Photoelectrochemical advanced oxidation processes on nanostructured TiO₂ catalysts: decolorization of a textile azo-dye

This work describes a novel approach for water treatment by photoelectrocatalysis, based on nanostructured TiO₂. The decolorization of aqueous solutions containing the azo-dye RR243 is carried out in a tubular photocatalytic reactor working in semi-batch mode under electrical polarization of the catalyst. Two different nanostructured catalysts were tested: nanotubular TiO₂ obtained by conventional anodization (CA), and a novel photoactive nanoporous TiO₂, obtained by plasma electrolytic oxidation (PEO). Neither UV irradiation of the TiO₂ catalysts nor the electrical bias individually considered lead to a significant reduction of the dye concentration. By irradiating the catalysts with UVC light while applying an electrical bias to the same, the concentration of the dye decreased from 25 L to 2,5 mg/L using the nanotubular CA TiO₂ catalyst, and to less than 1,8 mg/L using the novel nanoporous PEO TiO₂ in 50 min. The main advantages of this method over current approaches for the degradation of pollutants are both the considerable processing time reduction and a suitable and easy-to-scale-up reactor design. A further advantage is the relatively easyness in the production of the TiO₂ catalysts by PEO

Photoelectrochemical advanced oxidation processes on nanostructured TiO₂ catalysts: decolorization of a textile azo-dye

This work describes a novel approach for water treatment by photoelectrocatalysis, based on nanostructured TiO₂. The decolorization of aqueous solutions containing the azo-dye RR243 is carried out in a tubular photocatalytic reactor working in semi-batch mode under electrical polarization of the catalyst. Two different nanostructured catalysts were tested: nanotubular TiO₂ obtained by conventional anodization (CA), and a novel photoactive nanoporous TiO₂, obtained by plasma electrolytic oxidation (PEO). Neither UV irradiation of the TiO₂ catalysts nor the electrical bias individually considered lead to a significant reduction of the dye concentration. By irradiating the catalysts with UVC light while applying an electrical bias to the same, the concentration of the dye decreased from 25 L to 2,5 mg/L using the nanotubular CA TiO₂ catalyst, and to less than 1,8 mg/L using the novel nanoporous PEO TiO₂ in 50 min. The main advantages of this method over current approaches for the degradation of pollutants are both the considerable processing time reduction and a suitable and easy-to-scale-up reactor design. A further advantage is the relatively easyness in the production of the TiO₂ catalysts by PEO

9q34.3 microduplications lead to neurodevelopmental disorders through EHMT1 overexpression

Both copy number losses and gains occur within subtelomeric 9q34 region without common breakpoints. The microdeletions cause Kleefstra syndrome (KS), whose responsible gene is EHMT1. A 9q34 duplication syndrome (9q34 DS) had been reported in literature, but it has never been characterized by a detailed molecular analysis of the gene content and endpoints. To the best of our knowledge, we report on the first patient carrying the smallest 9q34.3 duplication containing EHMT1 as the only relevant gene. We compared him with 21 reported patients described here as carrying 9q34.3 duplications encompassing the entire gene and extending within ~\u20093 Mb. By surveying the available clinical and molecular cytogenetic data, we were able to discover that similar neurodevelopmental disorders (NDDs) were shared by patient carriers of even very differently sized duplications. Moreover, some facial features of the 9q34 DS were more represented than those of KS. However, an accurate in silico analysis of the genes mapped in all the duplications allowed us to support EHMT1 as being sufficient to cause a NDD phenotype. Wider patient cohorts are needed to ascertain whether the rearrangements have full causative role or simply confer the susceptibility to NDDs and possibly to identify the cognitive and behavioral profile associated with the increased dosage of EHMT1

Targeted whole exome sequencing and Drosophila modelling to unveil the molecular basis of primary ovarian insufficiency

