Cataract and optic disk drusen in a patient with glycogenosis and di George syndrome: clinical and molecular report

Background We report the ophthalmic findings of a patient with type Ia glycogen storage disease (GSD Ia), DiGeorge syndrome (DGS), cataract and optic nerve head drusen (ONHD). Case presentation A 26-year-old white woman, born at term by natural delivery presented with a post-natal diagnosis of GSD Ia. Genetic testing by array-comparative genomic hybridization (CGH) for DGS was required because of her low levels of serum calcium. The patient has been followed from birth, attending the day-hospital every six months at the San Paolo Hospital, Milan, outpatient clinic for metabolic diseases and previously at another eye center. During the last day-hospital visit, a complete eye examination showed ONHD and cataract in both eyes. Next Generation Sequencing (NGS) was subsequently done to check for any association between the eye problems and metabolic aspects. Conclusions This is the first description of ocular changes in a patient with GSD Ia and DGS. Mutations explaining GSD Ia and DGS were found but no specific causative mutation for cataract and ONHD. The metabolic etiology of her lens changes is known, whereas the pathogenesis of ONHD is not clear. Although the presence of cataract and ONHD could be a coincidence; the case reported could suggest that hypocalcemia due to DGS could be the common biochemical pathway

More Than Simply “Letting Go”: Stakeholder Perspectives on Parental Roles in Health Care Transition

The transfer from pediatric to adult health care for youth with special health care needs (YSHCN) is a vulnerable period. Parents play a pivotal role in the transition process, however, little is known about the specific ways they may support YSHCN in negotiating the transition to adult services. A qualitative supplementary secondary data analysis was conducted to explore stakeholders’ perceptions about parents’ roles in health care transition. Thematic analysis was used to analyze individual and focus group interviews. Four themes were identified: 1) Parents are crucial; 2) Changing roles; 3) Interdependence rather than independence; 4) One of many transitions. These themes may serve as the basis for planning future intervention studies directed at parents of YSHCN

Energy expenditure in female workers in a textile factory

Autori su ispitivali energetske rashode radnica na tri radna mjesta, i to: šivanje električnim strojem, krojenje električnom pilom i rad na tkalačkom stroju za izradu vrpce. Ispitivanja su vršena standardnim metodama, određivanjem energetskih ekvivalenata za pojedine specifične radnje, izradom vremenskih tablica i preračunavanjem utrošenih kalorija po pojedinim radnim satima. Utrošeno radno vrijeme podijeljeno je na djelatnosti A, B i C. A = rad, osnovni za radno mjesto, B = priprema za izvršavanje osnovnog rada i C = odmor spontani i službeni. Energetska rashodi radnica u tekstilnoj industriji pokazuju velike razlike (do 500 kal.) po pojedinim radnim mjestima. Taj podatak omogućava da se i u ovakvim pogonima lake industrije izvrši diferencijacija radnih mjesta po njihovoj energetskoj opterećenosti. Osim toga ističu potrebu da se ispita mogućnost poboljšanja samog rada, kako bi se uz manji energetski utrošak mogao postići isti radni efekt.The authors have studied the problem of energy expenditure in female workers in a textile factory, by using standard methods. Data evaluated so far show that there is a great difference in energy expenditure for different works in this factory. lt is possible to differentiate the heaviness of work done in this industry, and it is necessary to investigate what should be done to reduce the energy expenditure to a lower level

Energy expenditure in textile workers

Određivani su energetski ekvivalenti za pojedine aktivnosti u tekstilnoj industriji. Ispitivanje je izvršeno kod 17 radnika i radnika poduzeća »Nada Dimić« u Zagrebu. Ukupno je ispitano 80 uzoraka izdahnutog zraka za devet aktivnosti specifičnih za takvo poduzeće. Analiza izdahnutog zraka vršena je metodom po Scholanderu. Dobiveni energetski ekvivalenti pokazuju da je raspon kalorija koje se troše za pojedine radnje dosta velik, pa da u prosjeku varira od 1,56 do 5,63 kal/min, ali se većina radova nalazi na donjoj granici rashoda.The examination of energy expenditure requirement was carried out in a textile factory in Zagreb. 17 workers, women and men, were examined by a Franz-Müller respirometer. Expired air samples were taken and analysed after Scholander. The results shown in calories per minute include values for basal metabolism. The energy expenditure was high only in few cases; in all others the values were very low, corresponding to the values obtained by other authors

Nutraceutical Profiles of Two Hydroponically Grown Sweet Basil Cultivars as Affected by the Composition of the Nutrient Solution and the Inoculation With Azospirillum brasilense

Sweet basil (Ocimum basilicum L.) is one of the most produced aromatic herbs in the world, exploiting hydroponic systems. It has been widely assessed that macronutrients, like nitrogen (N) and sulfur (S), can strongly affect the organoleptic qualities of agricultural products, thus influencing their nutraceutical value. In addition, plant-growth-promoting rhizobacteria (PGPR) have been shown to affect plant growth and quality. Azospirillum brasilense is a PGPR able to colonize the root system of different crops, promoting their growth and development and influencing the acquisition of mineral nutrients. On the bases of these observations, we aimed at investigating the impact of both mineral nutrients supply and rhizobacteria inoculation on the nutraceutical value on two different sweet basil varieties, i.e., Genovese and Red Rubin. To these objectives, basil plants have been grown in hydroponics, with nutrient solutions fortified for the concentration of either S or N, supplied as SO42\u2013 or NO3\u2013, respectively. In addition, plants were either non-inoculated or inoculated with A. brasilense. At harvest, basil plants were assessed for the yield and the nutraceutical properties of the edible parts. The cultivation of basil plants in the fortified nutrient solutions showed a general increasing trend in the accumulation of the fresh biomass, albeit the inoculation with A. brasilense did not further promote the growth. The metabolomic analyses disclosed a strong effect of treatments on the differential accumulation of metabolites in basil leaves, producing the modulation of more than 400 compounds belonging to the secondary metabolism, as phenylpropanoids, isoprenoids, alkaloids, several flavonoids, and terpenoids. The primary metabolism that resulted was also influenced by the treatments showing changes in the fatty acid, carbohydrates, and amino acids metabolism. The amino acid analysis revealed that the treatments induced an increase in arginine (Arg) content in the leaves, which has been shown to have beneficial effects on human health. In conclusion, between the two cultivars studied, Red Rubin displayed the most positive effect in terms of nutritional value, which was further enhanced following A. brasilense inoculation

