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Although numerous articles have been published not only on the classification of thoracic outlet syndrome (TOS) but also on diagnostic standards, timing, and type of surgical intervention, there still remains some controversy because of the lack of level 1 evidence. So far, attempts to generate uniform reporting standards have not yielded conclusive results. OBJECTIVE: To systematically review the body of evidence and reach a consensus among neurosurgeons experienced in TOS regarding anatomy, diagnosis, and classification. METHODS: A systematic literature search on PubMed/MEDLINE was performed on February 13, 2021, yielding 2853 results. Abstracts were screened and classified. Recommendations were developed in a meeting held online on February 10, 2021, and refined according to the Delphi consensus method. RESULTS: Six randomized controlled trials (on surgical, conservative, and injection therapies), 4 “guideline” articles (on imaging and reporting standards), 5 observational studies (on diagnostics, hierarchic designs of physiotherapy vs surgery, and quality of life outcomes), and 6 meta-analyses were identified. The European Association of Neurosurgical Societies’ section of peripheral nerve surgery established 18 statements regarding anatomy, diagnosis, and classification of TOS with agreement levels of 98.4 % (±3.0). CONCLUSION: Because of the lack of level 1 evidence, consensus statements on anatomy, diagnosis, and classification of TOS from experts of the section of peripheral nerve surgery of the European Association of Neurosurgical Societies were developed with the Delphi method. Further work on reporting standards, prospective data collections, therapy, and long-term outcome is necessary.

It is generally accepted that Glioblastoma (GBM) arise from cancer stem cells (CSC), however, there is little evidence on their anatomical distribution. We investigated the expression and distribution of SOX-2-positive and CD133-positive CSCs both in the enhancing nodule (EN) of GBM and in the FLAIR hyperintensity zones on a surgical, histopathological series of 33 GBMs.The inclusion criterion was the intraoperative sampling of different tumor regions individualized thanks to Neuronavigation and positivity to intraoperative fluorescence with the use of 5-aminolevulinic acid (5-ALA). 33 patients (20 males and 13 females with a mean age at diagnosis of 56 years) met the inclusion criterion. A total of 109 histological samples were evaluated, 52 for ENs and 57 for FLAIR hyperintensity zone. Considering the quantitative distribution of levels of intensity of staining (IS), ES (extent score) and immunoreactivity score (IRS), no difference was found between ENs and FLAIR regions for both the SOX-2 biomarker (respectively, IS p=0.851, ES p=0.561, IRS p=1.000) and the CD133 biomarker (IS p=0.653, ES p=0.409, IRS p=0.881). This evidence suggests to recalibrate the target of surgery for FLAIRECTOMY and 5-ALA could improve the possibility to achieve this goal.

Greinacher et al.1 and Schultz et al.2 were the first to independently report the main clinical and laboratory features of 11 and five respective patients from Germany, Austria and Norway who developed life-threatening thrombohemorrhagic complications 5 to 16 days after the administration of the first dose of the chimpanzee adenoviral vector vaccine ChAdOx1nCoV-19 against SARS-CoV-2 and COVID-19. Subsequently Scully et al.3 reported similar findings in 23 patients treated with the same vaccine in the United Kingdom. More recently, See et al.4 reported a case series of 12 patients from the USA with cerebral venous sinus thrombosis following the vaccination with Ad26.CoV2.S employing a human adenoviral vector. The main post-vaccination features common to the case series were the occurrence of venous thromboembolism mainly in unusual sites (cerebral and abdominal veins) and the concomitant presence of bleeding symptoms associated with severe thrombocytopenia, often accompanied by laboratory signs of consumption coagulopathy with low plasma fibrinogen and hugely increased levels of D-dimer. The majority of reported patients reacted positively for serum immunoglobulin G (IgG) antibodies to the platelet factor 4 PF4/heparin complex. 1-4 Another common feature was the high mortality rate. The mechanism of this very rare thrombohemorrhagic syndrome was postulated to be a vaccine-triggered autoimmune reaction, with the development of antibodies against a still ill-defined PF4/polyanion complex that causes platelet activation as in heparin-induced thrombocytopenia (HIT),1-4 notwithstanding the fact that no cases were exposed to heparin before the onset of thrombosis and thrombocytopenia. We report herewith the detailed post-mortem macroscopic and microscopic findings in two similar cases that occurred in the Italian region of Sicily.

Breast cancer is a growing global public health concern. Thanks to the recent treatments progress, the survival rate of BC patients has significantly improved (88% of 5-year survival rate) and the number of cancer survivors has also increased. Notwithstanding these brilliant results, many BC patients have long-term side effects as pain, oedema, limited mobility, cancer related fatigue, etc. as a consequence of surgical, radiotherapy and medical treatments. For example, posture appears to be frequently altered after mastectomy, due to the impairment of the mobility of the arm caused by surgical scars. All these aspects negatively affect the health-related Quality of Life (QoL) of BC patients. Recent several randomized clinical trials have shown benefits of regular and appropriate physical activity (PA) during and after BC treatment, particularly in terms of benefits for health, reducing fatigue, improving strength levels, QoL and physical function. In this context, two types of sports have demonstrated their affinity and efficacy as treatment support during and after treatments for BC patients: fencing and rowing. Here we report considerations shared with two sport champions: the fencing Olympic gold medal Daniele Garozzo and the rowing World Champion Giovanni Ficarra, with the aim to find the adapted PA for BC patients.

We report a case of brucellosis-induced severe neutropenia in a 2-year-old girl who presented with a 2-week history of fever. On clinical examination, the patient was febrile with mild aphthous stomatitis. However, her general condition was stable, and systemic examination did not show involvement of any other organ. Laboratory test results revealed severe neutropenia, mild anemia, and an elevated serum C-reactive protein level. Flow cytometry of peripheral blood leukocytes revealed no malignancy, and blood film morphology was unremarkable except for mild microcytosis and hypochromia. Antineutrophil antibody and Coombs test results were negative. We administered intravenous cefuroxime; however, therapy was switched to meropenem plus clarithromycin because fever persisted for 5 days, despite treatment. On the 10th day after admission, Brucella serology tests showed positive results, and trimethoprim-sulfamethoxazole plus rifampicin therapy was prescribed for 8 weeks. The fever defervesced, and the child was discharged in a good state of health. Neutropenia persisted for several months but gradually resolved. Neutropenia, defined as an absolute neutrophil count (ANC)1.5 cells × 10 9 /L beyond the first year of life, is a benign transient condition associated with an intercurrent infection (usually viral illnesses or infections) in immunocompetent children. However, severe neutropenia (ANC0.5 × 10 9 /L) associated with fever necessitates hospitalization and administration of broad-spectrum antibiotics to avoid the high risk of sepsis, particularly in children. Brucellosis is rarely associated with hematologic abnormalities such as neutropenia. Early diagnosis of hematologic complications of brucellosis is essential for prompt initiation of specific and aggressive treatment.