STUDY QUESTION: Can a targeted whole exome sequencing (WES) on a cohort of women showing a primary ovarian insufficiency (POI) phenotype at a young age, combined with a study of copy number variations, identify variants in candidate genes confirming their deleterious effect on ovarian function? SUMMARY ANSWER: This integrated approach has proved effective in identifying novel candidate genes unveiling mechanisms involved in POI pathogenesis. WHAT IS KNOWN ALREADY: POI, a condition occurring in 1% of women under 40 years of age, affects women’s fertility leading to a premature loss of ovarian reserve. The genetic causes of POI are highly heterogeneous and several determinants contributing to its prominent oligogenic inheritance pattern still need to be elucidated. STUDY DESIGN, SIZE, DURATION: WES screening for pathogenic variants of 41 Italian women with non-syndromic primary and early secondary amenorrhoea occurring before age 25 was replicated on another 60 POI patients, including 35 French and 25 American women, to reveal statistically significant shared variants. PARTICIPANTS/MATERIALS, SETTING, METHODS: The Italian POI patients’ DNA were processed by targeted WES including 542 RefSeq genes expressed or functioning during distinct reproductive or ovarian processes (e.g. DNA repair, meiosis, oocyte maturation, folliculogenesis and menopause). Extremely rare variants were filtered and selected by means of a Fisher Exact test using several publicly available datasets. A case-control Burden test was applied to highlight the most significant genes using two ad-hoc control female cohorts. To support the obtained data, the identified genes were screened on a novel cohort of 60 Caucasian POI patients and the same case-control analysis was carried out. Comparative analysis of the human identified genes was performed on mouse and Drosophila melanogaster by analysing the orthologous genes in their ovarian phenotype, and two of the selected genes were fruit fly modelled to explore their role in fertility. MAIN RESULTS AND THE ROLE OF CHANCE: The filtering steps applied to search for extremely rare pathogenic variants in the Italian cohort revealed 64 validated single-nucleotide variants/Indels in 59 genes in 30 out of 41 screened women. Burden test analysis highlighted 13 ovarian genes as being the most enriched and significant. To validate these findings, filtering steps and Burden analysis on the second cohort of Caucasian patients yielded 11 significantly enriched genes. Among them, AFP, DMRT3, MOV10, FYN and MYC were significant in both patient cohorts and hence were considered strong candidates for POI. Mouse and Drosophila comparative analysis evaluated a conserved role through the evolution of several candidates, and functional studies using a Drosophila model, when applicable, supported the conserved role of the MOV10 armitage and DMRT3 dmrt93B orthologues in female fertility. LARGE SCALE DATA: The datasets for the Italian cohort generated during the current study are publicly available at ClinVar database (http://www.ncbi.nlm.nih.gov/clinvar/): accession numbers SCV001364312 to SCV001364375. LIMITATIONS, REASONS FOR CAUTION: This is a targeted WES analysis hunting variants in candidate genes previously identified by different genomic approaches. For most of the investigated sporadic cases, we could not track the parental inheritance, due to unavailability of the parents’ DNA samples; in addition, we might have overlooked additional rare variants in novel candidate POI genes extracted from the exome data. On the contrary, we might have considered some inherited variants whose clinical significance is uncertain and might not be causative for the patients’ phenotype. Additionally, as regards the Drosophila model, it will be extremely important in the future to have more mutants or RNAi strains available for each candidate gene in order to validate their role in POI pathogenesis. WIDER IMPLICATIONS OF THE FINDINGS: The genomic, statistical, comparative and functional approaches integrated in our study convincingly support the extremely heterogeneous oligogenic nature of POI, and confirm the maintenance across the evolution of some key genes safeguarding fertility and successful reproduction. Two principal classes of genes were identified: (i) genes primarily involved in meiosis, namely in synaptonemal complex formation, asymmetric division and oocyte maturation and (ii) genes safeguarding cell maintenance (piRNA and DNA repair pathways). STUDY FUNDING/COMPETING INTEREST(S): This work was supported by Italian Ministry of Health grants ‘Ricerca Corrente’ (08C621_2016 and 08C924_2019) provided to IRCCS Istituto Auxologico Italiano, and by ‘Piano Sostegno alla Ricerca’ (PSR2020_FINELLI_LINEA_B) provided by the University of Milan; M.P.B. was supported by Telethon-Italy (grant number GG14181). There are no conflicts of interest

Targeted whole exome sequencing and Drosophila modelling to unveil the molecular basis of primary ovarian insufficiency

