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Fecal calprotectin (FC) has emerged as one of the most useful tools for clinical management of inflammatory bowel diseases (IBD). Many different methods of assessment have been developed and different cut-offs have been suggested for different clinical settings. We carried out a comprehensive literature review of the most relevant FC-related topics: the role of FC in discriminating between IBD and irritable bowel syndrome (IBS) and its use in managing IBD patients In patients with intestinal symptoms, due to the high negative predictive value a normal FC level reliably rules out active IBD. In IBD patients a correlation with both mucosal healing and histology was found, and there is increasing evidence that FC assessment can be helpful in monitoring disease activity and response to therapy as well as in predicting relapse, post-operative recurrence or pouchitis. Recently, its use in the context of a treat-to-target approach led to a better outcome than clinically-based therapy adjustment in patients with early Crohn's disease. In conclusion, FC measurement represents a cheap, safe and reliable test, easy to perform and with a good reproducibility. The main concerns are still related to the choice of the optimal cut-off, both for differentiating IBD from IBS, and for the management of IBD patients.

Background Few data exist regarding the effectiveness of ustekinumab in inflammatory bowel disease (IBD) patients treated for concomitant psoriasis or psoriatic arthritis. Aims to describe the outcomes of IBD patients who received subcutaneous ustekinumab through a dermatological or rheumatological prescription. Methods This multicenter, retrospective study included all IBD patients who were started on ustekinumab for concomitant active psoriasis/ psoriatic arthritis, irrespective of IBD activity. The primary endpoint was overall ustekinumab persistence, defined as the maintenance of therapy because of sustained clinical benefit for IBD. Results Seventy patients (64 Crohn’s disease / 6 ulcerative colitis) were enrolled. The median follow-up on ustekinumab therapy was 10.7 months (range, 1.4–67.3). Twelve patients (17.1%) withdrew the treatment after a median of 7.4 months (range, 0.9–23.8). The cumulative probability of maintaining ustekinumab treatment was 97.1% at 6 months and 77.1% at 12 months. Among the 56 patients with baseline active IBD, 34 (60.7%) were in clinical remission at the last follow-up visit. Their cumulative probability of achieving clinical remission was 84.7% and 63.9% at 6 and 12 months, respectively. Two patients stopped ustekinumab for an adverse event. Conclusions Subcutaneous ustekinumab had a good effectiveness profile for IBD patients treated for concomitant dermatological or rheumatological conditions.

Considerazioni critiche intorno all'uso della categoria dell'innovazione sociale

This article presents the use of caprylic acid (CA) to precipitate impurities from the protein A capture column elution pool for the purification of monoclonal antibodies (mAbs) with the objective of developing a two chromatography step antibody purification process. A CA-induced impurity precipitation in the protein A column elution pool was evaluated as an alternative method to polishing chromatography techniques for use in the purification of mAbs. Parameters including pH, CA concentrations, mixing time, mAb concentrations, buffer systems, and incubation temperatures were evaluated on their impacts on the impurity removal, high-molecular weight (HMW) formation and precipitation step yield. Both pH and CA concentration, but not mAb concentrations and buffer systems, are key parameters that can affect host-cell proteins (HCPs) clearance, HMW species, and yield. CA precipitation removes HCPs and some HMW species to the acceptable levels under the optimal conditions. The CA precipitation process is robust at 15-25°C. For all five mAbs tested in this study, the optimal CA concentration range is 0.5-1.0%, while the pH range is from 5.0 to 6.0. A purification process using two chromatography steps (protein A capture column and ion exchange polishing column) in combination with CA-based impurity precipitation step can be used as a robust downstream process for mAb molecules with a broad range of isoelectric points. Residual CA can be effectively removed by the subsequent polishing cation exchange chromatography.

Quali competenze per affrontare la crisi del paese da parte degli urbanisti ?

Cleaning-in-place (CIP) for column chromatography plays an important role in therapeutic protein production. A robust and efficient CIP procedure ensures product quality, improves column life time and reduces the cost of the purification processes, particularly for those using expensive affinity resins, such as MabSelect protein A resin. Cleaning efficiency, resin compatibility, and facility compatibility are the three major aspects to consider in CIP process design. Cleaning MabSelect resin with 50mM sodium hydroxide (NaOH) along with 1M sodium chloride is one of the most popular cleaning procedures used in biopharmaceutical industries. However, high concentration sodium chloride is a leading cause of corrosion in the stainless steel containers used in large scale manufacture. Corroded containers may potentially introduce metal contaminants into purified drug products. Therefore, it is challenging to apply this cleaning procedure into commercial manufacturing due to facility compatibility and drug safety concerns. This paper reports a safe, effective and environmental and facility-friendly cleaning procedure that is suitable for large scale affinity chromatography. An alternative salt (sodium sulfate) is used to prevent the stainless steel corrosion caused by sodium chloride. Sodium hydroxide and salt concentrations were optimized using a high throughput screening approach to achieve the best combination of facility compatibility, cleaning efficiency and resin stability. Additionally, benzyl alcohol is applied to achieve more effective microbial control. Based on the findings, the recommended optimum cleaning strategy is cleaning MabSelect resin with 25 mM NaOH, 0.25 M Na2SO4 and 1% benzyl alcohol solution every cycle, followed by a more stringent cleaning using 50 mM NaOH with 0.25 M Na2SO4 and 1% benzyl alcohol at the end of each manufacturing campaign. A resin life cycle study using the MabSelect affinity resin demonstrates that the new cleaning strategy prolongs resin life time and consistently delivers high purity drug products.

