kinase (ALK) immunohistochemical staining, 53 (91%, 53/58) cases were positive. Visceral involvement was observed in 12 patients (20%). The 4-year OS and EFS rates were (88±4)% and (76±6)% for the entire group, respectively. Univariate analysis for gender, B symptoms, LDH level, ALK expression, clinical stage and visceral involvement showed that only LDH level correlated with an inferior OS rate (χ²=6.571, P=0.010) while not correlated with EFS rate. No independent risk factor for disease progression or recurrence was found by Logistic regression. Up to the last follow-up, 44 cases were continuously at complete remission state, and their follow-up time was 50 (13-119) months. Of 13 (23%) cases experienced disease progression or relapse, 3 cases abandoned treatment, 2 cases progressed to death, 8 cases received second line or salvage treatment (6 survived at last follow-up). For post progression or relapse cases, the 2-year OS and PFS rates were (60±16)% and (16±14)%, respectively. The treatment related death occurred in 3 cases (5%) and all of them were due to severe infection during the chemotherapy. Conclusions: The efficacy of CCCG-BNHL-2010 regimen in the treatment of children with ALCL was good. However, the safety needs to be improved as the treatment-related mortality in the present study was slightly higher. Efficient second line or salvage treatment can achieve cure in pediatric patients post progression or recurrence. LDH ≥2 times ULN was associated with worse prognosis.

[Progress of researches on global prevalence of Blastocystis hominis human infections and its subtypes].

Blastocystis hominis is a parasite that parasitizes in the intestines of humans and animals, and is closely related to a variety of gastrointestinal diseases such as abdominal pain and diarrhea. B. hominis is distributed worldwide, and the prevalence of B. hominis infections and dominant subgenotypes vary in countries and in regions from the same country. This paper reviews the global prevalence of B. hominis human infections, its subtypes and geographical distribution, so as to provide insights into the understanding of the global epidemiology of B. hominis and the management of B. hominis infections.

Using Machine Learning to Predict Lower-Extremity Injury in US Special Forces.

INTRODUCTION: Musculoskeletal injury rates in military personnel remain unacceptably high. Application of machine learning algorithms could be useful in multivariate models to predict injury in this population. The purpose of this study was to investigate if interaction between individual predictors, using a decision tree model, could be used to develop a population-specific algorithm of lower-extremity injury (LEI) risk. METHODS: One hundred forty Air Force Special Forces Operators (27.4 ± 5.0 yr, 177.6 ± 5.8 cm, 83.8 ± 8.4 kg) volunteered for this prospective cohort study. Baseline testing included body composition, isokinetic strength, flexibility, aerobic/anaerobic capacity, anaerobic power, and landing biomechanics. To evaluate unilateral landing patterns, subjects jumped off two-feet from a distance (40% of their height) over a hurdle and landing single-legged on a force plate. Medical chart reviews were conducted 365 d postbaseline. χ automatic interaction detection (CHAID) was used, which compares predictor variables to LEI and assigns a population-specific "cut-point" for the most relevant predictors. RESULTS: Twenty-seven percent of operators (n = 38) suffered LEI. A maximum knee flexion angle difference of 25.1% had the highest association with injury in this population (P = 0.006). Operators with >25.1% differences in max knee flexion angle (n = 13) suffered LEI at a 69.2% rate. Seven of the 13 Operators with >25.1% difference in max knee flexion angle weighed >81.8 kg, and 100% of those operators suffered LEI (P = 0.047; n = 7). Only 33% of operators with >25.1% difference in max knee flexion angle that weighed <81.8 kg suffered LEI. CONCLUSIONS: This study demonstrated increased risk of LEI over a 365-d period in Operators with greater differences in single-leg landing strategies and higher body mass. The CHAID approach can be a powerful tool to analyze population-specific risk factors for injury, along with how those factors may interact to enhance risk.

Shared Neuromuscular Performance Traits in Military Personnel with Prior Concussion.