STUDY QUESTION: Can a targeted whole exome sequencing (WES) on a cohort of women showing a primary ovarian insufficiency (POI) phenotype at a young age, combined with a study of copy number variations, identify variants in candidate genes confirming their deleterious effect on ovarian function? SUMMARY ANSWER: This integrated approach has proved effective in identifying novel candidate genes unveiling mechanisms involved in POI pathogenesis. WHAT IS KNOWN ALREADY: POI, a condition occurring in 1% of women under 40 years of age, affects women’s fertility leading to a premature loss of ovarian reserve. The genetic causes of POI are highly heterogeneous and several determinants contributing to its promi-nent oligogenic inheritance pattern still need to be elucidated. STUDY DESIGN, SIZE, DURATION: WES screening for pathogenic variants of 41 Italian women with non-syndromic primary and early secondary amenorrhoea occurring before age 25 was replicated on another 60 POI patients, including 35 French and 25 American women, to reveal statistically significant shared variants. PARTICIPANTS/MATERIALS, SETTING, METHODS: The Italian POI patients’ DNA were processed by targeted WES including 542 RefSeq genes expressed or functioning during distinct reproductive or ovarian processes (e.g. DNA repair, meiosis, oocyte maturation, folliculogenesis and menopause). Extremely rare variants were filtered and selected by means of a Fisher Exact test using several publicly available datasets. A case-control Burden test was applied to highlight the most significant genes using two ad-hoc control female cohorts. To support the obtained data, the identified genes were screened on a novel cohort of 60 Caucasian POI patients and the same case-control analysis was carried out. Comparative analysis of the human identified genes was performed on mouse and Drosophila melanogaster by analysing the orthologous genes in their ovarian phenotype, and two of the selected genes were fruit fly modelled to explore their role in fertility.MAIN RESULTS AND THE ROLE OF CHANCE: The filtering steps applied to search for extremely rare pathogenic variants in the Italian cohort revealed 64 validated single-nucleotide variants/Indels in 59 genes in 30 out of 41 screened women. Burden test analysis highlighted 13 ovarian genes as being the most enriched and significant. To validate these findings, filtering steps and Burden analysis on the second cohort of Caucasian patients yielded 11 significantly enriched genes. Among them, AFP, DMRT3, MOV10, FYN and MYC were significant in both patient cohorts and hence were considered strong candidates for POI. Mouse and Drosophila comparative analysis evaluated a conserved role through the evolution of several candidates, and functional studies using a Drosophila model, when applicable, supported the conserved role of the MOV10 armitage and DMRT3 dmrt93B orthologues in female fertility

Exploring the Emotional Breastfeeding Experience of First-Time Mothers : Implications for Healthcare Support

Background: Among breastfeeding determinants, the unique emotional breastfeeding experience has been poorly explored. The present study aimed to investigate the emotional breastfeeding experience in a cohort of first-time mothers. Materials and methods: We conducted a prospective observational study that enrolled primiparas having delivered singleton healthy term newborns, and exclusively breastfeeding at hospital discharge. At 3 months post-delivery mothers accessed an online questionnaire investigating their emotional breastfeeding experience. The chi-squared test was used to assess the association between the feelings experienced during breastfeeding and feeding outcomes at 3 months. Results: Out of the 421 enrolled mothers, 273 (65%) completed the questionnaire. At 3 months post-delivery exclusive breastfeeding was reported by a 66% of mothers, a 19% reported complementary feeding, and a 15% of mothers reported exclusive formula feeding. Breastfeeding experience was described as positive by 62% of mothers although breastfeeding difficulties were reported by 80% of the mothers. The mothers that had experienced fear, sadness, anger or concern during breastfeeding showed a significant higher exclusive formula feeding rate at 3 months post-delivery than those who did not (25.5 vs. 12.8%, p = 0.021; 28.6 vs. 13.4%, p = 0.02; 40 vs. 13.4%, p = 0.005; 20.5 vs. 11.8%, p = 0.049, respectively). An 85% of mothers stated that their breastfeeding experience was different from what they would have expected, blaming for this discrepancy the occurrence of difficulties during breastfeeding and the complexity of breastfeeding itself (50%), pain experience (8%), being dependent from the baby (6%), and breastfeeding failure (11%). A total of 25% of mothers, however, reported they found breastfeeding to be a much more positive experience than what they had expected. Conclusion: Breastfeeding care should include a tailored emotional support of first time-mothers in addition to the implementation of their breastfeeding knowledge and skills

Chagas disease knocks on our door : A cross-sectional study among Latin American immigrants in Milan, Italy

Objectives: We aimed to assess the prevalence and risk factors for Chagas disease (CD) in Latin American immigrants and to evaluate the accuracy of diagnostic tests. Moreover, we offered to all positive subjects a complete free-of-charge clinical/instrumental evaluation as well as benznidazole treatment in order to stage the disease and verify drug tolerability. Methods: A cross-sectional survey of CD among Latin Americans living in Milan and its metropolitan area was conducted between July 2013 and July 2014. Blood samples were tested for serologic evidence of CD together with a questionnaire covering demographic and clinical-epidemiological information. Results: Forty-eight (9.6%) of the 501 tested subjects were conclusively diagnosed as having CD. The highest prevalence of CD was among those from Bolivia (43/169, 25.4%) and El Salvador (4/68, 5.9%). Older age (adjusted odds ratio (aOR)] 1.05, p =0.004), a Bolivian origin (aOR 8.80; p =0.003), being born in the department of Santa Cruz (aOR 3.72, p =0.047), having lived in mud houses (aOR 2.68; p =0.019), and having an affected relative (aOR 12.77, p =0.001) were independently associated with CD. The ARCHITECT Chagas test showed the highest sensitivity (100%) and specificity (99.8%). Twenty-nine of the subjects with CD (60.4%) underwent disease staging, 10 of whom (35.7%) showed cardiac and/or digestive involvement. Benznidazole treatment was associated with high frequency of adverse reactions (19/27, 70.4%) and permanent discontinuation (8/27, 29.6%). Conclusions: CD is highly prevalent among Bolivians and Salvadorans living in Milan. Regions with a large Latin American immigrant population should implement programmes of active detection and treatment