Introduction: Sleep problems are common in all ages, but may be particularly acute in urban Singapore. This study aims to describe the sleep behaviour of, and to identify any sleep problems in, preschool children. Materials and Methods: This was a cross-sectional questionnaire survey of 372 children attending local childcare centers. The questionnaire was based on the Children’s Sleep Habits Questionnaire (CSHQ), a validated parent-report sleep screening questionnaire that contains 54 items identifying sleep behaviours in children. Results: A total of 372 (40.0%) children participated. The mean age was 4.1 (SD 1.3) years (range, 2 to 6 years). Average total sleep duration was 10.8 hours (SD 1.1) with average night-time sleep duration of 8.5 hours (SD 0.6) and average nap duration of 1.6 hours (SD 1.0). Co-sleeping was common; 80.9% of children shared a room with someone else. The most common sleep problems were in the domains of sleep resistance and morning behaviour; namely: requiring company to fall asleep (n = 272, 73.1%), being afraid to sleep alone (n = 228, 61.6%) and difficulty in waking up (n = 165, 44.4%). Among parents, 84.1 % (n = 313) perceived that their child’s sleep duration was adequate. Conclusion: The duration of sleep in the Singaporean preschool population sampled is significantly lower than recommended values and that of previously described Caucasian populations. Parental perception of sleep adequacy deviates from current recommendations. Given the clear relation of sleep duration with cognitive functioning, learning, and physical growth, this sleep deprivation should be addressed with parental education and opportunistic screening of sleep in well-child follow-ups. Key words: Co-sleeping, Sleep duration, Sleep resistance

This study analyzed the relationship between Helicobacter pylori infection, mucosal gastrin concentration, and basal serum gastrin levels in duodenal ulcer patients with dyspepsia. Patients with duodenal ulcers who were H pylori positive showed higher antral gastrin concentrations than either H pylori-positive patients with dyspepsia or H pylori-negative patients with duodenal ulcers. No correlation was found between serum gastrin and antral gastrin concentrations. The increased antral gastrin concentrations were not correlated with an inhibition of acid-gastrin feedback. These preliminary data confirm that H pylori infection impairs gastrin physiology.

Genetic factors, particularly group A pepsinogen (PGA) and certain blood groups, seem to play a considerable part in the heterogeneity of ulcer disease, especially with regard to duodenal ulcer. The aim of this study was to evaluate serum PGA levels both in patients with duodenal ulcer and in various family members, thereby confirming possible correlations between duodenal ulcer and membership in a given blood group. Serum PGA levels were found to be higher in duodenal ulcer patients than in control subjects, whereas relatives of ulcer carriers had intermediate levels. Belonging to any given blood group did not influence PGA levels in the three groups considered. Blood groups and PGA may therefore be considered separate subclinical markers for peptic ulcer, although further prospective studies are warranted before PGA is to be considered as a prognostic marker for the onset of ulcer disease in healthy individuals.

Objectives: The aim of this study was to select and provide enough stem cells for quick transplantation in bone engineering procedures, avoiding any in vitro expansion step. Materials and Methods: Dental germ pulp, collected from 25 healthy subjects aged 13–20 years, were subjected to magnetic‐activated cell sorting to select a CD34(+) stem cell population capable of differentiating into pre‐osteoblasts. These cells were allowed to adhere to an absorbable polylactic–coglycolic acid scaffold for 30 min, without any prior expansion, and the CD34(+) cell‐colonized scaffolds were then transplanted into immunocompromised rats, subcutaneously. Results: After 60 days, analysis of recovered transplants revealed that they were formed of nodules of bone, of the same dimensions as the original scaffold. Bone‐specific proteins were detected by immunofluorescence, within the nodules, and X‐ray diffraction patterns revealed characteristic features of bone. In addition, presence of platelet endothelial cell adhesion molecule and von Willebrand factor immunoreactivity were suggestive of neo‐angiogenesis and neovasculogenesis taking place within nodules. Importantly, these vessels were HLA‐1(+) and, thus, clearly human in origin. Conclusions: This study indicates that CD34(+) cells obtained from dental pulp can be used for engineering bone, without the need for prior culture expanding procedures. Using autologous stem cells, this schedule could be used to provide the basis for bone regenerative surgery, with limited sacrifice of tissue, low morbidity at the collection site, and significant reduction in time needed for clinical recovery.

