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Abstract: An effective way of trapping phthalocyanines inside porous silica has been achieved when an aqueous solution of these macrocyclic species is reacted in situ with silicon alkoxide. The resultant porous gel network can encapsulate a myriad of metal phthalocyanine molecules at relatively high concentrations and, most importantly, in a disaggregated way. By employing this method metal sulfophthalocyanines of Fe, Co, Ni, Cu, Al, Eu or Sm can be encapsulated within SiO2 xerogels. Here, the chemical entrapment of phthalocyanines inside silica gel pore networks is accomplished by the attachment of bifunctional groups to the walls of these substrates; while one of these moieties is directly linked to the macrocycle end groups, the other one is covalently bonded to the silanol groups resting on the SiO2 walls. Furthermore, when the proper concentrations of phthalocyanine species, H2O, silicon alkoxide, and HCl are reacted together, it is possible to obtain monolithic translucent silica xerogels. This latter property provides straightforward evidence of the innate fluorescence of the trapped macrocycles. The average size of the cavities encapsulating the macrocyclic molecules range from 2.0 to 3.6nm; the precise size depends on the cation present in the complex and on the identity and position of the substituent groups at the periphery of the macrocycle. When the silica network is prepared from standard and/or organo-substituted alkoxides, the aggregation, degradation or stability of the macrocyclic species trapped in silica cavities depends on the nature of the alkyl group attached to the pore walls. [Copyright &y& Elsevier]

Abstract: Recurrent deletions of the 17q21.31 region encompassing the microtubule-associated protein tau (MAPT) gene have recently been described in patients with mental retardation. This region is flanked by segmental duplications that make it prone to inversions, deletions and duplications. Since gain-of-function mutations of the MAPT gene cause frontotemporal lobar degeneration (FTLD) characterized by deposition of tau protein, we hypothesize that MAPT duplication affecting gene dosage could also lead to disease. Gene dosage alterations have already been found to be involved in the etiology of neurodegenerative disorders caused by protein or peptide accumulation, such as Alzheimer''s and Parkinson''s diseases. To determine whether MAPT gene copy number variation is involved in FTLD, 70 patients with clinical diagnosis of FTLD and no MAPT mutation (including 12 patients with pathologically proven tau-positive FTLD) were screened by using multiplex ligation probe amplification (MLPA) with specific oligonucleotide probes. No copy number variation in the MAPT gene was observed in cases. Although our study was limited by the relatively small number of patients, it does not support the theory that chromosomal rearrangements in this region are a cause of FTLD. [Copyright &y& Elsevier]

Highlights • Although carcinoid accounts for only 1% of all the gastric tumors it is the most common type of neuroendocrine neoplasia of the stomach. • Its increased incidence among the obese population in relation to the general population. • Resective gastric bypass may be considered as a treatment of choice for patients who after bariatric surgery were diagnosed with gastric carcinoid and weight regain. Abstract Introduction Although carcinoid tumours are a rare gastrointestinal neoplasm with an incidence rate of 1–2.5 cases per 100 000 inhabitants, they are the most common neuroendocrine tumour of the stomach. Presentation of case A 70-year-old-man consulted for epigastric pain and dyspepsia symptoms. His past medical and surgical history included obesity (BMI: 53.9 kg/m2), hypertension, hyperlipidemia, diabetes mellitus type 2, cardiac failure and a surgical treatment with laparoscopic gastric banding. For the analysis and control of the gastric banding an upper gastrointestinal endoscopy was performed evidencing many small polyps in the gastric antrum, body and fundus. The histopathological examination of the resected specimen revealed a well differentiated carcinoid. Laparoscopic surgery for the removal of the gastric banding and the subtotal gastrectomy leaving a small gastric remnant of approximately 2-cm in size similar to the pouch of a bypass was done. Twelve months after surgery the patient presented a body mass index of 36.6 kg /m2. Discussion Gastric carcinoid increased incidence among the obese population, although the causing mechanisms are not clear, yet it is likely that metabolic and hormonal effects of the obesity play a role. The resection may be performed either endoscopically when the lesions are small, or surgically according to the tumor type and size. Conclusion The resective gastric bypass or gastrectomy with anastomosis by Roux- en- Y bypass may be considered as a treatment of choice for patients who after bariatric surgery were diagnosed with gastric carcinoid and weight regain. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2DM) is associated with alterations of the immune response and T2DM patients have an increased risk for infections and certain sorts of cancers. Although CD14+HLA-DR-/low cells have emerged as important mediators of immunosuppression in several pathologies, including cancer and non-malignant diseases, the presence of these cells in T2DM is not fully characterized. In this study, we evaluated the frequency of CD14+HLA-DR-/low cells in non-obese T2DM patients and their association with glycemic control. Peripheral blood mononuclear cells were isolated from healthy controls (HC, n = 24) and non-obese T2DM patients (n = 25), the population was evaluated by flow cytometry, and an analysis of correlation between cell frequencies and clinical variables was performed. CD14+HLA-DR-/low monocytes were expanded in patients with T2DM compared to HC regardless of weight. Among the subjects with T2DM, the frequency of CD14+HLA-DR-/low was higher in patients with poor glycemic control (HbA1c > 9%) compared to those with better glycemic control (HbA1c < 9%) and, positively correlated with the years since the diagnosis of T2DM, the age of the patients and the glycemic index. An increased frequency of CD14+HLA-DR-/low cells in the blood of T2DM patients was recorded. The influence of hyperglycemia seems to be independent of obesity, but related to glycemic control and age. [ABSTRACT FROM AUTHOR]

