Testicular volume in 268 children and adolescents followed-up for childhood obesity-a retrospective cross-sectional study.

CONTEXT: Prevalence of obesity in childhood has increased over the past few decades. The impact of obesity and of obesity-related metabolic disorders on testicular growth is unknown. OBJECTIVE: To evaluate the impact of obesity, hyperinsulinemia, and insulin resistance on testicular volume (TV) in pre-pubertal (<9 years), peri-pubertal (9-14 years), and post-pubertal (14-16 years) periods. METHODS: We collected data on TV, age, standard deviation score (SDS) of the body mass index (BMI), insulin, and fasting glycemia in 268 children and adolescents followed-up for weight control. RESULTS: Peri-pubertal boys with normal weight had a significantly higher TV compared to those with overweight or obesity. No difference was found in the other age ranges when data were grouped according to BMI. Pre- and post-pubertal children/adolescents with normal insulin levels had significantly higher TV compared to those with hyperinsulinemia. Peri-pubertal boys with hyperinsulinemia had significantly higher TV compared to those with normal insulin levels. Post-pubertal adolescents with insulin resistance had lower TV and peri-pubertal boys had higher TV compared to those without insulin resistance. No difference was found in pre-puberty. CONCLUSIONS: Closer control of the body weight and the associated metabolic alterations in childhood and adolescence may maintain testicular function later in life.

An ISB-consistent Denavit-Hartenberg model of the human upper limb for joint kinematics optimization: validation on synthetic and robot data during a typical rehabilitation gesture.

Several biomedical contexts such as diagnosis, rehabilitation, and ergonomics require an accurate estimate of human upper limbs kinematics. Wearable inertial measurement units (IMU s) represent a suitable solution because of their unobtrusiveness, portability, and low-cost. However, the time-integration of the gyroscope angular velocity leads to an unbounded orientation drift affecting both angular and linear displacements over long observation interval. In this work, a Denavit-Hartenberg model of the upper limb was defined in accordance with the guidelines of the International Society of Biomechanics and exploited to design an optimization kinematics process. This procedure estimated the joint angles by minimizing the difference between the modelled and IMU-driven orientation of upper arm and forearm. In addition, reasonable constraints were added to limit the drift influence on the final joint kinematics accuracy. The validity of the procedure was tested on synthetic and experimental data acquired with a robotic arm over 20 minutes. Average rms errors amounted to 2.8 deg and 1.1 for synthetic and robot data, respectively. Clinical Relevance - The proposed method has the potential to improve robustness and accuracy of multi-joint kinematics estimation in the general contexts of home-based tele-rehabilitation interventions. In this respect adoption of multi-segmental kinematic model along with physiological joint constraints could contribute to address current limitations associated to unsupervised analysis in terms of monitoring and outcome assessment.

A wearable multi-sensor system for real world gait analysis.

Gait analysis is commonly performed in standardized environments, but there is a growing interest in assessing gait also in ecological conditions. In this regard, an important limitation is the lack of an accurate mobile gold standard for validating any wearable system, such as continuous monitoring devices mounted on the trunk or wrist. This study therefore deals with the development and validation of a new wearable multi-sensor-based system for digital gait assessment in free-living conditions. In particular, results obtained from five healthy subjects during lab-based and real-world experiments were presented and discussed. The in-lab validation, which assessed the accuracy and reliability of the proposed system, shows median percentage errors smaller than 2% in the estimation of spatio-temporal parameters. The system also proved to be easy to use, comfortable to wear and robust during the out-of-lab acquisitions, showing its feasibility for free-living applications.

Impact of exclusive e-cigarettes and heated tobacco products use on muco-ciliary clearance.

BACKGROUND: Tobacco smoking impairs mucociliary clearance (MCC) efficiency as shown by prolonged saccharin test transit time (STTT). Avoiding exposure to tobacco smoke from combustible cigarettes may restore MCC function and former smokers have been shown to exhibit similar STTT as never smokers. The impact on STTT of switching from smoking to combustion-free tobacco products such as e-cigarettes (ECs) and heated tobacco products (HTPs) is not known. METHODS: We report STTT of exclusive EC and HTP users. Test results were compared with those obtained in current, former, and never smokers. RESULTS: STTT were obtained from 39 current, 40 former, 40 never smokers, and from 20 EC and 20 HTP users. Comparison of STTT values showed significant difference among the five study groups (p < 0.00001) with current smokers having a median [interquartile range (IQR)] STTT of 13.15 min, which was significantly longer compared with that of all other study groups. In particular, compared with former (7.26 min) and never smokers (7.24 min), exclusive EC users and exclusive HTP users had similar STTT at 7.00 and 8.00 min, respectively. CONCLUSION: Former smokers who have switched to exclusive regular use of combustion-free nicotine delivery systems (i.e., ECs and HTPs) exhibit similar saccharin transit time as never and former smokers. This suggests that combustion-free nicotine delivery technologies are unlikely to have detrimental effects on MCC function.