Concussions are common in military personnel and may result in increased risk of musculoskeletal injury. One plausible explanation for this risk could be that neuromotor deficiencies enhance injury risk after a concussion through altered muscular activation/contraction timing. PURPOSE: To compare military personnel with at least one concussion during the past 1 month to 2 yr (CONCUSSED) to military branch-matched, age-matched, and Special Operations Forces group-matched controls (CONTROL) on physiological, musculoskeletal, and biomechanical performance. METHODS: A total of 48 (24 CONCUSSED, 24 CONTROL) male Air Force and Naval Special Warfare Operators age 19 to 34 yr participated in the study. Participants self-reported demographics/injury history and completed the following assessments: 1) physiological-body composition, anaerobic power and capacity, aerobic capacity and lactate threshold; 2) musculoskeletal-lower extremity isokinetic strength testing, including time to peak torque; and 3) biomechanical-single-leg jump and landing task, including landing kinematics of the hip, knee and ankle. A machine learning decision tree algorithm (C5.0) and one-way ANOVA were used to compare the two groups on these outcomes. RESULTS: Despite nonsignificant differences using ANOVA, the C5.0 algorithm revealed CONCUSSED demonstrated quicker time to peak knee flexion angle during the single-leg landing task (≤0.170 s; CONCUSSED: n = 22 vs CONTROL: n = 14), longer time to peak torque in knee extension isokinetic strength testing (>500 ms; CONCUSSED: n = 18 vs CONTROL: n = 4) and larger knee flexion angle at initial contact (>7.7°; CONCUSSED: n = 18 vs CONTROL: n = 2). CONCLUSION: The findings supported the hypothesis that CONCUSSED military personnel would demonstrate altered neuromuscular control in landing strategies and muscular activation. Future research should assess prospectively neuromuscular changes after a concussion and determine if these changes increase risk of subsequent musculoskeletal injuries.

Small RNAs Play Big Roles: MicroRNAs in Diabetic Wound Healing.

Skin and corneal wounds in diabetics are a major healthcare burden. MicroRNAs are small, non-coding RNAs that post-transcriptionally regulate the expression of protein-coding genes. Studies have identified microRNAs involved in all phases of wound healing. The dysregulation of microRNAs can contribute to impaired or delayed skin and corneal wound healing in diabetics. Here, we present a comprehensive review of the literature involving microRNAs in diabetic skin and corneal wound healing as well as those serving as potential biomarkers for diabetic wound healing.

TGF-ß1-induced transcription factor networks in Langerhans cell development and maintenance.

Langerhans cells (LC) represent a specialized subset of evolutionarily conserved dendritic cells (DC) that populate stratified epithelial tissues, which are essential for the induction of skin and mucosal immunity and tolerance, including allergy. Transforming growth factor-ß1 (TGF-ß1) has been confirmed to be a predominant factor involved in LC development. Despite great advances in the understanding of LC ontogeny and diverse replenishment patterns, the underlying molecular mechanisms remain elusive. This review focuses on the recent discoveries in TGF-ß1-mediated LC development and maintenance, with special attention to the involved transcription factors and related regulators.

Interleukin-10 does not modulate clopidogrel platelet response in mice.

