3d modelling of archaeological small finds by a low-cost range camera. Methodology and first results

The production of reliable documentation of small finds is a crucial process during archaeological excavations. Range cameras can be a valid alternative to traditional illustration methods: they are veritable 3D scanners able to easily collect the 3D geometry (shape and dimensions in metric units) of an object/scene practically in real-time. This work investigates precisely the potentialities of a promising low-cost range camera, the Structure SensorTM by Occipital, for rapid modelling archaeological objects. The accuracy assessment was thus performed by comparing the 3D model of a Cipriot-Phoenician globular jug captured by this device with the 3D model of the same object obtained through photogrammetry. In general, the performed analysis shows that Structure Sensor is capable to acquire the 3D geometry of a small object with an accuracy comparable at millimeter level to that obtainable with the photogrammetric method, even though the finer details are not always correctly modelled. The texture reconstruction is instead less accurate. In the end, it can be concluded that the range camera used for this work, due to its low-cost and flexibility, is a suitable tool for the rapid documentation of archaeological small finds, especially when not expert users are involved

Nutritional factors influencing plasma adiponectin levels: results from a randomised controlled study with whole-grain cereals

Data from intervention studies about the effects of a high intake of whole-grain cereals on adiponectin expression are still inconclusive. We evaluated the effects of whole-grain or refined cereals on fasting and postprandial serum adiponectin in people at high cardiovascular risk. According to a randomised controlled parallel group design, participants with metabolic syndrome were assigned to an isoenergetic diet based on either whole-grain cereal (WGC) or refined cereal (RC) products for 12-weeks. Anthropometric and biochemical measures were taken. Compared to baseline, fasting and postprandial serum adiponectin levels increased after both RC and WGC. In the WGC and RC groups combined, adiponectin concentrations significantly increased after 12-week intervention, and are directly associated with plasma SCFAs and acetate. Only increasing whole-grain cereals may not influence adiponectin levels, which could be modified by a fibre rich, low-fat, low-glycemic index diet, possibly through changes in gut microbiota, as suggested by the relation with SCFAs. Clinical Trials number: NCT00945854

Case Report: Concurrent Resistance and Aerobic Training Regulate Adiponectin Expression and Disease Severity in Multiple Sclerosis: A Case Study

Adapted exercise is an effective non-pharmacological tool to improve functional, cognitive, and psychological parameters in multiple sclerosis (MS), in association with increased quality of life (QoL) and decreased disease severity. Adipose tissue, through the production of different adipokines, is involved in regulating energy metabolism and inflammation. Adiponectin, increased in MS, circulates as oligomers of low (LMW), medium (MMW), and high molecular weight (HMW), the latter mediating the main biological effects. The aim of study was to evaluate the effects of 4 months training at moderate intensity [65% heart rate reserve (HRR)] on BMI, adiponectin, and QoL in a volunteer with secondary progressive MS. The parameters were evaluated before (T0), after 4 months training (T1), and 6 months after the end of training (T2); total serum adiponectin and its oligomeric profile were evaluated. We found a reduction in BMI (-0.9%) and FAT (-2.6%), an improvement in perceived QoL and a reduced expression of total adiponectin and HMW oligomers together with decreased MS disability level at T1 measured by EDSS. Despite the limitations of a case study, this represent a starting point to understand the influence of exercise in MS and the relationship with adiponectin expression

Short-Term Physiological Effects of a Very Low-Calorie Ketogenic Diet: Effects on Adiponectin Levels and Inflammatory States