DoMoMEA: a Home-Based Telerehabilitation System for Stroke Patients.

After a cerebral stroke, survivors need to follow a neurorehabilitation program including exercises to be executed under a therapist's supervision or autonomously. Technological solutions are needed to support the early discharge of the patients just after the primary hospital treatments, by still providing an adequate level of rehabilitation. The DoMoMEA Project proposes a fully-wearable m-health solution able to administer a neurorehabilitation therapy in the patient's home or every other place established by the patient for a rehabilitation session. The exploitation of magneto-inertial measurement units only, wirelessly connected to an Android-operated device, provides robustness to different operating conditions and immunity to optical occlusion problems, compared to RGB-D cameras. Patients' engagement is fostered by the exploitation of the exergame version of the ten rehabilitation exercises, implemented in Unity 3D. Store-and-forward telemonitoring features, supported by cloud-based storage and by a web application accessible from anywhere by medical personnel and patients, enable constant transparent monitoring of the rehabilitation progresses. The clinical trial of the DoMoMEA telerehabilitation system will involve 40 post-stroke patients with mild impairment and will start as soon as the restrictions due to the COVID-19 pandemic will allow to enroll patients.

Monthly fluctuations in 25-hydroxy-vitamin D levels in day and rotating night shift hospital workers.

PURPOSE: Epidemiological studies have suggested that indoor hospital employees, either day or night shift workers, are at high risk of metabolic and cardiovascular diseases. Interestingly, previous reports have also described a higher prevalence of vitamin D (25OHD) deficiency among these workers. However, few studies have determined the monthly variations in 25OHD levels in indoor hospital employees. METHODS: To address this lack of knowledge, in 2018, during the periodic health surveillance checks at the Service of Occupational Medicine, we measured 25OHD levels in a group of indoor hospital workers (88 rotating night shift workers vs 200 day workers). Each participant received a single annual health surveillance check. RESULTS: The mean levels of 25OHD were consistently below the lower limit of the normal range in both groups throughout the year. Only in the summer, day workers but not rotating night shift workers (mean 25.9 ± 11.3 ng/ml vs 23.1 ± 9.1 ng/ml; p = 0.042) showed levels significantly higher than those in the other seasons. This difference remained statistically significant even after correction for study covariates [ß = -  1.649 (CI - 0.283/- 3.482), p = 0.039]. A cosinor analysis confirmed that the difference in the 25OHD levels between groups was present later in the year. CONCLUSIONS: We found that relatively young healthy hospital workers, especially those with rotating night shifts, in the absence of significant metabolic risk factors, have a high risk of 25OHD deficiency/insufficiency. Because 25OHD deficiency may lead to a progression to more severe conditions such as osteoporosis or bone fractures, our results should be verified in larger cohorts including different ancestries.

Dietary inflammatory index and mortality: a cohort longitudinal study in a Mediterranean area.

BACKGROUND: Higher Dietary Inflammatory Index (DII®) scores are associated with increased morbidity and mortality. However, little is known about the effects of DII on mortality in Mediterranean countries. Therefore, in the present study, we aimed to investigate the potential association between DII scores and overall, cancer and cardiovascular disease (CVD) mortality in people living in a Mediterranean area. METHODS: DII scores were calculated using a validated food-frequency questionnaire. DII scores were then categorised into tertiles. Mortality was ascertained via death certificates. The association between DII scores with overall and cause-specific mortality was assessed via a multivariable Cox's regression analysis and reported as hazard ratios (HRs) with their 95% confidence intervals (CIs). RESULTS: The study included 1565 participants (mean age 65.5 years; females 44.7%). After a median follow-up of 12 years (2005-2017), 366 (23.4%) participants died. After adjusting for 17 potential confounders, people with higher DII scores had an increased risk of death compared to those in the lowest (most anti-inflammatory) tertile (HR = 1.38; 95% CI = 1.04-1.82 for the second tertile; HR = 1.38; 95% CI = 1.03-1.86 for the third tertile). Each 1 SD increase in DII score increased the risk of death by 13%. No association was found between DII scores and cancer or CVD death when considered separately. CONCLUSIONS: Higher DII scores were associated with a significantly higher mortality risk, whereas the association with cause-specific mortality was less clear. These findings highlight the potential importance of diet in modulating inflammation and preventing death.