N-glycan analyses may serve uncovering disease-associated biomarkers, as well as for profiling distinctive changes supporting diagnosis of genetic disorders of glycan biosynthesis named congenital disorders of glycosylation (CDG). Strategies based on liquid chromatography (LC) preferentially coupled to electrospray ionization (ESI) - mass spectrometry (MS) have emerged as powerful analytical methods for N-glycan identification and characterization. To enhance detection sensitivity, glycans are commonly labelled with a functional tag prior to LC-MS analysis. Since most derivatization techniques are notoriously time-consuming, some commercial analytical kits have been developed to speed up N-deglycosylation and N-glycan labelling of glycoproteins of pharmaceutical and biological interest such as monoclonal antibodies (mAbs). We exploited the analytical capabilities of RapiFluor-MS (RFMS) to perform, by a slightly modified protocol, a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG). This strategy, accomplished by Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans, allowed us to uncover structural details of patients serum released N-glycans, thus extending the current knowledge on glycan profiles in these individual glycosylation diseases. The applied methodology enabled to differentiate in some cases either structural isomers and isomers differing in the linkage type. All the here reported applications demonstrated that RFMS method, coupled to HILIC-UPLC-ESI-MS, represents a sensitive high throughput approach for serum N-glycome analysis and a valuable option for glycan detection and separation particularly for isomeric species.

Ping-pong fractures have become less frequent, and no definite predictors to determine which fractures will elevate spontaneously and which should undergo surgical treatment have been clearly defined. Herein, the authors present a revision of the literature, in which 54 papers were included, with a total of 228 children studied. Patients who underwent surgery accounted for 30%; elevation through obstetrical vacuum or other aspiration systems was applied in 30%; and spontaneous resolution occurred in 40%; in 4 patients, percutaneous microscrew elevation was applied. Overall, in 96.4% of patients, the outcome was favorable because we found no significant increase in the incidence of post-traumatic seizures or neurologic sequelae with no significant differences between treated patients and spontaneous elevation. Statistical analysis showed no significant differences among the different treatment methods (P = 0.53). Our results suggest that simple compound ping-pong fractures without brain compression, hematomas, or dural tears could benefit from conservative management. In cases of nonspontaneous resolution after 6 months, operative strategies should be performed, considering that there is no evidence of differences between vacuum elevation and surgical elevation.

Vacuolar-type H+-ATPase (V-ATPase) is a multimeric complex present in a variety of cellular membranes that acts as an ATP-dependent proton pump and plays a key role in pH homeostasis and intracellular signalling pathways. In humans, 22 autosomal genes encode for a redundant set of subunits allowing the composition of diverse V-ATPase complexes with specific properties and expression. Sixteen subunits have been linked to human disease. Here we describe 26 patients harbouring 20 distinct pathogenic de novo missense ATP6V1A variants, mainly clustering within the ATP synthase α/β family-nucleotide-binding domain. At a mean age of 7 years (extremes: 6 weeks, youngest deceased patient to 22 years, oldest patient) clinical pictures included early lethal encephalopathies with rapidly progressive massive brain atrophy, severe developmental epileptic encephalopathies and static intellectual disability with epilepsy. The first clinical manifestation was early hypotonia, in 70%; 81% developed epilepsy, manifested as developmental epileptic encephalopathies in 58% of the cohort and with infantile spasms in 62%; 63% of developmental epileptic encephalopathies failed to achieve any developmental, communicative or motor skills. Less severe outcomes were observed in 23% of patients who, at a mean age of 10 years and 6 months, exhibited moderate intellectual disability, with independent walking and variable epilepsy. None of the patients developed communicative language. Microcephaly (38%) and amelogenesis imperfecta/enamel dysplasia (42%) were additional clinical features. Brain MRI demonstrated hypomyelination and generalized atrophy in 68%. Atrophy was progressive in all eight individuals undergoing repeated MRIs. Fibroblasts of two patients with developmental epileptic encephalopathies showed decreased LAMP1 expression, Lysotracker staining and increased organelle pH, consistent with lysosomal impairment and loss of V-ATPase function. Fibroblasts of two patients with milder disease, exhibited a different phenotype with increased Lysotracker staining, decreased organelle pH and no significant modification in LAMP1 expression. Quantification of substrates for lysosomal enzymes in cellular extracts from four patients revealed discrete accumulation. Transmission electron microscopy of fibroblasts of four patients with variable severity and of induced pluripotent stem cell-derived neurons from two patients with developmental epileptic encephalopathies showed electron-dense inclusions, lipid droplets, osmiophilic material and lamellated membrane structures resembling phospholipids. Quantitative assessment in induced pluripotent stem cell-derived neurons identified significantly smaller lysosomes. ATP6V1A-related encephalopathy represents a new paradigm among lysosomal disorders. It results from a dysfunctional endo-lysosomal membrane protein causing altered pH homeostasis. Its pathophysiology implies intracellular accumulation of substrates whose composition remains unclear, and a combination of developmental brain abnormalities and neurodegenerative changes established during prenatal and early postanal development, whose severity is variably determined by specific pathogenic variants.

BACKGROUND: Deficiency of Conserved Oligomeric Golgi (COG) subunits (COG1-8) is characterized by both N- and O-protein glycosylation defects associated with destabilization and mislocalization of Golgi glycosylation machinery components (COG-CDG). Patients with COG defects present with neurological and multisystem involvement and possible malformation occurrence. Eighteen patients with COG6-CDG (COG6 mutations) were reported to date. We describe a patient with COG6-CDG with novel variants and a novel clinical feature namely a congenital recto-vaginal fistula. METHODS: In-depth serum N- and O-glycosylation structural analyses were conducted by MALDI-TOF mass spectrometry. COG6 variants were identified by a gene panel and confirmed by Sanger sequencing. RESULTS: This female newborn presented with facial dysmorphism, distal arthrogryposis and recurrent stool discharges per vaginam. A double-contrast barium-enema X-ray study revealed a dehiscence (approximately 5 mm) at the anterior wall of the rectal ampoule communicating with the vagina consistent with a recto-vaginal fistula. She had developmental delay, corpus callosum dysgenesis, liver and gastrointestinal involvement, hyperthermia episodes and early demise. Serum N- and O-glycosylation analyses pointed to a profound Golgi disarrangement. We identified two novel variants in COG6: a deletion of 1 bp mutation c.823delA creating a shift in the reading frame and a premature stop codon and a 3 bp deletion (c.1141_1143delCTC) producing an in-frame deletion of 1 amino acid. CONCLUSION: The congenital recto-vaginal fistula is a rare type of anorectal malformation that, to our knowledge, has not been reported in patients with a COG6 defect nor in patients with other COG defects. This study broadens COG6-CDG genetic landscape and spectrum of malformations. ispartof: BIRTH DEFECTS RESEARCH vol:114 issue:5-6 pages:165-174 ispartof: location:United States status: published

