Hybrid coracoclavicular and acromioclavicular reconstruction in chronic acromioclavicular joint dislocations yields good functional and radiographic results

Purpose Optimal treatment of chronic unstable acromioclavicular (AC) joint dislocations (stage 3-5 according the Rockwood classification) is still debated. Anatomic coracoclavicular (CC) reconstruction is a reliable option in terms of two-dimensional radiographic reduction, clinical outcomes, and return to sports, but there remain concerns regarding anterior-posterior stability of the AC joint with CC ligament reconstruction alone. The aim of the present study was to describe the mid-term results of a new hybrid technique with CC and AC ligament reconstruction for chronic AC joint dislocations. Methods Twenty-two patients surgically treated for chronic AC joint dislocations (grade 3 to 5) were retrospectively reviewed. All patients were assessed before surgery and at final follow-up with the Constant-Murley score (CMS) and the American Shoulder and Elbow Surgeons (ASES) score. The CC vertical distance (CCD) and the CCD ratio (affected side compared to unaffected side) were measured on Zanca radiographs preoperatively, at 6 months postop and at final follow-up. The same surgical technique consisting in a primary fixation with a suspensory system, coracoclavicular ligaments reconstruction with a double loop of autologous gracilis and acromioclavicular ligaments reconstruction with autologous coracoacromial ligament was performed in all cases. Results Twenty-two shoulders in 22 patients (19 males and 3 females) were evaluated with a mean age of 34.4 +/- 9 years at the time of surgery. The mean interval between the injury and surgery was 53.4 +/- 36.7 days. The mean duration of postoperative follow-up was 49.9 +/- 11.8 months. According to the Rockwood classification, there were 5 (22.6%) type-III and 17 (77.2%) type-V dislocations. Mean preoperative ASES and CMS were 54.4 +/- 7.6 and 64.6 +/- 7.2, respectively. They improved to 91.8 +/- 2.3 (p = 0.0001) and 95.2 +/- 3.1 (p = 0.0001), respectively at final FU. The mean preoperative CCD was 22.4 +/- 3.2 mm while the mean CCD ratio was 2.1 +/- 0.1. At final FU, the mean CCD was 11.9 +/- 1.4 mm (p = 0.002) and the mean CCD ratio was 1.1 +/- 0.1 (p = 0.009). No recurrence of instability was observed. One patient developed a local infection and four patients referred some shoulder discomfort. Heterotopic ossifications were observed in three patients. Conclusions The optimal treatment of chronic high-grade AC joint dislocations requires superior-inferior and anterior-posterior stability to ensure good clinical outcomes and return to overhead activities or sports. The present hybrid technique of AC and CC ligaments reconstruction showed good clinical and radiographic results and is a reliable an alternative to other reported techniques

Assessing the Functional Relevance of Variants in the IKAROS Family Zinc Finger Protein 1 (IKZF1) in a Cohort of Patients With Primary Immunodeficiency

Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency. Patients with CVID are prone to recurrent bacterial infection due to the failure of adequate immunoglobulin production. Monogenetic defects have been identified in ~25% of CVID patients. Recently, mutations in IKZF1, encoding the zinc-finger transcription factor IKAROS which is broadly expressed in hematopoietic cells, have been associated with a CVID-like phenotype. Herein we describe 11 patients with heterozygous IKZF1 variants from eight different families with autosomal dominant CVID and two siblings with an IKZF1 variant presenting with inflammatory bowel disease (IBD). This study shows that mutations affecting the DNA binding domain of IKAROS can impair the interaction with the target DNA sequence thereby preventing heterochromatin and pericentromeric localization (HC-PC) of the protein. Our results also indicate an impairment of pericentromeric localization of IKAROS by overexpression of a truncated variant, caused by an immature stop codon in IKZF1. We also describe an additional variant in TNFSF10, encoding Tumor Necrosis Factor Related Apoptosis Inducing Ligand (TRAIL), additionally presented in individuals of Family A. Our results indicate that this variant may impair the TRAIL-induced apoptosis in target cell lines and prohibit the NFκB activation by TRAIL and may act as a modifier in Family A.Fil: Eskandarian, Zoya. Albert Ludwigs University of Freiburg; AlemaniaFil: Fliegauf, Manfred. Albert Ludwigs University of Freiburg; AlemaniaFil: Bulashevska, Alla. Albert Ludwigs University of Freiburg; AlemaniaFil: Proietti, Michele. Albert Ludwigs University of Freiburg; AlemaniaFil: Hague, Rosie. Royal Hospital For Children; Reino UnidoFil: Smulski, Cristian Roberto. Albert Ludwigs University of Freiburg; Alemania. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Schubert, Desirée. Albert Ludwigs University of Freiburg; AlemaniaFil: Warnatz, Klaus. Albert Ludwigs University of Freiburg; AlemaniaFil: Grimbacher, Bodo. Albert Ludwigs University of Freiburg; Alemania. University College London; Reino Unid