One stage percutaneous transhepatic biliary stenting for malignant jaundice: a safe, quick and economical option of treatment.

OBJECTIVE: Patients with proximal malignant jaundices are often diagnosed in an advanced stage and need biliary decompression treatments, such as percutaneous transhepatic biliary drainage (PTBD) and bare metal stenting (BMS), to improve the hepatic function. Whether it is better to perform those two procedures together or in a separate time, it is not well understood. The aim of this study was to investigate the effectiveness and cost-benefit of a combined "one-stage" PTBD/BMS procedure in patients with malignant jaundices. PATIENTS AND METHODS: Forty-five patients with malignant jaundice treated with "one-stage" PTBD/BMS were retrospectively enrolled to evaluate technical success, complications, survival, and length of hospitalization. RESULTS: A full technical success of the procedures was reported for all patients, with only one major complication among 45 treated patients. A better performance in terms of hospitalization rate was achieved by the one-stage procedure compared to the two-stage, also resulting in global saving of costs. A high survival rate was observed at the 3rd and 6th month (97.7% and 86.6%, respectively), with a median overall survival time of 271,58 days. CONCLUSIONS: Our study shows that performing PTBD/BMS as a "one-stage" procedure is useful, safe, and cost-effective with a high percentage of technical success and a similar occurrence of complications compared to the two-stage procedure.

Sputum proteomic signature of gastro-oesophageal reflux in patients with severe asthma.

Gastro-oesophageal reflux disease (GORD) has long been associated with poor asthma control without an established cause-effect relationship. 610 asthmatics (421 severe/88 mild-moderate) and 101 healthy controls were assessed clinically and a subset of 154 severe asthmatics underwent proteomic analysis of induced sputum using untargeted mass spectrometry, LC-IMS-MSE. Univariate and multiple logistic regression analyses (MLR) were conducted to identify proteins associated with GORD in this cohort. When compared to mild/moderate asthmatics and healthy individuals, respectively, GORD was three- and ten-fold more prevalent in severe asthmatics and was associated with increased asthma symptoms and oral corticosteroid use, poorer quality of life, depression/anxiety, obesity and symptoms of sino-nasal disease. Comparison of sputum proteomes in severe asthmatics with and without active GORD showed five differentially abundant proteins with described roles in anti-microbial defences, systemic inflammation and epithelial integrity. Three of these were associated with active GORD by multiple linear regression analysis: Ig lambda variable 1-47 (p = 0·017) and plasma protease C1 inhibitor (p = 0·043), both in lower concentrations, and lipocalin-1 (p = 0·034) in higher concentrations in active GORD. This study provides evidence which suggests that reflux can cause subtle perturbation of proteins detectable in the airways lining fluid and that severe asthmatics with GORD may represent a distinct phenotype of asthma.

Accuracy of the Orientation Estimate Obtained Using Four Sensor Fusion Filters Applied to Recordings of Magneto-Inertial Sensors Moving at Three Rotation Rates.

Magneto-Inertial technology is a well-established alternative to optical motion capture for human motion analysis applications since it allows prolonged monitoring in free-living conditions. Magneto and Inertial Measurement Units (MIMUs) integrate a triaxial accelerometer, a triaxial gyroscope and a triaxial magnetometer in a single and lightweight device. The orientation of the body to which a MIMU is attached can be obtained by combining its sensor readings within a sensor fusion framework. Despite several sensor fusion implementations have been proposed, no well-established conclusion about the accuracy level achievable with MIMUs has been reached yet. The aim of this preliminary study was to perform a direct comparison among four popular sensor fusion algorithms applied to the recordings of MIMUs rotating at three different rotation rates, with the orientation provided by a stereophotogrammetric system used as a reference. A procedure for suboptimal determination of the parameter filter values was also proposed. The findings highlighted that all filters exhibited reasonable accuracy (rms errors <; 6.4°). Moreover, in accordance with previous studies, every algorithm's accuracy worsened as the rotation rate increased. At the highest rotation rate, the algorithm from Sabatini (2011) showed the best performance with errors smaller than 4.1° rms.