Background and objectives Renin-angiotensin system (RAS) inhibitors reduce cardiovascular morbidity and mortality in patients with CKD. We evaluated the cardioprotective effects of the angiotensin-converting enzyme inhibitor ramipril in patients on maintenance hemodialysis. Design, setting, participants, & measurements In this phase 3, prospective, randomized, open-label, blinded end point, parallel, multicenter trial, we recruited patients on maintenance hemodialysis with hypertension and/or left ventricular hypertrophy from 28 Italian centers. Between July 2009 and February 2014, 140 participants were randomized to ramipril (1.25–10 mg/d) and 129 participants were allocated to non-RAS inhibition therapy, both titrated up to the maximally tolerated dose to achieve predefined target BP values. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the single components of the primary end point, new-onset or recurrence of atrial fibrillation, hospitalizations for symptomatic fluid overload, thrombosis or stenosis of the arteriovenous fistula, and changes in cardiac mass index. All outcomes were evaluated up to 42 months after randomization. Results At comparable BP control, 23 participants on ramipril (16%) and 24 on non-RAS inhibitor therapy (19%) reached the primary composite end point (hazard ratio, 0.93; 95% confidence interval, 0.52 to 1.64; P=0.80). Ramipril reduced cardiac mass index at 1 year of follow-up (between-group difference in change from baseline: −16.3 g/m2; 95% confidence interval, −29.4 to −3.1), but did not significantly affect the other secondary outcomes. Hypotensive episodes were more frequent in participants allocated to ramipril than controls (41% versus 12%). Twenty participants on ramipril and nine controls developed cancer, including six gastrointestinal malignancies on ramipril (four were fatal), compared with none in controls. Conclusions Ramipril did not reduce the risk of major cardiovascular events in patients on maintenance hemodialysis. Clinical Trial registry name and registration number: ARCADIA, NCT00985322 and European Union Drug Regulating Authorities Clinical Trials Database number 2008–003529–17.

Although reverse transcriptase quantitative PCR remains the gold standard to perform viral detection, reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) is already used to perform diagnosis of various infections. This work reports the results of a multicentric study performed in Sicily to evaluate the diagnostic power of an RT-LAMP kit for the diagnosis of SARS-CoV-2 infection on a total of 551 samples collected in January and February 2021, revealing sensitivity, specificity, accuracy, positive and negative predictive values ≥95%. Our results suggest the potential employment of this kit as a screening test to be used where fast and reliable results are demanded without the need for expensive instruments and highly-skilled personnel.

Alcaligenes faecalis is the predominant Gram‐negative bacterium inhabiting gut‐associated lymphoid tissues, Peyer's patches. We previously reported that an A. faecalis lipopolysaccharide (LPS) acted as a weak agonist for Toll‐like receptor 4 (TLR4)/myeloid differentiation factor‐2 (MD‐2) receptor as well as a potent inducer of IgA without excessive inflammation, thus suggesting that A. faecalis LPS might be used as a safe adjuvant. In this study, we characterized the structure of both the lipooligosaccharide (LOS) and LPS from A. faecalis. We synthesized three lipid A molecules with different degrees of acylation by an efficient route involving the simultaneous introduction of 1‐ and 4′‐phosphates. Hexaacylated A. faecalis lipid A showed moderate agonistic activity towards TLR4‐mediated signaling and the ability to elicit a discrete interleukin‐6 release in human cell lines and mice. It was thus found to be the active principle of the LOS/LPS and a promising vaccine adjuvant candidate., A host–microbe chemical ecology study revealed an effective and safe immunomodulator from Alcaligenes faecalis resident in gut‐associated lymphoid tissues, Peyer's patches (see picture). The complete structures of both the lipooligosaccharide and the lipopolysaccharide from A. faecalis were characterized. Furthermore, A. faecalis lipid A molecules were synthesized with varying degrees of acylation and found to be a promising vaccine adjuvant candidate.

Although most cysts of the male pelvis are benign and do not need treatment, some cysts may cause complications or have potential for malignancy, and using a workflow can help determine the most ap...

The proposal of reclassifying the mesentery as an organ prompts clinicians and radiologists to reappraise their approach to it and to mesenteric diseases (mesenteropathies). Recent updates in mesenteric anatomy and the better comprehension of its structure constitute a basis to push forward the process of disease management and allow the development of less radical (including endoscopic, radiological, and pharmacotherapeutic) treatments. Radiological evaluation currently plays a pivotal role in the noninvasive characterization of abdominal diseases. Mesenteric-based radiological assessments form an essential component in planning radiological interventions and postoperative surveillance programs. The purpose of this article, therefore, is to provide an update on the new anatomical concepts related to the mesentery, also performing an imaging-based review of mesenteric diseases by categorizing them as primary and secondary.

Congenital disorders of glycosylation (CDG) are genetic diseases characterized by deficient synthesis (CDG type I) and/or abnormal processing (CDG type II) of glycan moieties linked to protein and lipids. The impact of the molecular defects on protein glycosylation and in turn on the clinical phenotypes of patients with CDG is not yet understood. ALG12-CDG is due to deficiency of ALG12 α1,6-mannosyltransferase that adds the eighth mannose residue on the dolichol-PP-oligosaccharide precursor in the endoplasmic reticulum. ALG12-CDG is a severe multisystem disease associated with low to deficient serum immunoglobulins and recurrent infections. We thoroughly investigated the glycophenotype in a patient with novel ALG12 variants and immunodeficiency. We analyzed serum native transferrin, as first line test for CDG and we profiled serum IgG and total serum N-glycans by a combination of consolidated (N-glycan analysis by MALDI MS) and innovative mass spectrometry-based protocols, such as GlycoWorks RapiFluor N-glycan analysis coupled with LC-ESI MS. Intact serum transferrin showed, as expected for a CDG type I defect, underoccupancy of N-glycosylation sites. Surprisingly, total serum proteins and IgG N-glycans showed some specific changes, consisting in accumulating amounts of definite high-mannose and hybrid structures. As a whole, ALG12-CDG behaves as a dual CDG (CDG-I and II defects) and it is associated with distinct, abnormal glycosylation of total serum and IgG N-glycans. Glycan profiling of target glycoproteins may endorse the molecular defect unraveling the complex clinical phenotype of CDG patients.