UNLABELLED: ESSENTIALS: It is unclear whether interleukin-10 (IL-10) could affect clopidogrel metabolism and response. The bioactivation of and response to clopidogrel were determined between mice with or without IL-10. Maximum clopidogrel active metabolite levels were the major driver of platelet response to clopidogrel. IL-10 did not modulate maximum levels of clopidogrel active metabolite and its antiplatelet effects. BACKGROUND: Elevated plasma interleukin-10 (IL-10) levels were observed in patients who responded less to clopidogrel (a prodrug that is required for further metabolic bioactivation in the liver). However, no data are currently available suggesting whether there is such an association. OBJECTIVE: To systematically explore possible differences in the formation of and response to clopidogrel active metabolite (CAM) in mice with or without IL-10 gene expression. METHODS: A single oral dose of clopidogrel (10 mg kg(-1)) was given to IL-10 knockout (KO) mice and wild-type (WT) control mice, respectively, and pharmacokinetic parameters of clopidogrel and CAM were calculated. Moreover, adenosine diphosphate-induced whole-blood platelet aggregation was measured in mice receiving 0, 5, 10, or 20 mg kg(-1) of clopidogrel, respectively. RESULTS: Compared with IL-10 KO mice, WT mice had significantly lower area under the plasma concentration-time curve (AUC) of CAM as a result of a shorter mean elimination half-life but had significantly higher AUC of clopidogrel due to slower systemic clearance and smaller volume of distribution. Although AUC of CAM was significantly lower in WT mice than in KO mice, antiplatelet effects of clopidogrel did not differ significantly between the two mouse groups, as their maximum plasma concentrations (Cmax ) of CAM were not significantly different. CONCLUSIONS: IL-10 expression level affects AUC rather than Cmax of CAM, but the Cmax of CAM is the major driver of antiplatelet effects of clopidogrel in mice.

Modification of N staging systems for penile cancer: a more precise prediction of prognosis.

BACKGROUND: The tumour-node-metastasis (TNM) classification is the most widely used tool for penile cancer. However, the current system is based on few studies and has been unchanged since 2009. We determined whether a modified pathological N staging system that incorporates the laterality and number of lymph node metastases (LNMs) increases the accuracy of the results in predicting survival compared with the 7th edition of the pathological N staging system of the American Joint Committee on Cancer (AJCC) for penile cancer. METHODS: The clinical and histopathologic data from 111 patients with penile cancer with LNMs were analysed. Univariate and multivariate Cox proportional hazard regression analyses were used to determine the impact of the clinical and pathological factors on disease-specific survival of these patients. The predictive accuracy was further assessed using the concordance index. RESULTS: According to the 7th edition of the pathological N classification, the 3-year disease-specific survival (DSS) rates for patients with pN1, pN2, and pN3 disease are 89.6%, 65.9%, and 33.6%, respectively (P(N1-N2)=0.030, P(N2-N3)<0.001, P<0.001). Under the modified pathological N category criteria, the 3-year DSS rates for pN1, pN2, and pN3 patients were 90.7%, 60.5%, and 31.4%, respectively (P(N1-N2)=0.005, P(N2-N3)=0.004, P<0.001). In separate multivariate Cox regression models, only modified N stages (hazard ratio: 4.877, 10.895; P=0.018, P<0.001) exhibited independent effects on the outcome. The accuracy of the modified pathological N category was significantly increased. CONCLUSIONS: The modified pathological N staging system is a better reflection of the prognosis of patients with penile cancer. Our study should contribute to the improvement of prognostic stratification and systemic treatment to avoid overtreatment of patients.

Differential CTLA-4 expression in human CD4+ versus CD8+ T cells is associated with increased NFAT1 and inhibition of CD4+ proliferation.

Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a costimulatory molecule that negatively regulates T-cell activation. Originally identified in murine CD8(+) T cells, it has been found to be rapidly induced on human T cells. Furthermore, CTLA-4 is expressed on regulatory T cells. Clinically, targeting CTLA-4 has clinical utility in the treatment of melanoma. Whether the expression of CTLA-4 is differentially regulated in CD8(+) vs CD4(+) human T cells is unclear. Here, we analyzed CTLA-4 in normal human CD4(+) and CD8(+) T-cell subsets and show for the first time that CTLA-4 is expressed significantly higher in the CD4(+) T cells than in CD8(+) T cells. CTLA-4 is higher at the protein and the transcriptional levels in CD4(+) T cells. This increase is due to the activation of the CTLA-4 promoter, which undergoes acetylation at the proximal promoter. Furthermore, we show that blocking CTLA-4 on CD4(+) T cells permits greater proliferation in CD4(+) vs CD8(+) cells. These findings demonstrate a differential regulation of CTLA-4 on CD4(+) and CD8(+) T-cell subsets, which is likely important to the clinical efficacy for anti-CTLA-4 therapies. The findings hint to strategies to modulate CTLA-4 expression by targeting epigenetic transcription to alter the immune response.

microRNA miR-17-92 cluster is highly expressed in epidermal Langerhans cells but not required for its development.