Early-adolescent male C57BL/6J and DBA/2J mice display reduced sensitivity to acute nicotine administration.

BACKGROUND: The initial response to nicotine is an important predictor of subsequent use. Multiple factors may alter this response including genetics and age of first use. Here we investigated the influence of age, genetics, and their interaction on nicotine sensitivity. We then examined whether these factors influence the relationship between initial behavioral responses and voluntary nicotine consumption in adulthood. METHODS: We measured initial nicotine responses, including nicotine-induced locomotor depression and hypothermia following an acute intraperitoneal injection (0, 0.5, or 1 mg/kg), during early-adolescence, middle-adolescence, late-adolescence, or adulthood. Thirty-five days after the initial testing, mice were assessed for voluntary oral nicotine consumption. RESULTS: Early-adolescent mice were more resistant to nicotine-induced hypothermia and locomotor depression than later ages, further hypothermia was influenced by genetics. In the DBA/2J strain, early-adolescent mice were insensitive to nicotine-induced hypothermia, but this response developed at later ages. In contrast, C57BL/6J mice were sensitive at all ages, but sensitivity increased across developmental age. There was little evidence of a relationship between initial behavioral response and choice nicotine consumption. CONCLUSION: By understanding how age of exposure and genetics influence initial nicotine behavioral responses, we have a greater understanding of factors that make adolescents differentially sensitive to the effects of this drug.

Different Blood Flow Models in Coronary Artery Diseases: Effects on hemodynamic parameters.

Coronary arteries are medium-small caliber vessels, in which low shear rate values are encountered, where non-Newtonian blood effects cannot be neglected. This work aims to study a comparison between Newtonian and non-Newtonian blood behaviors in a cohort offorty-eight 3D patient-specific stenotic vessels (right (RCA), left (LAD) and circumflex (LCX) coronary artery) at different grades of stenosis. Numerical simulation was carried out by means of Computational Fluid Dynamics (CFD) Analysis to investigate the blood velocity and distribution of the shear stress indices at different times of the cardiac cycle. A statistical analysis was performed to have a prediction ofincrement or decrement ofthe various hemodynamic parameters. The results show that the non-Newtonian effects are mostly important in shear stress indices distributions.

Adolescent social stress increases anxiety-like behavior and ethanol consumption in adult male and female C57BL/6J mice.

Exposure to social stress is an important risk factor for comorbid affective disorders and problem alcohol use. To better understand mechanisms involved in social stress-induced affective disorder and alcohol use co-morbidity, we studied the effects of adolescent social stress on anxiety- and depression-like behaviors and binge-like ethanol consumption. Male and female C57BL/6J mice were exposed to chronic variable social stress (CVSS) or control conditions throughout adolescence (postnatal days, PND, 25-59) and then tested for anxiety-like behavior in the elevated plus maze and a novel open field environment, or depression-like behavior using the forced swim test on PND 64-66. Mice were then tested for binge-like ethanol consumption using the Drinking-in-the-Dark model. Male and female mice exposed to adolescent CVSS had increased adult anxiety-like behavior and increased locomotor adaptation to a novel environment. Further, CVSS mice consumed significantly more ethanol, but not saccharin, than controls. Despite group differences in both anxiety-like behavior and ethanol consumption, there was no relationship between these outcomes within individual mice. These data suggest that exposure to adolescent social stress is an important risk factor for later alcohol use and affective behaviors, but that social stress does not necessarily dictate co-morbidity of these outcomes.

Potato Consumption Is not Associated with Higher Risk of Mortality: A Longitudinal Study among Southern Italian Older Adults.