Glycosylation is a complex post-translational modification that conveys functional diversity to glycoconjugates. Cell surface glycosylation mediates several biological activities such as induction of the intracellular signaling pathway and pathogen recognition. Red blood cell (RBC) membrane N-glycans determine blood type and influence cell lifespan. Although several proteomic studies have been carried out, the glycosylation of RBC membrane proteins has not been systematically investigated. This work aims at exploring the human RBC N-glycome by high-sensitivity MALDI-MS techniques to outline a fingerprint of RBC N-glycans. To this purpose, the MALDI-TOF spectra of healthy subjects harboring different blood groups were acquired. Results showed the predominant occurrence of neutral and sialylated complex N-glycans with bisected N-acetylglucosamine and core- and/or antennary fucosylation. In the higher mass region, these species presented with multiple N-acetyllactosamine repeating units. Amongst the detected glycoforms, the presence of glycans bearing ABO(H) antigens allowed us to define a distinctive spectrum for each blood group. For the first time, advanced glycomic techniques have been applied to a comprehensive exploration of human RBC N-glycosylation, providing a new tool for the early detection of distinct glycome changes associated with disease conditions as well as for understanding the molecular recognition of pathogens.

Membranous nephropathy represents the most frequent cause of nephrotic syndrome in the adult, leading to end-stage renal disease in one third of all the patients. In the last years, the discovery of circulating autoantibodies against phospholipase A2 receptor 1 (PLA2R) and thrombospondin type-1 containing 7A domain (THSD7A), shed light on the pathogenesis of idiopathic forms, being responsible for 70% and 3% of all the cases, respectively. These identifications allowed the development of serological and histologic tests to detect autoantibodies and relative targets for diagnostic and prognostic purposes. Rising evidences suggest that serum titer correlates with disease activity and response to therapy. For these reasons, for patients with nephrotic syndrome, a serum-based approach has been proposed, reserving renal biopsy only in cases with doubtful/negative serology. However, the recent introduction of useful criteria for the interpretation of PLA2R/THSD7A immunohistochemistry could lead to high values of sensitivity and specificity for the in situ detection of target antigens. The present multicentric study on a series of membranous nephropathy cases with available serum/histologic correlation will show the importance of the crosstalk among the different techniques, recovering the possible role of electron microscopy in challenging situations.

The Middle East is known for its complex history and rich environment and culture. The region is home to a wide variety of traditions, cultures and religions, which have made the area vulnerable to political conflicts. Despite these difficulties, science and medicine have always thrived in the region, with many medical practices and principles established by physicians and scholars living in the Middle East. The first academic neurosurgical activity in the region started in the 1950s. The first women neurosurgeons in the Middle East started training in the 1970s, and were from Iran, Palestine, followed by Saudi Arabia in the 1970s. These pioneers have encountered serious challenges, yet have become role models for the next generation. These women have paved the way and facilitated neurosurgical training and practice for more women surgeons. The gradual increase in the number of women neurosurgical residents in the region leads to the expectation that women will play a more prominent role in the future as leaders in neurosurgery in the Middle East. This collaborative study, which identifies the known women neurosurgeons in the Middle East for the first time, may serve to provide background and context for further contributions of women neurosurgeons for our profession and our patients.

We aimed to identify clinical, molecular and radiological correlates of activities of daily living (ADL) in patients with cerebellar atrophy caused by PMM2 mutations (PMM2-CDG), the most frequent congenital disorder of glycosylation. Twenty-six PMM2-CDG patients (12 males; mean age 13 ± 11.1 years) underwent a standardized assessment to measure ADL, ataxia (brief ataxia rating scale, BARS) and phenotype severity (Nijmegen CDG rating scale, NCRS). MRI biometry of the cerebellum and the brainstem were performed in 23 patients (11 males; aged 5 months–18 years) and 19 control subjects with equal gender and age distributions. The average total ADL score was 15.3 ± 8.5 (range 3–32 out of 36 indicating severe functional disability), representing variable functional outcome in PMM2-CDG patients. Total ADL scores were significantly correlated with NCRS (r2 = 0.55, p < 0.001) and BARS scores (r2 = 0.764; p < 0.001). Severe intellectual disability, peripheral neuropathy, and severe PMM2 variants were all significantly associated with worse functional outcome. Higher ADL scores were significantly associated with decreased diameters of cerebellar vermis (r2 = 0.347; p = 0.004), hemispheres (r2 = 0.436; p = 0.005), and brainstem, particularly the mid-pons (r2 = 0.64; p < 0.001) representing the major radiological predictor of functional disability score in multivariate regression analysis. We show that cerebellar syndrome severity, cognitive level, peripheral neuropathy, and genotype correlate with ADL used to quantify disease-related deficits in PMM2-CDG. Brainstem involvement should be regarded among functional outcome predictors in patients with cerebellar atrophy caused by PMM2-CDG.

Purpose Tear fluid N-Glycome from patients affected with vernal (VKC) and atopic keratoconjunctivitis (AKC) was investigated to identify specific changes in tears and to recognize possible glyco-biomarkers. Methods The analysis of the N-glycans was performed using matrix-assisted laser desorption ionization mass spectrometry on single tear samples. Tears from control normal subjects (CTRL), VKC and AKC patients were processed and treated with peptide N-glycosidase F (PNGase F) to deglycosylate N-glycoproteins. Released N-glycans were purified, permethylated, and analyzed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and tandem mass spectrometry (MALDI-TOF MS and MALDI-TOF MS/MS). Results More than 150 complex N-glycans, including highly fucosylated biantennary, triantennary, tetra-antennary, and bisecting species, were observed in our spectra. Three distinct patterns for CTRL, VKC, and AKC patients were identified in terms of relative intensities for some N-glycans structures. Major variations involved bisecting and hyperfucosylated glycoforms. The most intense ions were associated with species at m/z 1907.0 (asialo, agalacto, bisected, biantennary structure-NGA2B) in CTRL MS profiles, at m/z 2605.3 and 2966.5 in VKC, and at m/z 2792.4 in AKC corresponding to a well-known biantennary, disialylated N-glycan. Several peaks were associated with structures bearing one or two Lewis X epitopes. Structures were confirmed by MS/MS analysis. Quantitative differences among the three groups were statistically significant. Conclusions Tear MS profiles are rich in specific glycoforms, particularly those with a high fucosylation degree, indicating both core and peripheral decoration. Tear N-glycome analysis provided important information for a better comprehension of VKC and AKC alterations at the molecular level.