Langerhans cells (LCs) are bone marrow-derived immature skin-residential dendritic cells (DCs) with a life cycle distinct from that of other types of DCs. The mechanisms involved in LC homeostasis and immunological functions are still not clear. MicroRNAs (miRNAs) are a class of short noncoding RNAs that regulate gene expression through either translational repression or mRNA degradation. A recent study showed that specific deletion of total miRNAs in DCs affects the homeostasis and function of only LCs, but not of other types of DCs. The roles of specific individual miRNA in LC development are still lacking. The miRNA miR-17-92 class, encoding miR-17, miR-18, miR-19a, miR-19b, miR-20 and miR-92, plays a very important role in B- and T-cell development and function. Here, we first report that epidermal LCs highly express the miR-17-92 class compared with spleen naive T cells. To further characterize the role of miR-17-92 in LC development, we generated LC-specific miR-17-92 knockout and knock-in mice. Interestingly, LC-specific gain- and loss-of-function of miR-17-92 cluster did not significantly change LC homeostasis, maturation ability, antigen capture and migration to draining lymph nodes. Thus, the miR-17-92 cluster may be functionally redundant and not critically required for LC development and function.

Serum non-coding RNAs as biomarkers for osteoarthritis progression after ACL injury.

OBJECTIVE: The aim of this study was to examine serum non-coding RNAs as potential biomarkers for cartilage damage associated with anterior cruciate ligament (ACL) injury. METHODS: Serum was obtained from 80 patients 1 year after surgery for ACL injury and 60 normal donors without overt skeletal injury. Total serum RNA was isolated, small non-coding RNAs profiled by TaqMan array MicroRNA (miRNA) analysis and individual small RNA assays performed by quantitative TaqMan RT-PCR (qPCR). Semi-quantitative magnetic resonance imaging (MRI) analysis was performed using Whole Organ Magnetic Resonance Knee Score (WORMS) scoring for analysis of cartilage damage. RESULTS: Initial TaqMan array miRNA profiling showed an increased serum concentration of a small nucleolar RNA (snoRNA), U48, in five patients with cartilage damage compared with that in five patients without cartilage damage and six normal donors. Independent qPCR analysis of snoRNAs in serum from all patients and normal donors showed a strong association between the serum level of another snoRNA, U38, and cartilage damage in ACL injury patients and together with snoRNA, U48, clear distinction between ACL injury patients and normal donors. CONCLUSION: SnoRNAs U38 and U48 are significantly elevated in the serum of patients developing cartilage damage at 1 year after ACL injury. Serum levels of U38 have the potential to facilitate early diagnosis of patients with cartilage damage after ACL injury. This study suggests serum non-coding RNAs may serve as novel noninvasive biomarkers for the detection and assessment of cartilage damage after ACL injury.

Different pathways are involved in arsenic-trioxide-induced cell proliferation and growth inhibition in human keratinocytes.

BACKGROUND: Arsenic is a carcinogen that is associated with an increased risk of human skin cancer. On the other hand, arsenic trioxide (As(2)O(3)) has potential anticancer activity against a wide range of carcinomas. The mechanisms involved in these two opposing processes remain unclear. METHODS: We used normal human keratinocytes (NHK), the human keratinocyte HaCaT cell line and human epidermal carcinoma cells (A431 cell line) to investigate potential pathways involved in the effects on cell proliferation and growth inhibition by different concentrations of As(2)O(3). RESULTS: At low concentrations (0.5-32 nM), As(2)O(3) enhanced keratinocyte proliferation and regulated the expression of about 172 genes. Among them, cell cycling pathway genes (including CDK4 and E2F1) were significantly upregulated. At high concentrations (0.5-10 microM), As(2)O(3) inhibited cell growth in NHK and HaCaT cells, but not in A431 cells. As(2)O(3) significantly induced NHK and HaCaT apoptosis through the activation of caspase-3, as well as cell cycle arrest at the G2-M phase. CONCLUSION: Our data suggest that different pathways are involved in As(2)O(3)-mediated proliferation and growth inhibition. In addition, skin carcinoma cells were resistant to As(2)O(3)-induced cell growth inhibition and apoptosis when compared to NHK and HaCaT cells. Therefore, As(2)O(3) may not be appropriate for treatment of skin carcinomas.