OBJECTIVE: The consumption of potatoes is increasing worldwide, but few studies have assessed the association between potato consumption and mortality, particularly in Mediterranean countries. We therefore investigated whether potato consumption is associated with higher risk of death in a large cohort of people living in South Italy. DESIGN: Longitudinal. SETTING: Community-dwelling. MEASUREMENTS: 2,442 participants coming from MICOL and NUTRIHEP studies aged more than 50 years at baseline were followed-up for 11 years. Dietary intake was assessed by means of a Food Frequency Questionnaire. Potato consumption was categorized in quintiles according to their daily consumption (< 3.95, 3.96-8.55, 8.56-15.67, 15.68-22.0, and > 22.0 g/day). Mortality was ascertained through validated cases of death. The association between potato consumption and mortality was assessed through Cox's regression models, adjusted for potential confounders, and reporting the data as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: The 2,442 eligible participants were prevalently males (54.6%) and aged a mean of 64.3±9.3 years. During the 11-year follow-up, 396 (=16.2%) participants died. After adjusting for 12 potential baseline confounders, and taking those with the lowest consumption of potatoes as the reference group, participants with the highest consumption of potatoes did not have an increased overall mortality risk (HR=0.75; 95%CI: 0.53-1.07). Modelling the potato consumption as continuous (i.e. as increase in 10 g/day) did not substantially change our findings (fully-adjusted HR=0.93; 95%CI: 0.84-1.02). CONCLUSION: Overall potato consumption was not associated with higher risk of death in older people living in a Mediterranean area. Future studies are warranted to elucidate the role of potato consumption on all-cause and cause-specific mortality.

Translating the combination of gene therapy and tissue engineering for treating recessive dystrophic epidermolysis bullosa.

The combination of gene therapy and tissue engineering is one of the most promising strategies for the treatment of recessive dystrophic epidermolysis bullosa (RDEB). RDEB is a rare genetic disease characterised by mutations in the COL7A1 gene, encoding type VII collagen (COLVII), which forms anchoring fibrils at the dermal-epidermal junction of the skin. This disease causes severe blistering and only palliative treatments are offered. In this study, the base of a strategy combining gene therapy and a tissue-engineered skin substitute (TES), which would be suitable for the permanent closure of skin wounds, was set-up. As a high transduction efficiency into fibroblasts and/or keratinocytes seems to be a prerequisite for a robust and sustained correction of RDEB, different envelope pseudotyped retroviral vectors and the transduction enhancer EF-C were tested. When green fluorescent protein (GFP) was used as a reporter gene to evaluate the retroviral-mediated gene transfer, the fibroblast infection efficiency was 30 % higher with the Ampho pseudotyped vector as compared with the other pseudotypes. At least a 3.1-fold and a 1.3-fold increased transduction were obtained in fibroblasts and keratinocytes, respectively, with EF-C as compared with polybrene. A continuous and intense deposit of haemagglutinin (HA)-COLVII was observed at the dermal-epidermal junction of self-assembled TESs made of cells transduced with a HA-tagged COL7A1 vector. Furthermore, HA-tagged basal epidermal cells expressing keratin 19 were observed in TESs, suggesting stem cell transduction. This approach could be a valuable therapeutic option to further develop, in order to improve the long-term life quality of RDEB patients.

Adolescent chronic variable social stress influences exploratory behavior and nicotine responses in male, but not female, BALB/cJ mice.

Anxiety disorders and nicotine use are significant contributors to global morbidity and mortality as independent and comorbid diseases. Early-life stress, potentially via stress-induced hypothalamic-pituitary-adrenal axis (HPA) dysregulation, can exacerbate both. However, little is known about the factors that predispose individuals to the development of both anxiety disorders and nicotine use. Here, we examined the relationship between anxiety-like behaviors and nicotine responses following adolescent stress. Adolescent male and female BALB/cJ mice were exposed to either chronic variable social stress (CVSS) or control conditions. CVSS consisted of repeated cycles of social isolation and social reorganization. In adulthood, anxiety-like behavior and social avoidance were measured using the elevated plus-maze (EPM) and social approach-avoidance test, respectively. Nicotine responses were assessed with acute effects on body temperature, corticosterone production, locomotor activity, and voluntary oral nicotine consumption. Adolescent stress had sex-dependent effects on nicotine responses and exploratory behavior, but did not affect anxiety-like behavior or social avoidance in males or females. Adult CVSS males exhibited less exploratory behavior, as indicated by reduced exploratory locomotion in the EPM and social approach-avoidance test, compared to controls. Adolescent stress did not affect nicotine-induced hypothermia in either sex, but CVSS males exhibited augmented nicotine-induced locomotion during late adolescence and voluntarily consumed less nicotine during adulthood. Stress effects on male nicotine-induced locomotion were associated with individual differences in exploratory locomotion in the EPM and social approach-avoidance test. Relative to controls, adult CVSS males and females also exhibited reduced corticosterone levels at baseline and adult male CVSS mice exhibited increased corticosterone levels following an acute nicotine injection. Results suggest that the altered nicotine responses observed in CVSS males may be associated with HPA dysregulation. Taken together, adolescent social stress influences later-life nicotine responses and exploratory behavior. However, there is little evidence of an association between nicotine responses and prototypical anxiety-like behavior or social avoidance in BALB/cJ mice.