Adipose tissue is a multifunctional organ involved in many physiological and metabolic processes through the production of adipokines and, in particular, adiponectin. Caloric restriction is one of the most important strategies against obesity today. The very low-calorie ketogenic diet (VLCKD) represents a type of caloric restriction with very or extremely low daily food energy consumption. This study aimed to investigate the physiological effects of a VLCKD on anthropometric and biochemical parameters such as adiponectin levels, as well as analyzing oligomeric profiles and cytokine serum levels in obese subjects before and after a VLCKD. Twenty obese subjects were enrolled. At baseline and after eight weeks of intervention, anthropometric and biochemical parameters, such as adiponectin levels, were recorded. Our findings showed a significant change in the anthropometric and biochemical parameters of these obese subjects before and after a VLCKD. We found a negative correlation between adiponectin and lipid profile, visceral adipose tissue (VAT), C-reactive protein (CRP), and pro-inflammatory cytokines such as tumor necrosis factor-a (TNF-a), which confirmed the important involvement of adiponectin in metabolic and inflammatory diseases. We demonstrated the beneficial short-term effects of a VLCKD not only in the treatment of obesity but also in the establishment of obesity-correlated diseases

Physical activity and sport performance: adiponectin in relation to different physio-pathological status

Adiponectin (Acrp30), and in particular its High Molecular Weight (HMW) oligomers, contributes to enhance insulin sensitivity and to reduce inflammation levels. Physical exercise improves body’s biochemical balance and metabolism resulting effective in the prevention and therapy of metabolic diseases. Whether improvement of metabolic features mediated by physical exercise is associated with changes in Acrp30 serum composition is not yet clarified. In the present study, we investigated total Acrp30 expression and its oligomeric status in two different metabolic status: professional Water Polo (WP) Players and adult patients affected by Cystic Fibrosis (CF) that performed regular physical exercise. CF is an inherited metabolic disease characterized by alterations in lipid and glucidic metabolism. Our results demonstrated significant elevated BMI, AST and LDH levels and, conversely, significantly lower concentrations of total cholesterol and VLD were present in WP players. No significant difference was found in total Acrp30 and/or HMW oligomers. Interestingly, in WP players, a direct relationship between total Acrp30 and monocytes as well as an inverse relationship between total Acrp30 and AST levels were found. ACDC molecular screening revealed previously described SNPs. In CF patients, physical exercise has significant effects on lipid and glycemic metabolism. Indeed, patients that performed exercise are characterized by significant decrease of either VLDL, cholesterol and triglycerides, border-line significant decrease of either total cholesterol/HDL and non-HDL cholesterol/HDL ratio and by trend decrease of total, LDL and non-HDL cholesterol, although not significant. It’s to highlight that physical exercise significantly reduces glycemia and HOMA-IR and increases serum albumin. However, physical exercise does not modify Acrp30 concentrations that, on the other hand, result significantly higher in all CF patients compared to controls. In conclusion, even if peripheral muscle abnormalities and respiratory factors limit exercise in patients with CF, our study indicated that physical activity has beneficial effects on lipid and glycemic metabolism in these patients not associated with Acrp30

372. Prevalence of Anti-AAV8 Neutralizing Antibodies and ARSB Cross-Reactive Immunologic Material in MPS VI Patients Candidates for a Gene Therapy Trial

Recombinant vectors based on adeno-associated virus serotype 8 (AAV8) have been successfully used in the clinic and hold great promise for liver-directed gene therapy. Pre-existing immunity against AAV8 or the development of antibodies against the therapeutic transgene product might negatively affect the outcomes of gene therapy. In the prospect of an AAV8-mediated, liver-directed gene therapy clinical trial for Mucopolysaccharidosis VI (MPS VI), a lysosomal storage disorder due to arylsulfatase B (ARSB) deficiency, we investigated in a multiethnic cohort of MPS VI patients the prevalence of neutralizing antibodies (Nab) to AAV8 and the presence of ARSB cross-reactive immunologic material (CRIM), which will either affect the efficacy of gene transfer or the duration of phenotypic correction. Thirty-six MPS VI subjects included in the study harbored 45 (62.5%) missense, 13 (18%) nonsense, 9 (12.5%) frameshift (2 insertions and 7 deletions), and 5 (7%) splicing ARSB mutations. To the best of our knowledge, four mutations had not been previously described. These include: one missense (c.1178 A>G p.H393R) and three frameshift mutations [883-884duplTT (p.F295FfsX42), c.1036delG (p.E346SfsX11), c.1475delC (pP492LfsX80)] predicted to result in truncated proteins. The detection of ARSB protein in twenty-four patients out of 34 (71%) was predicted by the type of mutations. Pre-existing Nab to AAV8 were undetectable in 19/33 (58%) analyzed patients. Twelve out of 31 patients (39%) tested were both negative for Nab to AAV8 and CRIM-positive. In conclusion, this study allows estimating the number of MPS VI patients eligible for a gene therapy trial by intravenous injections of AAV8