OBJECTIVENo consensus exists on the best treatment for recurrent high-grade glioma (HGG), particularly in terms of surgical indications, and scant data are available on the integrated use of multiple technologies to overcome intraoperative limits and pitfalls related to artifacts secondary to previous surgery and radiotherapy. Here, the authors report on their experience with the integration of multiple intraoperative tools in recurrent HGG surgery, analyzing their pros and cons as well as their effectiveness in increasing the extent of tumor resection. In addition, they present a review of the relevant literature on this topic.METHODSThe authors reviewed all cases in which recurrent HGG had been histologically diagnosed after a first surgery and the patient had undergone a second surgery involving neuronavigation with MRI, intraoperative CT (iCT), 11C-methionine–positron emission tomography (11C-MET-PET), 5-aminolevulinic acid (5-ALA) fluorescence, intraoperative neurophysiological monitoring (IONM), and intraoperative navigated ultrasound (iUS). All cases were classified according to tumor functional grade (1, noneloquent area; 2, near an eloquent area; 3, eloquent area).RESULTSTwenty patients with recurrent HGG were operated on using a multimodal protocol. The recurrent tumor functional grade was 1 in 4 patients, 2 in 8 patients, and 3 in the remaining 8 patients. In all patients but 2, 100% EOTR was obtained. Intraoperative 5-ALA fluorescence and navigated iUS showed low specificity and sensitivity. iCT detected tumor remnants in 3 cases. Postoperatively, 6 patients (30%) had worsening neurological conditions: 4 recovered within 90 days, 1 partially recovered, and 1 experienced a permanent deficit. The median Karnofsky Performance Status remained substantially unchanged over the follow-up period. The mean progression-free survival after the second surgery was 7.7 months (range 2–11 months). The mean overall survival was 25.4 months (range 10–52 months), excluding 2 long survivors. Two patients died within 60 days after surgery, and 3 patients were still under follow-up at the end of this study.CONCLUSIONSThis is the first study reporting the integration of neuronavigation, 5-ALA fluorescence, iUS, iCT, 11C-MET-PET, and IOM during microsurgical resection of recurrent glioma. The authors believe that the proposed multimodal protocol is useful to increase the safety, effectiveness, and EOTR in patients with recurrent HGG and brain alterations secondary to radio- and chemotherapy.

B-cell non-Hodgkin lymphomas (B-NHLs) are often characterized by the development of resistance to chemotherapeutic drugs and/or relapse. During drug-induced apoptosis, Yin Yang 1 (YY1) transcription factor might modulate the expression of apoptotic regulators genes. The present study was aimed to: (1) examine the potential oncogenic role of YY1 in reversing drug resistance in B-NHLs, and (2) identify YY1 transcriptional target(s) that regulate the apoptotic pathway in B-NHLs. Predictive analyses coupled with database-deposited data suggested that YY1 binds the promoter of the BIRC5/survivin anti-apoptotic gene. Gene Expression Omnibus (GEO) analyses of several B-NHL repositories revealed a conserved positive correlation between YY1 and survivin, both highly expressed, especially in aggressive B-NHLs. Further validation experiments performed in Raji Burkitt&rsquo, s lymphomas cells, demonstrated that YY1 silencing was associated with survivin downregulation and sensitized the cells to apoptosis. Overall, our results revealed that: (1) YY1 and survivin are positively correlated and overexpressed in B-NHLs, especially in BLs, (2) YY1 strongly binds to the survivin promoter, hence survivin may be suggested as YY1 transcriptional target, (3) YY1 silencing sensitizes Raji cells to drug-induced apoptosis via downregulation of survivin, (4) both YY1 and survivin are potential diagnostic markers and therapeutic targets for the treatment of resistant/relapsed B-NHLs.

The search for novel lipid A analogues from any biological source that can act as antagonists, displaying inhibitory activity towards the production of pro-inflammatory cytokines, or as immunomodulators in mammals, is a very topical issue. To this aim, the structure and immunological properties of the lipopolysaccharide lipid A from the purple nonsulfur bacterium Rhodopseudomonas palustris strain BisA53 have been determined. This lipid A displays a unique structural feature, with a non-phosphorylated skeleton made up of the tetrasaccharide Manp-α-(1→4)-GlcpN3N-β-1→6-GlcpN3N-α-(1→1)-α-GalpA, and four primary amide-linked 14:0(3-OH) and, as secondary O-acyl substituents, a 16:0 and the very long-chain fatty acid 26:0(25-OAc), appended on the GlcpN3N units. This lipid A architecture is definitely rare, so far identified only in the genus Bradyrhizobium. Immunological tests on both murine bone-marrow-derived and human monocyte-derived macrophages revealed an extremely low immunostimulant capability of this LPS lipid A.

The upper urinary tract is the most common human system affected by congenital anomalies. Congenital anomalies of the kidneys and ureters comprise a wide spectrum of disorders ranging from simple variants with no clinical significance to complex anomalies that may lead to severe complications and end-stage renal disease. They may be classified as anomalies of renal form, which are subclassified as structural anomalies (eg, persistent fetal lobulation, hypertrophied column of Bertin, and dromedary hump) and fusion anomalies (eg, horseshoe kidney and pancake kidney); anomalies of renal position (eg, renal malrotation, simple renal ectopia, and crossed renal ectopia) and renal number (eg, renal agenesis and supernumerary kidney); and abnormalities in development of the urinary collecting system (eg, pyelocaliceal diverticulum, megacalycosis, ureteropelvic junction obstruction, duplex collecting system, megaureter, ectopic ureter, and ureterocele). US is usually the first imaging modality used because of its low cost, wide availability, and absence of ionizing radiation. Intravenous urography and voiding cystourethrography are also useful, mainly for characterization of the collecting system and vesicoureteral reflux. However, intravenous urography has been replaced by CT urography and MR urography. These imaging methods not only allow direct visualization of the collecting system but also demonstrate the function of the kidneys, the vascular anatomy, adjacent structures, and complications. Comprehension of congenital anomalies of the upper urinary tract is crucial for an accurate diagnosis and correct management. The authors discuss the spectrum of these anomalies, with emphasis on embryologic development, imaging findings, clinical manifestations, and complications.

Chlamydophila pneumoniae is an intracellular pathogen responsible for respiratory tract infections. The isolation of the microorganism from clinical specimens is essential for a diagnosis. However, the identification of C. pneumoniae by cell cultures is very difficult besides strongly depending on the sample conditions. The study aimed to investigate, in adult patients with pharyngotonsillitis, the frequency of Chlamydophila pneumoniae detection by cell cultures and three conventional PCRs (a conventional PCR targeting the 16S rRNA gene and two nested PCRs, targeting the 16S rRNA gene and the ompA gene, respectively). The presence of chlamydial inclusion in cell cultures was observed in 11/94 samples (11.70%) by IFA. C. pneumoniae DNA was detected in 12/94 (12.76%) specimens by the 16S rRNA gene nested PCR, 4/94 (4.26%) by ompA gene nested PCR, and in 2/94 (2.13%) by 16S rRNA single-step PCR. Our data show poor agreement between the three applied DNA-amplification methods; in fact, only 16S rRNA gene nested PCR showed a statistically significant difference. Moreover, this result allowed us to achieve a definitive confirmation of the previous finding and to avoid the risk of an overestimation of the C. pneumoniae as a pathogen in pharyngotonsillitis.

CSF diagnostics has proved to be a formidable testing ground for N-glycoproteomic analysis of neurological diseases. To characterize specific N-glycan profiles of CSF in early and advanced phases of Alzheimer's disease, as well as in lysosomal storage disorders such as Tay-Sachs disease, we set up in our lab a robust and feasible protocol by coupling bioanalytical methods and mass spectrometry analysis.Starting from a few microliters of CSF, after protein denaturation, reduction, and alkylation, N-glycans are released from glycoproteins using the peptide-N-glycosidase F (PNGase F) and purified. The analysis of permethylated N-glycans by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and MALDI-TOF MS/MS allowed us to identify specific glyco-structures and also to distinguish between isobaric N-glycans.