Regional diastolic function by tissue Doppler echocardiography in systemic sclerosis: correlation with clinical variables

The incidence of left ventricular (LV) diastolic dysfunction is increased in systemic sclerosis (SSc), while systolic dysfunction is present in a small percentage of patients. The aim of this study was to asses the LV "regional" diastolic abnormalities in SSc patients by the mean of Doppler tissue imaging (DTI). Echocardiographic echo-Doppler (DE) and DTI parameters were analyzed for 67 SSc patients: abnormal E/A ratio at DE was detected in 24, while abnormal e/a at DTI was observed in 41. A significant prevalence of DTI diastolic abnormalities in the segments reflecting longitudinal versus those reflecting radial LV motion was found. The segments of the basal regions of LV myocardium were significantly more involved than those of the middle portion. Linear correlation was observed between the extent of the diastolic abnormalities and the duration of disease. Longitudinal myocardial systolic velocities were significantly reduced in patients with abnormal e/a DTI

Spatially, Temporally, and Quantitatively Controlled Delivery of Broad Range of Molecules into Selected Cells through Plasmonic Nanotubes

A Universal plasmonic/microfluidic platform for spatial and temporal controlled intracellular delivery is described. The system can inject/transfect the desired amount of molecules with an efficacy close to 100%. Moreover, it is highly scalable from single cells to large ensembles without administering the molecules to an extracellular bath. The latter enables quantitative control over the amount of injected molecules

ATP released by intestinal bacteria limits the generation of protective IgA against enteropathogens

T cell dependent secretory IgA (SIgA) generated in the Peyer’s patches (PPs) of the small intestine shapes a broadly diverse microbiota that is crucial for host physiology. The mutualistic co-evolution of host and microbes led to the relative tolerance of host’s immune system towards commensal microorganisms. The ATP-gated ionotropic P2X7 receptor limits T follicular helper (Tfh) cells expansion and germinal center (GC) reaction in the PPs. Here we show that transient depletion of intestinal ATP can dramatically improve high-affinity IgA response against both live and inactivated oral vaccines. Ectopic expression of Shigella flexneri periplasmic ATP-diphosphohydrolase (apyrase) abolishes ATP release by bacteria and improves the specific IgA response against live oral vaccines. Antibody responses primed in the absence of intestinal extracellular ATP (eATP) also provide superior protection from enteropathogenic infection. Thus, modulation of eATP in the small intestine can affect highaffinity IgA response against gut colonizing bacteria

Ectonucleotidase activity and immunosuppression in astrocyte-CD4 T cell bidirectional signaling

Astrocytes play a crucial role in neuroinflammation as part of the glia limitans, which regulates infiltration of the brain parenchyma by leukocytes. The signaling pathways and molecular events, which result from the interaction of activated T cells with astrocytes are poorly defined. Here we show that astrocytes promote the expression and enzymatic activity of CD39 and CD73 ectonucleotidases in recently activated CD4 cells by a contact dependent mechanism that is independent of T cell receptor interaction with class II major histocompatibility complex (MHC). Transforming growth factor-β (TGF-β) is robustly upregulated and sufficient to promote ectonucleotidases expression. T cell adhesion to astrocyte results in differentiation to an immunosuppressive phenotype defined by expression of the transcription factor Rorγt, which characterizes the CD4 T helper 17 subset. CD39 activity in T cells in turn inhibits spontaneous calcium oscillations in astrocytes that correlated with enhanced and reduced transcription of CCL2 chemokine and Sonic hedgehog (Shh), respectively. We hypothesize this TCR-independent interaction promote an immunosuppressive program in T cells to control possible brain injury by deregulated T cell activation during neuroinflammation. On the other hand, the increased secretion of CCL2 with concomitant reduction of Shh might promote leukocytes extravasation into the brain parenchyma