Il contributo ha l'obiettivo di mostrare, attraverso l'analisi critica di due casi clinici, una nuova tecnica chirurgica per il trattamento dei difetti infraossei parodontali; tecnica innovativa in quanto unisce e sovrappone le caratteristiche della chirurgia ricostruttiva a quella muco-gengivale. Le peculiarità del lembo singolo posizionato coronalmente (CP-SFA) sono quelle di poter scollare un lembo da un solo versante e di utilizzare un ancoraggio coronale stabile grazie alle papille disepitelizzate. I vantaggi derivanti da questa tecnica chirurgica sono il miglioramento dell'estetica parodontale, grazie alla limitazione della contrazione post-chirurgica, e un minor disagio postoperatorio da parte del paziente, grazie alla riduzione dell'area chirurgica. Questo tecnicismo può essere utilizzato quando l'estensione del o dei difetti infraossei sia confinata su di un unico versante, quando è presente un'area interprossimale integra adiacente a ogni difetto e quando la visibilità permette un'adeguata detersione del difetto e della superficie radicolare interessata. Nonostante gli ottimi esiti preliminari qui illustrati solamente un'ulteriore e rigorosa analisi scientifica potrà validare la tecnica proposta.

Objectives: Recent data indicate that low esophageal baseline impedance (BI) measurements may reflect the status of the esophageal mucosa. We aimed to correlate the first 30-min baseline impedance (BI) levels with the 24-h BI values in patients with heartburn and negative endoscopy. Moreover, we correlated those values with the results of 24-h impedancepH.Methods: Sixty patients with heartburn and negative endoscopy underwent 24-h impedance-pH testing off-therapy and were sub-categorized in: a) patients with abnormal acid exposure time (AET) and/or number of refluxes (NERD); b) patients with pathophysiological characteristics related to functional heartburn (FH). Impedance-pH tracks were manually evaluated to assess the mean 24-h BI (15-min time window for each hour, avoiding refluxes and swallowing) and the first 30-min BI after the placement of the probe. Moreover, AET, number of refluxes and symptom/reflux correlation (SAP) were measured. Results: NERD showed a higher mean AET (6.3±1.6% vs 0.6±0.3%, p

Squamous cell carcinoma (SCC), the most frequent malignant tumor of the oral cavity, generally exhibits a poor prognosis and metastases are the main cause of death. This tumor often arises from pre-malignant lesions. To date, it is difficult to predict if and which pre-malignant lesions may progress into oral SCC using traditional methods. For these reasons, several studies are trying to identify markers useful in the progression of pre-malignant lesions and tumors. To define the genetic expression profile of tongue tumor progression we compared 9 dysplasias (DS), 8 tumors without metastasis (TWM), 11 metastasizing SCCs (MT) of the tongue, and a baseline of 11 normal tissues by using cDNA microarray containing 19.2 K clones. We initially applied hierarchical agglomerative clustering based on information from all 6026 clones. Results were obtained by performing a two steps analysis: a Significance Analysis of Microarray (SAM) and a Gene Ontology search. One hundred and five clones have statistically significant different expression levels (FDR

Introduction: Problem of Abstraction of such an independent nosological form as non-alcoholic fatty disease of the pancreas has beenwidely debated in the past few years (M. M. Smits, 2011). Aims: To study the frequency of combination of non-alcoholic fatty disease of the liver and pancreas according to the results of computed tomography. Patients & methods: 180 patients with obesity were examined. All patients underwent computed tomography with an assessment of the organs’ density pursuant to the Hounsfield scale. Presence of fatty infiltration of both organs was determined upon the identification of hypodensia. Other computer-tomographic signs of steatosis of the liver and pancreas were also taken into consideration, particularly, steatosis of the pancreas was accompanied by a lobulation and certain lack of clarity of its structure. Density of the pancreas in the regions of its head, body and tail was determined. Results: Combination of steatosis of the liver and pancreas was detected in 126 (70.0%) patients. Steatosis of the pancreas in conjunction with a normal density of the liver was detected in 45 (25.0%) patients according to the results of computed tomography. The rarest variant that presupposed steatosis of the liver upon the absence of fatty infiltration of the pancreas was diagnosed in 9 (5.0%) patients. Significant differences of the densitometric density of the pancreas in its head, body and tail were not found. Conclusion: In the majority of cases, both steatosis of the liver and steatosis of the pancreas are developing in patients with metabolic syndrome.

This is a case study on the problems faced by third world immigrants in Europe, using the example of housing problems experienced by immigrants from north Africa to Naples, Italy.

The analysis of etiopathogenetic and clinical aspects of burning mouth syndrome, allow to suppose the participation of more factors in the determinism of disease. Consequently, also the therapy, might to require the presence of many specialist.

The AA. examine the current understanding of various aspects of the theories about cell origin, ultrastructural features and mechanism (one-cell or two-cell) of bone degradation of the osteoclasts The AA. examine the current understanding of various aspects of the theories about cell origin, ultrastructural features and mechanism (one-cell or two-cell) of bone degradation of the osteoclasts.