Aim: Measles is one of the most infectious communicable diseases. The objective of this study was to determine the immunity to measles of healthcare workers (HCWs) operating in three hospitals of Catania. Methods: A total of 549 HCWs underwent measles screening. A 5 ml blood sample was taken from each worker to measure IgG antibody levels. Results: Overall seroprotection was 86%. Unvaccinated HCWs agreed to undergo the vaccination offered by the hospital. Furthermore, it was found that younger workers are less seroprotected than older ones. Conclusion: Model legislation may be helpful to countries wishing to implement immunization requirements in healthcare settings in order to virtually eliminate the risk of acquiring and spreading measles in healthcare settings.

Pathogenic de novo variants in the X-linked gene SLC35A2 encoding the major Golgi-localized UDP-galactose transporter required for proper protein and lipid glycosylation cause a rare type of congenital disorder of glycosylation known as SLC35A2-congenital disorders of glycosylation (CDG; formerly CDG-IIm). To date, 29 unique de novo variants from 32 unrelated individuals have been described in the literature. The majority of affected individuals are primarily characterized by varying degrees of neurological impairments with or without skeletal abnormalities. Surprisingly, most affected individuals do not show abnormalities in serum transferrin N-glycosylation, a common biomarker for most types of CDG. Here we present data characterizing 30 individuals and add 26 new variants, the single largest study involving SLC35A2-CDG. The great majority of these individuals had normal transferrin glycosylation. In addition, expanding the molecular and clinical spectrum of this rare disorder, we developed a robust and reliable biochemical assay to assess SLC35A2-dependent UDP-galactose transport activity in primary fibroblasts. Finally, we show that transport activity is directly correlated to the ratio of wild-type to mutant alleles in fibroblasts from affected individuals.

Purpose Membranous nephropathy (MN) is the most frequent cause of nephrotic syndrome in adults and the disease course is characterized by the "rule of third", with one-third of patients experiencing complete remission and the remaining experiencing relapses or progression of the disease. Additionally, the therapeutic approach is not standardized, leading to further heterogeneity in terms of response and outcome. Experimental design In this pilot study, MALDI-MSI analysis is performed on renal biopsies (n = 13) obtained from two homogeneous groups of patients, which differentially responded to the immunosuppressive treatments (Ponticelli regimen). Results A signal at m/z 1303 displays the greatest discriminatory power when comparing the two groups and is observed to be of higher intensity in the glomeruli of the non-responding patients. The corresponding tryptic peptide is identified as macrophage migration inhibitory factor (MIF). Conclusions and clinical relevance Despite much effort being made in recent years to understand the pathogenesis of MN, a biomarker able to predict the outcome of these patients following therapeutic treatment is still lacking. Here, a protein (MIF), verified by immunohistochemistry, that can differentiate between these MN patients and could be a valuable starting point for a further study focused on verifying its predictive role in therapy response is highlighted.

The structural characterization of the lipopolysaccharide (LPS) from extremophiles has important implications in several biomedical and therapeutic applications. The polyextremophile Gram-negative bacterium Halobacteroides lacunaris TB21, isolated from one of the most extreme habitats on our planet, the deep-sea hypersaline anoxic basin Thetis, represents a fascinating microorganism to investigate in terms of its LPS component. Here we report the elucidation of the full structure of the R-type LPS isolated from H. lacunaris TB21 that was attained through a multi-technique approach comprising chemical analyses, NMR spectroscopy, and Matrix-Assisted Laser Desorption Ionization (MALDI) mass spectrometry. Furthermore, cellular immunology studies were executed on the pure R-LPS revealing a very interesting effect on human innate immunity as an inhibitor of the toxic Escherichia coli LPS.

Background The soluble fraction of the CD44 protein (solCD44) may constitute a valuable biological marker of Cancer Stem Cells (CSCs), useful for screening/early detection of laryngeal cancer, and for the prognosis. In previous papers, in fact, we have studied the expression of salivary solCD44 in patients with laryngeal tumors, supporting its use for early diagnosis of laryngeal carcinoma with high sensitivity and specificity, also with prognostic role, useful for clinical outcome. Objective The purpose of present study was to verify the levels of solCD44 isoform v6, sCD44var (v6), in saliva samples of patients with laryngeal carcinoma in our tumoral biobank, to evaluate possible correlations with clinical-anamnestic and prognostic data. Methods Study design was retrospective. Salivary samples of 66 patients with laryngeal cancer recruited from January 2012 to December 2013 were selected from our tumoral biobank. For each salivary sample was performed the determination of solCD44 and its isoform v6, sCD44var (v6), by ELISA. Qualitative and quantitative results of the test were correlated with clinical and medical history data. For statistical analysis we used the software MedCalc (versione 12.2.1.0). Results Concentrations of salivary sCD44var v6 were significantly higher according to the size of the primary tumor (T) (p= 0.001), the tumor site glottic or supraglottic-transglottic (p= 0.005) and according to the metastatic lymph node involvement (p= 0005). Furthermore, tumors in advanced disease (stage III-IV) showed values of salivary sCD44var v6 higher than the tumors in early stage, with a statistically significant difference (p= 0.005). Conclusions The determination of the levels of salivary solCD44 v6 may represent a promising prognostic test in laryngeal carcinomas.

Poor adherence to treatment remains a major problem in the management of patients with schizophrenia. In the 60s, first generation antipsychotics in depot formulation have been introduced on the market with the aim to improve adherence to therapy. However, the limited effectiveness on negative symptoms and the tendency to induce extrapyramidal side effects has limited their use. Currently there are five second-generation antipsychotic long-acting formulations and the use of these drugs has definitely changed perspective: they are no more restricted as compounds intended to improve compliance, but they can be considered first-line drugs with proven efficacy and good tolerability. In this narrative review the efficacy and tolerability of paliperidone palmitate, as well as the economic impact of the use of this particular molecule, have been evaluated in the short- and long-term treatment of schizophrenia. Taking into account the results of different studies, paliperidone, especially in his long-acting formulation, can be considered a viable and effective treatment for patients with schizophrenia, both in the short- and in the long term.

Paliperidone is a second-generation antipsychotic drug belonging to the class of benzisoxasole derivatives. Paliperidone is the major active metabolite of risperidone (9-OH-risperidone) and, as such, is comparable to the latter in terms of pharmacodynamic properties. However, due to its peculiar characteristics, paliperidone may be particularly useful in the treatment of schizophrenic patients. In this critical review of the literature the efficacy and tolerability in the short- and in the long-term have been evaluated in patients with schizophrenia. Taking into account the tolerability and efficacy data, together with the use of innovative sustained-release formulation, with a peculiar pharmacokinetic profile that allows single daily administration, paliperidone can be considered a valid option both for the short and the long-term treatment of schizophrenia.