Nemaline Myopathy in Brazilian Patients: Molecular and Clinical Characterization

Nemaline myopathy (NM), a structural congenital myopathy, presents a significant clinical and genetic heterogeneity. Here, we compiled molecular and clinical data of 30 Brazilian patients from 25 unrelated families. Next-generation sequencing was able to genetically classify all patients: sixteen families (64%) with mutation in NEB, five (20%) in ACTA1, two (8%) in KLHL40, and one in TPM2 (4%) and TPM3 (4%). In the NEB-related families, 25 different variants, 11 of them novel, were identified; splice site (10/25) and frame shift (9/25) mutations were the most common. Mutation c.24579 G>C was recurrent in three unrelated patients from the same region, suggesting a common ancestor. Clinically, the “typical” form was the more frequent and caused by mutations in the different NM genes. Phenotypic heterogeneity was observed among patients with mutations in the same gene. Respiratory involvement was very common and often out of proportion with limb weakness. Muscle MRI patterns showed variability within the forms and genes, which was related to the severity of the weakness. Considering the high frequency of NEB mutations and the complexity of this gene, NGS tools should be combined with CNV identification, especially in patients with a likely non-identified second mutation

Nemaline Myopathy in Brazilian Patients: Molecular and Clinical Characterization

Nemaline myopathy (NM), a structural congenital myopathy, presents a significant clinical and genetic heterogeneity. Here, we compiled molecular and clinical data of 30 Brazilian patients from 25 unrelated families. Next-generation sequencing was able to genetically classify all patients: sixteen families (64%) with mutation in NEB, five (20%) in ACTA1, two (8%) in KLHL40, and one in TPM2 (4%) and TPM3 (4%). In the NEB-related families, 25 different variants, 11 of them novel, were identified; splice site (10/25) and frame shift (9/25) mutations were the most common. Mutation c.24579 G>C was recurrent in three unrelated patients from the same region, suggesting a common ancestor. Clinically, the “typical” form was the more frequent and caused by mutations in the different NM genes. Phenotypic heterogeneity was observed among patients with mutations in the same gene. Respiratory involvement was very common and often out of proportion with limb weakness. Muscle MRI patterns showed variability within the forms and genes, which was related to the severity of the weakness. Considering the high frequency of NEB mutations and the complexity of this gene, NGS tools should be combined with CNV identification, especially in patients with a likely non-identified second mutation

Therapeutic homology-independent targeted integration in retina and liver

Challenges to the widespread application of gene therapy with adeno-associated viral (AAV) vectors include dominant conditions due to gain-of-function mutations which require allele-specific knockout, as well as long-term transgene expression from proliferating tissues, which is hampered by AAV DNA episomal status. To overcome these challenges, we used CRISPR/Cas9-mediated homology-independent targeted integration (HITI) in retina and liver as paradigmatic target tissues. We show that AAV-HITI targets photoreceptors of both mouse and pig retina, and this results in significant improvements to retinal morphology and function in mice with autosomal dominant retinitis pigmentosa. In addition, we show that neonatal systemic AAV-HITI delivery achieves stable liver transgene expression and phenotypic improvement in a mouse model of a severe lysosomal storage disease. We also show that HITI applications predominantly result in on-target editing. These results lay the groundwork for the application of AAV-HITI for the treatment of diseases affecting various organs