Biodiversity and bioprospecting of fungal endophytes from the Antarctic plant Colobanthus quitensis

Microorganisms from extreme environments are considered as a new and valuable reservoir of bioactive molecules of biotechnological interest and are also utilized as tools for enhancing tolerance to (a)biotic stresses in crops. In this study, the fungal endophytic community associated with the leaves of the Antarctic angiosperm Colobanthus quitensis was investigated as a new source of bioactive molecules. We isolated 132 fungal strains and taxonomically annotated 26 representative isolates, which mainly belonged to the Basidiomycota division. Selected isolates of Trametes sp., Lenzites sp., Sistotrema sp., and Peniophora sp. displayed broad extracellular enzymatic profiles; fungal extracts from some of them showed dose-dependent antitumor activity and inhibited the formation of amyloid fibrils of α-synuclein and its pathological mutant E46K. Selected fungal isolates were also able to promote secondary root development and fresh weight increase in Arabidopsis and tomato and antagonize the growth of pathogenic fungi harmful to crops. This study emphasizes the ecological and biotechnological relevance of fungi from the Antarctic ecosystem and provides clues to the bioprospecting of Antarctic Basidiomycetes fungi for industrial, agricultural, and medical applications

Single-Metabolite Bio-Nano-Sensors and System for Remote Monitoring in Animal Models

A novel system for remote monitoring of metabolism in animal model is proposed in this paper. The system is obtained by integrating Bio-Nano-Sensors to detect single- metabolites, an electrochemical front-end made with off- the-shelf components, an RF communication sub-system, and an antenna of new design. The system has been calibrated and tested for continuous monitoring of four different metabolites: glucose, lactate, glutamate, and adenosine triphosphate (ATP). Tests with animal models (mice) have been conducted to investigate tissue inflammation induced by the implanted Bio-Nano- Sensors. The tests confirmed that our system is suitable and reliable for remote monitoring of single-metabolites in experiments with animal models

Remote System for Monitoring Animal Models With Single-Metabolite Bio-Nano-Sensors

A novel system for remote monitoring of metabolism in an animal model is proposed in this paper. The system is obtained by integrating bio-nano-sensors to detect single- metabolites, an electrochemical front-end made with off-the-shelf components, a radio frequency communication sub-system, and an antenna of new design. The system has been calibrated and tested for continuous monitoring of four different metabolites: glucose, lactate, glutamate, and adenosine triphosphate. Tests using animal models (mice) have been conducted to investigate tissue inflammation induced by the implanted bio-nano-sensors. These tests confirm that our system is suitable and reliable for remote monitoring of single-metabolites in experiments with animal models

The APpendicitis PEdiatric (APPE) score: a new diagnostic tool in suspected pediatric acute appendicitis

Our aim was to develop an APpendictis-PEdiatric score (APPE score) in quantifying risk of acute appendicitis based on combination of clinical and laboratory markers. 1025 patients were classified in: acute appendicitis (AA) and non-appendicitis. Demographic/clinical features, and laboratory were collected. They were compared for quantitative-variables and categorical-variables. Significant predictors (P=<0,05) were included in logistic regression model. Based on regression-coefficients, a diagnostic score was tested by calculating the area under the ROC curve. Two cut-offs were established to define classes of risk of AA. 9 variables were identified as potentially predictors for AA. Those underwent logistic regression and a score was assigned, for maximum 21-points. The score showed an area under the curve: 0.831 and a linear proportion with the state of appendicular inflammation (R20.85). Patients with a score ≤8 were at low risk of AA (sensitivity 94%); those with a score ≥15 were at high risk for AA (specificity 93%). Those between 8 and 15 were defined at intermediate risk class. APPE-score guides clinicians in classifying patients with suspected-AA according to clinical and laboratory findings in order to improve their management