The implementation of Next Generation Sequencing, particularly exome sequencing (ES), into clinical practice has revolutionised the genetic diagnosis of rare diseases. However, it is estimated that 50% of patients with neuromuscular diseases remain undiagnosed after ES. Here, we evaluated total RNA sequencing (RNAseq) from muscle biopsies as a diagnostic tool in genetically unsolved patients. Total RNAseq was extracted from muscle biopsies of 54 undiagnosed patients after ES or gene panel sequencing, 3 positive controls (patients with previously identified RNA defects in the DMD gene) and 17 healthy controls. We evaluated the presence of aberrant splicing, outlier gene expression and allelic imbalance in autosomal recessive genes. In addition, variant calling was performed from the RNAseq data. In 7/54 patients (12.9%) we detected pathogenic alterations at the mRNA level, including two exon skipping events (COL6A1), one intronic retention (TTN), one alternative splicing caused by a synonymous variant (RYR1), one pseudoexon (DMD) and two patients with allelic imbalance in an autosomal recessive gene (GNE). In one of these cases, WGS was required to achieve the genetic diagnosis. Three patients (5.55%) remain under investigation due to the detection of alternative splicing events in new candidate genes. In addition, reanalysis of existing ES data allowed the diagnosis of 8/54 individuals (14.8%). In this study, we show that RNAseq analysis improves the diagnostic rate in patients with neuromuscular diseases after inconclusive results in ES. RNAseq not only enables the identification of molecular events that would not have been detected by other methods, but also allows the reclassification of VUS variants identified at the gDNA level. We also highlight the importance of a periodic reanalysis of existing genomic data and the utility of an integrated genomic and transcriptomic analysis. [ABSTRACT FROM AUTHOR]

• Antimicrobial peptides (AMPs) of domestic animals have beneficial effects on immune regulation, microbiota, and nutrition. • AMP have an important function in reproductive processes. • AMPs have been proposed in veterinary medicine as vaccine adjuvants, immunomodulators and dietary supplements. Antimicrobial peptides (AMPs) are molecules with a broad-spectrum activity against bacteria, fungi, protozoa, and viruses. These peptides are widely distributed in insects, amphibians and mammals. Indeed, they are key molecules of the innate immune system with remarkable antimicrobial and immunomodulatory activity. Besides, these peptides have also shown regulatory activity for gut microbiota and have been considered inductors of growth performance. The current review describes the updated findings of antimicrobial peptides in domestic animals, such as bovines, goats, sheep, pigs, horses, canines and felines, analyzing the most relevant aspects of their use as potential therapeutics and their applications in Veterinary medicine. [ABSTRACT FROM AUTHOR]

Aims: Monocytes and macrophages express cell-surface markers indicative of their inflammatory and activation status. In this study, we investigated whether these markers are affected or correlated in non-obese T2D subjects, or glycemic/metabolic control variables.Methods: Clinical data was recorded, and peripheral blood drawn from T2D patients (n = 28) and control subjects (n = 27). Isolated monocytes were evaluated by flow cytometry for the expression of CD14, CD16, and the phenotypic markers for the different states of activation spectrum, such as pro-inflammatory (M1) (HLA-DR, CD86), anti-inflammatory/pro-resolving (M2) (CD163, CD206, MERTK, PD-L1) and metabolically-activated (MMe) (CD36, ABCA-1). From a subset of individuals, monocytes-derived macrophages (MDM) were obtained and evaluated for phenotypic markers. A correlation analysis was performed between the clinical variables and the marker expression.Results: The frequency of CD14++CD16- monocytes was lower in T2D patients and it correlates negatively with poor control in glycemic and metabolic variables. T2D monocytes expressed lower levels of HLA-DR, CD86, PD-L1, and CD163, which correlated negatively with poor metabolic control. In MDM from T2D patients, HLA-DR, CD86 and CD163 expression was lower and it inversely correlated with deficient glycemic or metabolic control parameters.Conclusion: The glycemic/metabolic control associated with T2D influences monocyte and MDM phenotypes toward an immune-suppressive phenotype. [ABSTRACT FROM AUTHOR]