Managing chronic disease in the COVID-19 pandemic: an e-learning application to promote a healthy lifestyle for persons with multiple sclerosis.

E-health applications can support continuing care for persons with chronic diseases such as multiple sclerosis (MS). We have developed a web-based mobile app called VIOLA to be used at home by persons with MS (pwMS) who previously participated in an innovative multidisciplinary rehab program. The purpose of VIOLA is to reinforce what participants have learned about a healthy lifestyle and to keep them motivated to adhere to rehabilitation programs. As the outbreak of the Covid-19 pandemic has severely curtailed pwMS contact with their usual health providers, we quickly updated VIOLA to grant continuity of care to our home-bound patients.By monitoring pwMS subscriptions to individual modules, we found a definite increase after the national lockdown was declared. Subscribers rated the app very positively.Encouraged by the positive feedbacks, we are planning to extend the access to our app also to pwMS with no prior specific learning experience. This would limit the psychophysical consequences of the lockdown. Furthermore, VIOLA could be effective in maintaining a proper lifestyle, contributing to improve the quality of life of pwMS.VIOLA has the potential of increasing the adherence of pwMS to the rehabilitation confirming that digital communication tools are a valuable solution for those home-bound.].

A novel mutation in GCK gene: Beware of SGA child with diabetic mother.

MODY is a monogenic, autosomal dominant form of diabetes mellitus. MODY can be caused by mutations in several genes; glucokinase (GCK) accounts for 30-50% of the cases. The diagnosis can be suspected in early-onset diabetes with atypical features for type 1/type 2. Treatment is usually not recommended. A 5-year-old girl came to our attention for occasional episodes of hyperglycaemia. She was born at term, her birth weight was small for gestational age. At the beginning of her pregnancy, her mother was already on insulin therapy for impaired fasting glucose levels, detected before conception and confirmed in the first weeks of gestation. She was treated with insulin until the childbirth without further investigations. The patient was asymptomatic and in good clinical condition. Basal blood tests have shown a fasting plasma glucose of 125 mg/dl, an HbA1c of 6.5%. Antibodies against islet cells, anti-GAD and anti-ZNT8 antibodies were all negative. A 2-h oral glucose tolerance test was performed and underlined an impaired glucose tolerance. HLA haplotypes were screened, excluding susceptibility. GCK Sanger Sequencing identified a novel heterozygous variant. It is not described as a classical mutations. The analysis has been extended to the parents, finding out the same variant in her mother. To our knowledge this mutation has not been described previously; we believe that this variant is responsible for MODY2 due to FBG and Hb1Ac of all the affected members of family. We suggest high suspicion of an underlying GCK variant in SGA children with hyperglycaemia born to a diabetic mother.

Effect of Sildenafil on Pre-Eclampsia-Like Mouse Model Induced By L-Name.

N(omega)-nitro-L-arginine methyl ester (L-NAME) decreases the vasodilator effect of nitric oxide (NO) and induces pre-eclampsia in mouse. Sildenafil inhibits the degradation of nitric oxide and increases vasodilation. This study aimed to determine the effects of sildenafil citrate on angiogenesis and oxidative stress at the maternal foetal interface on pre-eclampsia-like mouse model induced by L-NAME. Twenty pregnant mice were divided into four groups: (i) vehicle control; (ii) L-NAME; (iii) sildenafil; (4) L-NAME+sildenafil. L-NAME was administered from day 7 of pregnancy and sildenafil from day 8 until day 16; animals were euthanized on day 17. Placental and foetal sizes and weights were measured; lipid peroxide levels and catalase activity in placental homogenates were determined, and placental vascular endothelia were identified by lectin-histochemistry using BSA-I lectin. Western blot analysis was used to determine VEGF expression in placental homogenates. No changes were seen in placental and foetal development in mice with normal pregnancies treated with sildenafil. Treatments with L-NAME reduced significantly the placental weight and average height and decreased the percentage of the endothelial surface. These alterations may be mediated by the reduction of NO levels in trophoblastic cells, due to the inhibitory effect of L-NAME on nitric oxide synthase (NOS) synthesis. This effect was offset by the treatment with sildenafil, with an increase in the percentage of the endothelial surface. In conclusion, our results indicate that treatment with sildenafil on pre-eclampsia mouse model can be used without adverse effects on the concept and its use in the treatment of pre-eclampsia is promising.