Pro-inflammatory dietary pattern is associated with fractures in women: an eight-year longitudinal cohort study.

In this study, during 8 years of follow-up, we reported that higher dietary inflammatory index values were associated with a higher risk of incident fractures in women, but not in men, after adjusting for potential confounders. INTRODUCTION: Inflammation is a key risk factor for many adverse outcomes in older people. While diet is a potential source of inflammation, little is known about the impact of inflammatory diet on fractures. Thus, we investigated whether higher Dietary Inflammatory Index (DII)™ ® scores are associated with fractures in a cohort of North American people. METHODS: This longitudinal study with a follow-up of 8 years included 3648 participants (1577 males and 2071 females; mean age = 60.6 years) with/at risk of knee osteoarthritis participating with in the Osteoarthritis Initiative. DII scores were calculated using the validated Block Brief 2000 Food Frequency Questionnaire, categorized into sex-specific quintiles. Information on fractures was obtained through self-reported history of fractures at hip, spine, and forearm. The relationship between baseline DII score and incident fracture was assessed through a Cox's regression analysis, adjusted for potential baseline confounders, and reported as hazard ratios (HRs). RESULTS: During 8 years of follow-up, 560 individuals developed fractures (15.4%). Adjusting for 10 potential confounders, women in the highest DII score quintile (i.e., most pro-inflammatory diet) had a significantly higher risk for fractures (HR = 1.46; 95% CI = 1.02-2.11) compared to women in the lowest quintile. An increase in one standard deviation of DII scores significantly predicted fracture onset in women (adjusted HR = 1.14; 95% CI = 1.02-1.27). The association between DII score and fractures was not significant among men or in the sample as whole. CONCLUSION: Pro-inflammatory diet is associated with a higher incidence of fractures in women but not men.

A comparative study between responses of isolated bovine and equine digital arteries to vasoactive mediators.

Hemodynamic perturbations, partly resulting from abnormal vasoconstriction of digital vessels, have been implicated in the pathogenesis of bovine and equine laminitis. This study compared the responsiveness of isolated bovine (BDA) and equine (EDA) digital arteries to pharmacological agents that stimulate receptor systems involved in the regulation of normal vessel tone. The role of the endothelium and the short- and longer-term effects of an experimentally induced endothelial damage were also evaluated. Species-related differences were found in the vessel reactivity to all of the receptor agonists tested. In intact BDA, as compared to intact EDA, norepinephrine was a more effective vasoconstrictor, 5-hydroxytryptamine a more effective but less potent vasoconstrictor, isoproterenol a less effective vasodilator and carbamylcholine a less potent vasodilator. In BDA, but not in EDA, the contractile responses to norepinephrine and 5-hydroxytryptamine were enhanced immediately after endothelium removal. However, the contractile reactivity of denuded BDA returned to basal values following overnight incubation. The differences suggest species specificity for the pathophysiology of digital vasomotor tone and function in horses and cattle.

TNFα deficiency results in increased IL-1ß in an early onset of spontaneous murine colitis.

Inflammatory bowel disease (Crohn's disease (CD) and ulcerative colitis (UC)) is a multifactorial disease resulting from immune dysregulation in the gut. The underlying colitis is characterized by high levels of inflammatory cytokines, including TNFα. Biological intervention for IBD patients using anti-TNFα antibodies is often an effective therapeutic solution. However, TNFα neutralization fails to induce remission in a subgroup of IBD patients, primarily in UC patients. There is a dearth of suitable animal models representing TNFα non-responders. Here we have combined one of the best UC models currently available, namely Winnie and the TNFαKO mouse to generate a TNFα-deficient Winnie to study early onset colitis. The induced TNFα deficiency with underlying colitis does not influence general health (viability and body weight) or clinical parameters (colon weight, colon length and histological colitis) when compared with the Winnie genotype alone. The molecular characterization resulted in identification of Il1ß as the major elevated cytokine during early phases of colitis. Further, in vitro functional assay using bone marrow-derived dendritic cells confirmed IL-1ß as the major cytokine released in the absence of TNFα. This study has generated a successful model of colitis that remains TNFα non-responsive and has demonstrated that IL-1ß expression is a major pathway for the progression of colitis in this system. These data also suggest that IL-1ß can be a potential target for clinical intervention of UC patients who fail to respond to TNFα neutralization.