In this chapter, we present the methodology currently applied in our laboratory for the structural elucidation of the cerebrospinal fluid (CSF) N-glycome. N-glycans are released from denatured carboxymethylated glycoproteins by digestion with peptide-N-glycosidase F (PNGase F) and purified using both C18 Sep-Pak

To determine the relationship between multidetector computed tomography (MDCT) findings, management strategies, and ultimate clinical outcomes in patients with splenic injuries secondary to blunt trauma. This Institutional Review Board-approved study collected 351 consecutive patients admitted at the Emergency Department (ED) of a Level I Trauma Center with blunt splenic trauma between October 2002 and November 2015. Their MDCT studies were retrospectively and independently reviewed by two radiologists to grade splenic injuries according to the American Association for the Surgery of Trauma (AAST) organ injury scale (OIS) and to detect intraparenchymal (type A) or extraparenchymal (type B) active bleeding and/or contained vascular injuries (CVI). Clinical data, information on management, and outcome were retrieved from the hospital database. Statistical analysis relied on Student’s t, chi-squared, and Cohen’s kappa tests. Emergency multiphase MDCT was obtained in 263 hemodynamically stable patients. Interobserver agreement for both AAST grading of injuries and vascular lesions was excellent (k = 0.77). Operative management (OM) was performed in 160 patients (45.58% of the whole cohort), and high-grade (IV and V) OIS injuries and type B bleeding were statistically significant (p

IL-6 has a key role in the pathogenesis, clinical manifestations and activity of Systemic Onset Idiopathic Arthritis (sJIA). Tocilizumab (TCZ), the first humanized antihuman IL-6 receptor antibody, inhibits the activity of IL-6. In this review, we summarize the main studies performed, to date, about the use of TCZ in children affected by sJIA refractory to conventional treatment. Nowadays TCZ can be used, alone or in association with Metotrexate, in children older than 2 years. Its use in children younger than 2 years is being investigated. Further study about its use in sJIA and other type of idiopathic arthritis should be done.

Recent studies have suggested a possible correlation between obesity and adenovirus 36 (Adv36) infection in humans. As information on adenoviral DNA presence in human adipose tissue are limited, we evaluated the presence of Adv36 DNA in adipose tissue of 21 adult overweight or obese patients. Total DNA was extracted from adipose tissue biopsies. Virus detection was performed using PCR protocols with primers against specific Adv36 fiber protein and the viral oncogenic E4orf1 protein nucleotide sequences. Sequences were aligned with the NCBI database and phylogenetic analyses were carried out with MEGA6 software. Adv36 DNA was found in four samples (19%). This study indicates that some individuals carry Adv36 in the visceral adipose tissue. Further studies are needed to determine the specific effect of Adv36 infection on adipocytes, the prevalence of Adv36 infection and its relationship with obesity in the perspective of developing a vaccine that could potentially prevent or mitigate infection.

An environmental contamination due to an asbestiform mineral fiber, fluoro-edenite (FE), caused a significantly increased mortality rate for malignant mesothelioma in Biancavilla, Italy. Exposure to fluoro-edenite has been associated with inflammatory processes as an early response to inhaled fibers. The aim was to explore prevalence of anti-nuclear autoantibodies (ANA) in a group of construction workers residing and working in the contaminated area. Prevalences for samples positive to ANA were 60% (n = 9) and 13% (n = 2), for exposed and nonexposed, respectively (p-value

Background: A comprehensive look at health status in developmentally disabled populations shows poorer physical, oral, and vision health, and higher rates of heart disease and obesity. Generally, individuals with developmental disabilities have difficulty locating able providers, and face significant barriers in accessing health services. The health care system’s failure to achieve effective collaboration between medical, mental health, and residential providers too often results in substandard care and poor outcomes for these populations. Methods: A creative partnership between two organizations in rural upstate New York, Ulster Green ARC and the Institute for Family Health, has made substantial inroads toward addressing this problem. The organizations have transformed a relationship borne of a financially failing health care model into a successful, comprehensive care network for a severely developmentally disabled population-based in a Federally Qualified Health Center. Conclusions: The success of this effort is largely owing to an innovative use of health information technology to share information.

Congenital disorders of glycosylation (CDG) are due to defective glycosylation of glycoconjugates. Conserved oligomeric Golgi (COG)-CDG are genetic diseases due to defects of the COG complex subunits 1-8 causing N-glycan and O-glycan processing abnormalities. In COG-CDG, isoelectric focusing separation of undersialylated glycoforms of serum transferrin and apolipoprotein C-III (apoC-III) allows to detect N-glycosylation and O-glycosylation defects, respectively. COG5-CDG (COG5 subunit deficiency) is a multisystem disease with dysmorphic features, intellectual disability of variable degree, seizures, acquired microcephaly, sensory defects and autistic behavior. We applied matrix-assisted laser desorption/ionization-MS for a high-throughput screening of differential serum O-glycoform and N-glycoform in five patients with COG5-CDG. When compared with age-matched controls, COG5-CDG showed a significant increase of apoC-III

The aim of this paper is to report on our ample experience with the medial cord to musculocutaneous (MCMc) nerve transfer. The MCMc technique is a new type of neurotization which is able to reanimate the elbow flexion in multilevel avulsive injuries of the brachial plexus provided that at least the T1 root is intact. A series of 180 consecutive patients, divided into four classes according to the quality of hand function, is available for a long-term follow-up after brachial plexus surgery. The patients enrolled for the study have in common a brachial plexus palsy showing multiple cervical root avulsive injuries at two (C5-C6), three (C5-C6-C7) and four (C5-C6-C7-C8) levels. The reinnervation of the musculocutaneous nerve is obtained via an end-to-end transfer from two donor fascicles located in the medial cord. The selected fascicles are those directed principally to the flexor carpi radialis, ulnaris and, to a lesser degree, the flexor digitorum profundus. Under normal anatomic conditions, they are located in the medial cord, and their site corresponds to the inverted V-shaped bifurcation between the internal contribution of the median nerve and the ulnar nerve. The technique has no failure and no complications when the hand shows a normal wrist and finger flexion and a normal intrinsic function. In case of suboptimal conditions of the hand, the technique has proved technically more challenging, but still with 67 % satisfactory results. In the four-root avulsive injuries, however, this method shows its limitations and an alternative strategy should be preferred when possible. EMG analysis shows a reinnervation in both the biceps and the brachialis muscles, explaining the high quality of the observed results. Moreover, this technique theoretically offers the possibility of a “second attempt” at a more distal level in case of failure of the first surgery. This procedure is quick, safe, extremely effective and easily feasible by an experienced plexus surgeon. The ideal candidate is a patient harbouring a C5-C6 avulsive injury of the upper brachial plexus with a normally functioning hand.