Production of microparticles with gelatin and chitosan.

In the past few decades, the textile industry has significantly increased investment in research to develop functional fabrics, with a special focus on those aggregating values. Such fabrics can exploit microparticles inferior to 100 µm, such as those made by complex coacervation in their creation. The antimicrobial properties of chitosan can be attributed to these microparticles. Developing particles with uniform structure and properties would facilitate the control for the eventual release of the core material. Thus, a complex coacervation between gelatin and chitosan was studied, and the optimal conditions were replicated in the encapsulation of limonene. Spherical particles formed had an average diameter (D3,2) of 30 µm and were prepared with 89.7% efficiency. Cross-linking of these microparticles using glutaraldehyde and tripolyphosphate was carried out before spray drying. After drying, microparticles cross-linked with glutaraldehyde were oxidized and clustered and those that were cross-linked with tripolyphosphate resisted drying and presented a high yield.

Gender differences in HIV infection: is there a problem? Analysis from the SCOLTA cohorts.

OBJECTIVES: Evaluate gender differences with regard to baseline characteristics and outcome of therapy in cohorts of the SCOLTA (surveillance cohort long-term toxicity of antiretrovirals) project. METHODS: The SCOLTA project is an active pharmacovigilance system for new antiretroviral drugs. Since 2002, patients were enrolled in nine cohorts (lopinavir, tenofovir, atazanavir, fosamprenavir, enfuvirtide, tipranavir, darunavir, raltegravir and maraviroc). RESULTS: Two thousand one hundred and fifty-four patients were included in 5 PI cohorts; 607 (28.2%) were female. Women were younger and less frequently HCV-coinfected than men. At study entry, they were less frequently in CDC stage C, but CD4+ cells/mm(3) and detectable HIV-RNA were not different by gender. Women had triglycerides alterations less frequently than men, but showed a higher proportion of low HDL-cholesterol. Women were protected from incident grade 2-4 triglycerides increase (odds ratio=0.39, 95% confidence interval 0.18-0.88; P=0.02). Mean CD4+ cell count increased in both men and women; despite a non-significantly lower initial CD4+ level, women had a better immunological recovery. Women discontinued PI treatment for adverse events and their own will more frequently. CONCLUSIONS: In these cohorts, gender distribution mirrored the Italian HIV population. Women were younger than men when they started their first ARV therapy and when they entered our cohorts. On the same treatment, they had a better immune response, though no significant difference emerged on virologic control and treatment durability. As compared to men, women appeared at lower risk of hypertriglyceridaemia. They stopped PI-based treatment of their own will more frequently than men, suggesting the need for a focused effort on adherence.

Microencapsulation of Lactobacillus acidophilus La-5 by spray-drying using sweet whey and skim milk as encapsulating materials.

The aim of this study was to evaluate the effect of encapsulating material on encapsulation yield, resistance to passage through simulated gastrointestinal conditions, and viability of Lactobacillus acidophilus La-5 during storage. Microparticles were produced from reconstituted sweet whey or skim milk (30% total solids) inoculated with a suspension of L. acidophilus La-5 (1% vol/vol) and subjected to spray-drying at inlet and outlet temperatures of 180°C and 85 to 95°C, respectively. The samples were packed, vacuum-sealed, and stored at 4°C and 25°C. Encapsulation yield, moisture content, and resistance of microencapsulated L. acidophilus La-5 compared with free cells (control) during exposure to in vitro gastrointestinal conditions (pH 2.0 and 7.0) were evaluated. Viability was assessed after 0, 7, 15, 30, 45, 60, and 90d of storage. The experiments were repeated 3 times and data were analyzed by ANOVA and Tukey test for the comparison between means. The encapsulating material did not significantly affect encapsulation yield, average diameter, or moisture of the particles, which averaged 76.58±4.72%, 12.94±0.78µm, and 4.53±0.32%, respectively. Both microparticle types were effective in protecting the probiotic during gastrointestinal simulation, and the skim milk microparticles favored an increase in viability of L. acidophilus La-5. Regardless of the encapsulating material and temperature of storage, viability of the microencapsulated L. acidophilus La-5 decreased on average 0.43 log cfu/g at the end of 90d of storage, remaining higher than 10(6)cfu/g.