Macharistol, a new cytotoxic cinnamylphenol from the stems of Machaerium aristulatum.

A new cinnamylphenol, macharistol (1), along with a known pterocarpan, (+)-medicarpin (2), were isolated as cytotoxic constituents from the stems of Machaerium aristulatum. In addition, a known pterocarpan, (+)-maackiain (3), and a known isoflavone, formononetin (4), were identified as inactive constituents. Compound 1 was evaluated in the in vivo hollow fiber assay with KB, Col-2, and hTERT-RPE1 cells and found to be inactive at the highest dose (25 mg/kg body weight) tested.

Murine inter-strain polymorphisms alter gene targeting frequencies at the mu opioid receptor locus in embryonic stem cells.

Chromosomal regions near the mu opioid receptor gene are implicated in morphine preference by quantitative trait loci studies. Differences in expression of the mu opioid receptor are expected to contribute to differences in inter-individual (humans) or strain-specific (mice) responses to painful stimuli, opiate drugs, and addictive behaviors. The search for relevant genetic elements is hindered by a lack of inter-strain (or inter-individual) genomic sequence information. This work describes 9.3 kb of DNA sequence surrounding exons 2 and 3 of the murine mu opioid receptor gene from both 129/Sv and C57BL/6 strains. While the exons are perfectly conserved, intronic sequences demonstrate approximately a 2.5% divergence between the strains. Polymorphism within these intronic regions may effect either primary transcript stability or C-terminal splicing. Homologous recombination frequencies of targeting vectors harboring mu opioid receptor gene sequences have also been compared in embryonic stem cells derived from these strains. Non-isogenic targeting reduces homologous recombination in both 129/Sv and C57BL/6 embryonic stem cells by greater than 15-fold. These findings are the first to examine C57BL/6 embryonic stem cells for non-isogenic targeting frequencies and to define polymorphisms that exist between these mouse strains which might contribute to opioid behaviors.

Activation of natural killer T cells by alpha-galactosylceramide treatment prevents the onset and recurrence of autoimmune Type 1 diabetes.

Type 1 diabetes (T1D) in non-obese diabetic (NOD) mice may be favored by immune dysregulation leading to the hyporesponsiveness of regulatory T cells and activation of effector T-helper type 1 (Th1) cells. The immunoregulatory activity of natural killer T (NKT) cells is well documented, and both interleukin (IL)-4 and IL-10 secreted by NKT cells have important roles in mediating this activity. NKT cells are less frequent and display deficient IL-4 responses in both NOD mice and individuals at risk for T1D (ref. 8), and this deficiency may lead to T1D (refs. 1,6-9). Thus, given that NKT cells respond to the alpha-galactosylceramide (alpha-GalCer) glycolipid in a CD1d-restricted manner by secretion of Th2 cytokines, we reasoned that activation of NKT cells by alpha-GalCer might prevent the onset and/or recurrence of T1D. Here we show that alpha-GalCer treatment, even when initiated after the onset of insulitis, protects female NOD mice from T1D and prolongs the survival of pancreatic islets transplanted into newly diabetic NOD mice. In addition, when administered after the onset of insulitis, alpha-GalCer and IL-7 displayed synergistic effects, possibly via the ability of IL-7 to render NKT cells fully responsive to alpha-GalCer. Protection from T1D by alpha-GalCer was associated with the suppression of both T- and B-cell autoimmunity to islet beta cells and with a polarized Th2-like response in spleen and pancreas of these mice. These findings raise the possibility that alpha-GalCer treatment might be used therapeutically to prevent the onset and recurrence of human T1D.