Objective Chronic subdural hematoma (CSH) is a common neurosurgical disease among elderly population with concomitant degenerative neurological disorders. This is a retrospective series-control analysis of prospectively collected data, aiming to show advantages and indications of a minimally invasive, percutaneous drainage system for CSH. Patients and methods We retrospectively analyse the clinical and radiological data of a minimally invasive, percutaneous draining system (Integra ™) used in fifteen patients (Group A; mean age: 75.7) with CSH, and compare them with those obtained from two retrospective series of patients: the first one (Group B 15 patients, mean age 77.1) treated with standard, single-burr hole technique for subdural drainage under general anaesthesia; the second one (Group C 15 patients, mean age 76.4) treated with standard, single-burr hole technique for subdural drainage under local anaesthesia and mild sedation. All The percutaneous procedures (Group A) were performed under local anaesthesia. Results Mean follow-up was 10.9 (range 3–14), 18.2 (range 10–29) and 15.2 (range 8–28) months in Group A, B and C respectively. Three of 15 and in Group B experienced a worsening of pre-existing neurodegenerative disorders after general anaesthesia. One patient in group C suffering from Parkinson’s disease experienced a worsening of gait disturbances. Post-operative CT scans were performed at 48 h and 21 days after the operation. An early post-operative CT-scan, obtained immediately after surgical procedure, was performed in all Group A patients. No differences in CSH evacuation were observed comparing the three groups. Two recurrent hematomas, one in group A and one in group B, required revision. Post-operative hospitalization was similar (5.1 vs 5.7 vs 5.6 days, respectively, in group A, B and C) but analgesics use was lower in Group A. Conclusion Pre-operative evaluation of radiological features of CSDHs is crucial in determining the right indication for a minimally invasive drainage. Minimally invasive treatments of CSH may reduce the use of anaesthetic drugs and worsening of pre-existing neurodegenerative disorders.

The structure and the immunology of the lipopolysaccharide (LPS) of Pseudomonas entomophila, an entomopathogenic bacterium isolated from the fruit fly Drosophila melanogaster, was characterized. The O-antigen portion was established and resulted to be built up of a repetitive unit constituted by four monosaccharide residues, all L configured, all deoxy at C-6 and with an acetamido function at C-2: -> 3)-alpha-L-FucNAc-(1 -> 4)-alpha-L-FucNAc-(1 -> 3)-alpha-L-FucNAc-(1 -> 3)-beta-L-QuiNAc-(1 -> The structural analysis of lipid A, showed a mixture of different species. The diphosphorylated glucosamine backbone carries six fatty acids consistent with the composition C10:0 3(OH), C12:0 2(OH) and C12:0 3(OH), whereas other species differs by the number of phosphates and/or of fatty acids. The immunology experiments demonstrated that the LPS structure of P. entomophila displayed a low ability to engage the TLR4-mediated signaling correlated to a significant antagonistic activity toward hexa-acylated LPS structures. (C) 2015 Elsevier Ltd. All rights reserved.

Background The purpose of this study was to verify CD44sol levels in the saliva of patients during follow-up after surgery for laryngeal cancer, to compare them with those registered at the time of diagnosis (pre-intervention) in the same patients, and to assess the reliability of the test as a prognostic indicator. Methods This prospective study was performed on 21 patients having laryngeal cancer who underwent surgery at the Division of Otolaryngology, University of Catanzaro; twelve adults with head and neck benign disease were recruited to form a control group. For each patient, the clinical–anamnestic data were collected and entered into a database. The sampling of undiluted saliva was performed the day before surgery and during the follow-up, every 3 months. Salivary CD44sol levels were determined using the ELISA method. Results Mean salivary CD44sol levels in the patients group before surgery (pre-intervention) were significantly higher than those in the control group (70.75 ± 33.8 vs. 12.4 ± 8.7 ng/ml). At follow-up performed 3 months after surgery, 18 of 21 (85.71%) patients had a reduction in salivary CD44sol levels, with a mean value of 50.1 ng/ml; the difference between these and pre-intervention CD44sol levels was statistically significant (P

Health care workers (HCWs) are frequently exposed to different biological agents during their activities and are frequently monitored. Among these infectious agents, human hepatitis C (HCV) can infect HCWs. In this review article, the risk of HCV infection among HCWs is discussed along with extrahepatic HCV-related malignancies, such as non-Hodgkin lymphoma. Accidental contamination, represented by percutaneous and mucocutaneous infections is the main risk factor for such infection. The compliance of the protection procedures, included in the current regulation for HCWs, is the most important issue to reduce the risk of pathogen infections that in turn may produce reduction of infection-associated malignancies.

Thermomonas hydrothermalis is a Gram-negative thermophilic bacterium that is able to live at 50°C. This ability is attributed to chemical modifications, involving those to bacterial cell-wall components, such as proteins and (glyco)lipids. As the main component of the outer membrane of Gram-negative bacteria, lipopolysaccharides (LPSs) are exposed to the environment, thus they can undergo structural chemical changes to allow thermophilic bacteria to live at their optimal growth temperature. Furthermore, as one of the major target of the eukaryotic innate immune system, LPS elicits host immune response in a structure-dependent mode; thus the uncommon chemical features of thermophilic bacterial LPSs might exert a different biological action on the innate immune system-an antagonistic effect, as shown in studies of LPS structure-activity relationship in the ongoing research into antagonist LPS candidates. Here, we report the complete structural and biological activity analysis of the lipo-oligosaccharide isolated from Thermomonas hydrothermalis, achieved by a multidisciplinary approach (chemical analysis, NMR, MALDI MS and cellular immunology). We demonstrate a tricky and interesting structure combined with a very interesting effect on human innate immunity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

© 2017 Wiley Periodicals, Inc.We describe the clinical and whole genome sequencing (WGS) study of a non-consanguineous Italian family in which two siblings, a boy and a girl, manifesting a severe epileptic encephalopathy (EE) with skeletal abnormalities, carried novel SLC35A3 compound heterozygous mutations. Both siblings exhibited infantile spasms, associated with focal, and tonic vibratory seizures from early infancy. EEG recordings showed a suppression-burst (SB) pattern and multifocal paroxysmal activity in both. In addition both had quadriplegia, acquired microcephaly, and severe intellectual disability. General examination showed distal arthrogryposis predominant in the hands in both siblings and severe left dorso-lumbar convex scoliosis in one. WGS of the siblings-parents quartet identified novel compound heterozygous mutations in SLC35A3 in both children. SLC35A3 encodes the major Golgi uridine diphosphate N-acetylglucosamine transporter. With this study, we add SLC35A3 to the gene list of epilepsies. Neurological symptoms and skeletal abnormalities might result from impaired glycosylation of proteins involved in normal development and function of the central nervous system and skeletal apparatus.