The use of flavonoids in central nervous system disorders.

Neurodegenerative, neurological and psychiatric diseases are a group of pathologies with huge social and economic impacts. Since brain disorders continue to be pathological conditions for which corrective surgery cannot be widely used, treatments are based on drugs that only alleviate the symptoms. Despite all efforts in finding more efficient therapeutic agents, the requirement for neuroprotective drugs able to cross the blood-brain barrier (BBB) has been a hard challenge to overcome. Flavonoids are known by their antioxidant activities thus preventing oxidative stress, which is believe to be one of the causes of disorders affecting the central nervous system. Moreover, they can also modulate both enzymes and receptors activities, being regarded as multi-target botanical therapeutics or drugs. This review will give emphasis to the benefits of flavonoids found in the diet in the treatment of Alzheimer's disease, Parkinson's disease, epilepsy, depression, and schizophrenia. The antioxidant effect of several flavonoids, as well as their effects not related with antioxidant activity, in the above mentioned diseases will be reviewed. Aspects concerning structure-activity relationships, but also the bioavailability of these compounds in the brain will be referred.

Whey protein coating bead improves the survival of the probiotic Lactobacillus rhamnosus CRL 1505 to low pH.

AIMS: To evaluate the efficacy of a novel microencapsulation procedure using whey protein and pectin to improve the survival rate of Lactobacillus rhamnosus CRL 1505 to low pH and bile. METHODS AND RESULTS: Lactobacillus rhamnosus CRL 1505 was encapsulated by ionotropic gelation using pectin (PE) and pectin-whey protein (PE-WP). Both types of beads (MC(PE/WP) and MC(PE-WP/WP)) were covered with a layer of whey protein by complex coacervation. The noncapsulated lactobacilli were not sensitive to bile salts but to acid. Both microparticles protected Lact. rhamnosus CRL 1505 at pH 2.0, but only MC(PE/WP) was effective at pH 1.2. CONCLUSIONS: The combination of ionotropic gelation and complex coacervation techniques is efficient to obtain microcapsules of pectin covered with whey proteins. The MC(PE/WP) beads were more stable than the MC(PE-WP/WP) beads in simulated gastric conditions, thus offering better protection to Lact. rhamnosus CRL 1505 at low pH. SIGNIFICANCE AND IMPACT OF THE STUDY: Pectin beads with a whey protein layer (MC(PE/WP)) could be used as probiotic carrier in functional foods of low pH (e.g. apple juice), thus protecting Lact. rhamnosus CRL 1505 against the stressful conditions of the gastric tract.

Efficacy and safety of boosted and unboosted atazanavir-containing antiretroviral regimens in real life: results from a multicentre cohort study.

BACKGROUND: Atazanavir (ATV) has demonstrated high efficacy and safety in both treatment-naïve and treatment-experienced patients. Some comparative data are available on the durability of ritonavir-boosted (ATV/r) and unboosted formulations, but there are no data on clinicians' motivations for choosing one or another in everyday practice. The aim of this study was to evaluate the long-term efficacy of boosted and unboosted ATV in a cohort of treatment-experienced patients. METHODS: All patients included in the study were enrolled in an observational cohort within the Surveillance Cohort Long-Term Toxicity Antiretrovirals (SCOLTA) Project. Data on CD4 cell count, HIV viral load, metabolic parameters and adverse events of grade 3-4 are collected through an on-line system every six months. The duration of treatment with ATV was evaluated using the Kaplan-Meier curve and boosted and unboosted regimens were compared using the log-rank test. RESULTS: A total of 509 patients starting ATV as a component of their antiretroviral therapy were enrolled in the SCOLTA Project at the time of the study. Boosted ATV was received by 379 patients (74.5%) while 130 (25.5%) were treated with the unboosted formulation. The last therapeutic regimen did not influence the choice of ATV formulation. The mean observational time was 23.9 months. At the end of follow-up, 58.5% of patients on unboosted ATV and 58.1% of patients on ATV/r continued the treatment and no statistically significant differences were observed for ATV durability between the formulations or among the single causes of therapy interruption. CONCLUSIONS: Our results suggest that, in unselected clinical settings, ATV-containing antiretroviral therapy is durable and safe in both its formulations.