Familial intragenic duplication of ANKRD11 underlying three patients of KBG syndrome

Background: KBG syndrome, a rare autosomal disorder characterised by distinctive craniofacial and skeletal features and developmental delay, is caused by haploinsufficiency of the ANKRD11 gene. Results: Here we describe two siblings with multiple symptoms characteristic of KBG and their mother with a milder phenotype. In the siblings, array-based comparative genomic hybridization (array CGH) identified an intragenic microduplication affecting ANKRD11 that was absent from the parents' array CGH profiles. Microsatellite analysis revealed the maternal origin of the rearrangement and interphase fluorescent in situ hybridization (i-FISH) experiments identified the rearrangement in low-level mosaicism in the mother. Molecular characterisation of the duplication allele demonstrated the presence of two mutant ANKRD11 transcripts containing a premature stop codon and predicting a truncated non-functional protein. Conclusions: Similarly to deletions and point mutations, this novel pathogenetic rearrangement causes haploinsufficiency of ANKRD11, resulting in KBG syndrome

Evaluation of different counting methods for use in radiochemical purity testing procedures for (99m)Tc-labelled radiopharmaceuticals

The efficiency and accuracy of different methods for quality control of radiopharmaceutical preparations for diagnostic purpose were studied. The radiochemical purity of 99mTc Tetrafosmin, 99mTc Exametazime, 99mTc Sestamibi and 99mTc Oxidronate was evaluated by different thin layer chromatography systems, followed by cutting of the strips into two or three sections and by the measurement of radioactivity distribution by dose calibrator or gamma counter. In addition, to confirm the accuracy of these routine procedures, the strips were cut into a number of micro-sections (14–25) and each of them evaluated by the gamma counter. The three tested procedures gave similar results and revealed a good and comparable accuracy. The radioactivity measurement with the dose calibrator remains the most practicable because of the rapidity of execution

Preliminary evidences of safety and efficacy of flavonoids- and omega 3-based compound for muscular dystrophies treatment: a randomized double-blind placebo controlled pilot clinical trial.

Background: Nutritional compounds can exert both anti-inflammatory and anti-oxidant effects. Since these events exacerbate the pathophysiology of muscular dystrophies, we investigated nutraceutical supplementation as an adjuvant therapy in dystrophic patients, to low costs and easy route of administration. Moreover, this treatment could represent an alternative therapeutic strategy for dystrophic patients who do not respond to corticosteroid treatment. Objective: A 24 weeks randomized double-blind placebo-controlled clinical study was aimed at evaluating the safety and efficacy of daily oral administration of flavonoidsand omega3-based natural supplement (FLAVOMEGA) in patients affected by muscular dystrophy with recognized muscle inflammation. Design: We screened 60 patients diagnosed for Duchenne (DMD), Facioscapulohumeral (FSHD), and Limb Girdle Muscular Dystrophy (LGMD). Using a computer-generated random allocation sequence, we stratified patients in a 2:1:1 ratio (DMD:FSHD:LGMD) to one of two treatment groups: continuous FLAVOMEGA, continuous placebo. Of 29 patients included, only 24 completed the study: 15 were given FLAVOMEGA, 14 placebo. Results: FLAVOMEGA was well tolerated with no reported adverse events. Significant treatment differences in the change from baseline in 6 min walk distance (6MWD; secondary efficacy endpoint) (P = 0.033) and in isokinetic knee extension (P = 0.039) (primary efficacy endpoint) were observed in LGMD and FSHD subjects. Serum CK levels (secondary efficacy endpoint) decreased in all FLAVOMEGA treated groups with significant difference in DMD subjects (P = 0.039). Conclusions: Although the small number of patients and the wide range of disease severity among patients reduced statistical significance, we obtained an optimal profile of safety and tolerability for the compound, showing valuable data of efficacy in primary and secondary endpoints