Antioxidant activities of the supercritical and conventional Satureja montana extracts.

The antioxidant activities of the volatile and the nonvolatile fractions from Satureja montana obtained by supercritical fluid extraction (SFE) and by conventional techniques, hydrodistillation (HD) and soxhlet extraction (SE), were compared. A good agreement between DPPH and rancimat methods was obtained showing that the extracts were able to scavenge free radicals and to inhibit lipid oxidation. The volatile oil (obtained by SFE at 90 bar/40 degrees C) was the most effective extract, presenting the lowest EC(50) (0.06 g/L) and the highest protector factor (PF = 2.03). These results demonstrated the advantages of SFE over conventional techniques by avoiding thermodegradation and hydrolysis reactions. Furthermore, volatile oil is 15 times richer in thymoquinone than the essential oil (HD). This compound is of great importance due to its antioxidant, neuroprotective, and anti-cancer activities. The combination of carvacrol + thymol + thymoquinone in volatile oil may be responsible for the increase in the antioxidant activity when compared to HD, which demonstrates that, in this case, SFE improves value to the final product.

Cashew gum microencapsulation protects the aroma of coffee extracts.

Microencapsulation of materials rich in volatile compounds by spray drying presents the challenge of removing water by vapourization without loss of odour and/or flavour components. Crioconcentrated coffee extracts rich in odour components were used as a substrate core to evaluate microencapsulation with cashew gum from Anacardium occidentale L. In Brazil, cashew gum is a low cost alternative to the traditional Arabic gum. A suspension containing coffee extract and the wall material was dissolved in water and then passed through a spray dryer. Core microcapsules were microwave-assisted extracted (MAE) and the aroma protection of the microcapsules produced was evaluated using gas chromatography and mass spectroscopy (GC/MS). The external morphology and size distribution of the microcapsules were obtained by scanning electron microscopy (SEM) and light scattering techniques, respectively. When comparing Arabic and cashew gum microencapsulation of coffee extracts both wall materials were observed to have similar aroma protection, external morphology and size distribution. Sensory analysis was employed to examine flavour protection and consumer preference with microencapsulation. These biochemical, sensory and structural data suggest that low cost cashew gum is a well suited alternative for odour microencapsulation to the more costly Arabic gum currently used in Brazil.

Caspase-3 cleaved spectrin colocalizes with neurofilament-immunoreactive neurons in Alzheimer's disease.

Corticocortical disconnection in Alzheimer's disease occurs by the progressive impairment and eventual loss of a small subset of pyramidal neurons in layers III and V of association areas of the neocortex. These neurons exhibit large somatic size, extensive dendritic arborization and high levels of nonphosphorylated neurofilaments of medium and high molecular weight that can be identified using a monoclonal SMI-32 antibody. It is thought that the accumulation of amyloid Abeta and neurofibrillary tangles may provoke metabolic disturbances that result in the loss of these SMI-32 immunoreactive neurons. The recent detection of increased levels of caspase-3 cleaved fodrin in frontal, temporal and parietal association areas in Alzheimer's disease brains suggests that programmed cell death may contribute to the destruction of SMI-32 positive neurons. In the present study, we utilized an antibody that selectively recognizes the 120 kDa breakdown product of alphaIIspectrin (fodrin) generated by caspase-3 to determine whether this protease is activated in vulnerable pyramidal neurons located in layers III and V of Alzheimer's disease brains. Neurons immunoreactive for caspase-3 cleaved alphaIIspectrin were located predominantly in layers III and V of the inferior frontal and superior temporal cortices of patients with Alzheimer's disease but not age-matched controls. Pyramidal neurons immunoreactive for caspase-3 cleaved alphaIIspectrin invariably displayed SMI-32 immunoreactivity suggesting that caspase-3 activation is a pathological event that may be responsible for the loss of a subset of pyramidal neurons that comprise corticocortical projections.

Maternal mutation 677C > T in the methylenetetrahydrofolate reductase gene associated with severe brain injury in offspring.

A frequent polymorphism in the gene coding for 5,10-methylenetetrahydrofolate reductase is the substitution 677C > T which produces a thermolabile and inefficient enzyme. Homozygosity for the 677C > T allele is the most important determinant of hyperhomocys-teinemia, when folic acid intake is reduced. Most studies on the relationship between the 677C > T variant in the mother and defects in the offspring have focused on neural-tube defects. This study is a retrospective case-control investigation of hypoxic-ischemic encephalopathy of the newborn (HIEN) with reference to the 677C > T polymorphism as a genetic risk for this condition. The prevalence of the 677C > T allele was studied in 11 children with HIEN, their respective mothers, and 85 healthy individuals. Plasma homocysteine levels after fasting and methionine loading were determined in both mothers and controls. Ten of 11 patients were evaluated using magnetic resonance (MR) imaging, and all showed multicystic encephalomalacia and severe brain vasculopathy. Seven mothers were homozygous and four heterozygous for the 677C > T allele. Five of the children were homozygous and six heterozygous for this polymorphism. The variant allele frequency was higher in the group of mothers with affected children than in the controls and was associated with an increase in plasma homocysteine after methionine loading, in the group of mothers than in controls. The 677C > T mutation in mothers, either in a homozygous or heterozygous state, together with poor nutritional status (probable folate deficiency) may represent a risk factor for irreversible HIEN in the offspring.

Effects of fimbria-fornix transection on calpain and choline acetyl transferase activities in the septohippocampal pathway.

The ability of fimbria-fornix bilateral axotomy to elicit calpain and caspase-3 activation in the rat septohippocampal pathway was determined using antibodies that selectively recognize either calpain- or caspase-cleaved products of the cytoskeletal protein alphaII-spectrin. Radioenzymatically determined choline acetyl transferase (ChAT) activity was elevated in the septum at day 5, but reduced in the dorsal hippocampus at days 3, 5 and 7, after axotomy. Prominent accumulation of calpain-, but not caspase-3-, cleaved spectrin proteolytic fragments was observed in both the septum and dorsal hippocampus 1-7 days after axotomy. ChAT-positive neuronal cell bodies in the septum also displayed calpain-cleaved spectrin indicating that calpain activation occurred in cholinergic septal neurons as a consequence of transection of the septohippocampal pathway. Calpain-cleaved alphaII-spectrin immunoreactivity was observed in cholinergic fibers coursing through the fimbria-fornix, but not in pyramidal neurons of the dorsal hippocampus, suggesting that degenerating cholinergic nerve terminals were the source of calpain activity in the dorsal hippocampus following axotomy. Accumulation of calpain-cleaved spectrin proteolytic fragments in the dorsal hippocampus and septum at day 5 after axotomy was reduced by i.c.v. administration of two calpain inhibitors. Calpain inhibition partially reduced the elevation of ChAT activity in the septum produced by transection but failed to decrease the loss of ChAT activity in the dorsal hippocampus following axotomy. These findings suggest that calpain activation contributes to the cholinergic cell body response and hippocampal axonal cytoskeletal degradation produced by transection of the septohippocampal pathway.

Controlled release of protein from hydrocolloid gel microbeads before and after drying.

Casein entrapped within gel microbeads using alginate, amidated LM pectin, gellan gum and a system containing a mixture of these polysaccharides (pectin:gellan:alginate, 1/3: 1/3: 1/3), were obtained by ionic gelation in a high-pressure capillary apparatus. Hydrogenated vegetable fat was also added to produce the gel microbeads and protein release in all the systems was measured, including from freeze-dried capsules containing protein and fat. Encapsulation efficiency, capsule size and morphology were evaluated as well as the protein release profile. Encapsulation efficiencies from 83.7 to 90.7% were obtained for the protein capsules and from 71.8 to 95.4% for those containing protein and fat. Greater release was observed from gel microbeads without fat where alginate presented the greatest diffusion (100%) and the system with a mixture of polyssacharides, the best barrier, with protein retention of 90% after 240 min in solution. The fat containing gel microbeads presented good percent retentions and both the gel microbeads and the dry microbeads showed similar percentages for release. The majority of the systems studied showed a burst effect on release. Gel microbeads size distribution was similar, both with and without fat, and independent of the matrix material, the mean size being 150microm. The morphological observations showed that the gel microbeads were spheroidal with a homogenous distribution of fat droplets in the microcapsules. Agglomeration occurred on drying but many particles maintained a partially spheroidal form, with a configuration of solid material.

Study of the microencapsulation of camu-camu (Myrciaria dubia) juice.

The camu-camu, like many other Amazonian fruits, shows an excellent potential for use due to its high vitamin C content, and the use of these natural resources could result in greater development of the Amazonian region. Few studies have been conducted with this fruit, and such studies are necessary in order to develop the required technology to allow for its utilization, thus avoiding or at least decreasing wastage of such a rich raw material. The principle objective of this study was to develop a process for the microencapsulation of camu-camu juice, optimizing the operational conditions. The processing conditions consisted of blanching at a temperature of 95 +/- 2 degrees C for 2 min, followed by cooling in an ice bath and juice extraction using a brush type depulper. The juice was dried with gum arabic or malt dextrin in a mini-spray dryer using an air entry temperature of between 100-160 degrees C and wall material concentration varying between 5-35%, in accordance with a factorial experimental design. Both the air entry temperature and the amount of wall material, plus the interaction between the two, gave significant positive effects at the level of 5% probability on the yield of juice powder. The optimum conditions for juice yield and vitamin C retention were established as 15% wall material and an air entry temperature of 150 degrees C.

Microencapsulation of L. acidophilus (La-05) and B. lactis (Bb-12) and evaluation of their survival at the pH values of the stomach and in bile.

Microcapsules were prepared using the probiotic microorganisms Lactobacillus acidophilus (La-05) and Bifidobacterium lactis (Bb-12) and the spray drying technique and cellulose acetate phthalate as the wall material. This study evaluated the resistance of these microorganisms to drying at three temperatures and also the in vitro tolerance of the free and microencapsulated form to pH values and bile concentrations similar to those found in the human stomach and intestine. With an air entry temperature of 130 degrees C and exit temperature of 75 degrees C, the number of viable cells of B. lactis was practically unaltered, whereas the population of L. acidophilus was reduced by two logarithmic cycles. B. lactis was more resistant to the drying process than L. acidophilus under all conditions tested. The morphology of the microcapsules was determined by scanning electron microscopy and the microcapsules presented a rounded external surface containing concavities, a continuous wall with no apparent porosity, average size of 22 microm, moisture content varying from 5.3 to 3.2% and water activity between 0.230 and 0.204. After inoculation into HCl solutions with pH values adjusted to 1 and 2, incubated anaerobically at 37 degrees C, and plated after 0, 1 and 2 h of incubation, microcapsules were effective in protecting the microorganisms, while the populations of both free microorganisms were eliminated after only 1 h at the acidic conditions. Microencapsulated B. lactis and L. acidophilus, both free and microencapsulated, were also resistant after 12h to bile solutions.

The validity of clinical examination in adolescent spinal deformities.

STUDY DESIGN: retrospective study on the accuracy and reliability of two clinical tests for scoliosis in young patients. AIM: to evaluate the inter-observer reliability of three non-invasive clinical measurements: hump height (HH), axial trunk rotation (ATR), and distance of the spinous process from the plumb line (DP) in standing; to compare these results with the corresponding radiographic measurements, the Cobb angles (CA). POPULATION: 116 patients, 78 females and 38 males; 410 examinations have been performed (144 patients with brace and 266 without). METHODS: a database was created using the measurements of different clinical parameters obtained from two examiners that measured them independently and in the same conditions. The Cobb method has been used as a gold standard. RESULTS: our results show a very high inter-rater reliability for HH and ATR measurements. The DP shows a different inter-rater reliability for the thoracic (C7) and lumbar (L3) spine, in both cases lower than that in the frontal plane; the ICC of the thoracolumbar DP (D12) was very low. The correlation with the radiographic value was weak.