Inherited variants in CHD3 show variable expressivity in Snijders Blok-Campeau syndrome

Purpose Common diagnostic next-generation sequencing strategies are not optimized to identify inherited variants in genes associated with dominant neurodevelopmental disorders as causal when the transmitting parent is clinically unaffected, leaving a significant number of cases with neurodevelopmental disorders undiagnosed. Methods We characterized 21 families with inherited heterozygous missense or protein-truncating variants in CHD3, a gene in which de novo variants cause Snijders Blok-Campeau syndrome. Results Computational facial and Human Phenotype Ontology–based comparisons showed that the phenotype of probands with inherited CHD3 variants overlaps with the phenotype previously associated with de novo CHD3 variants, whereas heterozygote parents are mildly or not affected, suggesting variable expressivity. In addition, similarly reduced expression levels of CHD3 protein in cells of an affected proband and of healthy family members with a CHD3 protein-truncating variant suggested that compensation of expression from the wild-type allele is unlikely to be an underlying mechanism. Notably, most inherited CHD3 variants were maternally transmitted. Conclusion Our results point to a significant role of inherited variation in Snijders Blok-Campeau syndrome, a finding that is critical for correct variant interpretation and genetic counseling and warrants further investigation toward understanding the broader contributions of such variation to the landscape of human disease

Evolution and Taxonomic Classification of Human Papillomavirus 16 (HPV16)-Related Variant Genomes: HPV31, HPV33, HPV35, HPV52, HPV58 and HPV67

Human papillomavirus 16 (HPV16) species group (alpha-9) of the Alphapapillomavirus genus contains HPV16, HPV31, HPV33, HPV35, HPV52, HPV58 and HPV67. These HPVs account for 75% of invasive cervical cancers worldwide. Viral variants of these HPVs differ in evolutionary history and pathogenicity. Moreover, a comprehensive nomenclature system for HPV variants is lacking, limiting comparisons between studies.DNA from cervical samples previously characterized for HPV type were obtained from multiple geographic regions to screen for novel variants. The complete 8 kb genomes of 120 variants representing the major and minor lineages of the HPV16-related alpha-9 HPV types were sequenced to capture maximum viral heterogeneity. Viral evolution was characterized by constructing phylogenic trees based on complete genomes using multiple algorithms. Maximal and viral region specific divergence was calculated by global and pairwise alignments. Variant lineages were classified and named using an alphanumeric system; the prototype genome was assigned to the A lineage for all types.The range of genome-genome sequence heterogeneity varied from 0.6% for HPV35 to 2.2% for HPV52 and included 1.4% for HPV31, 1.1% for HPV33, 1.7% for HPV58 and 1.1% for HPV67. Nucleotide differences of approximately 1.0% - 10.0% and 0.5%-1.0% of the complete genomes were used to define variant lineages and sublineages, respectively. Each gene/region differs in sequence diversity, from most variable to least variable: noncoding region 1 (NCR1) /noncoding region 2 (NCR2) >upstream regulatory region (URR)> E6/E7 > E2/L2 > E1/L1.These data define maximum viral genomic heterogeneity of HPV16-related alpha-9 HPV variants. The proposed nomenclature system facilitates the comparison of variants across epidemiological studies. Sequence diversity and phylogenies of this clinically important group of HPVs provides the basis for further studies of discrete viral evolution, epidemiology, pathogenesis and preventative/therapeutic interventions

Inherited variants in CHD3 show variable expressivity in Snijders Blok-Campeau syndrome

Purpose: Common diagnostic next-generation sequencing strategies are not optimized to identify inherited variants in genes associated with dominant neurodevelopmental disorders as causal when the transmitting parent is clinically unaffected, leaving a significant number of cases with neurodevelopmental disorders undiagnosed. Methods: We characterized 21 families with inherited heterozygous missense or protein-truncating variants in CHD3, a gene in which de novo variants cause Snijders Blok-Campeau syndrome. Results: Computational facial and Human Phenotype Ontology–based comparisons showed that the phenotype of probands with inherited CHD3 variants overlaps with the phenotype previously associated with de novo CHD3 variants, whereas heterozygote parents are mildly or not affected, suggesting variable expressivity. In addition, similarly reduced expression levels of CHD3 protein in cells of an affected proband and of healthy family members with a CHD3 protein-truncating variant suggested that compensation of expression from the wild-type allele is unlikely to be an underlying mechanism. Notably, most inherited CHD3 variants were maternally transmitted. Conclusion: Our results point to a significant role of inherited variation in Snijders Blok-Campeau syndrome, a finding that is critical for correct variant interpretation and genetic counseling and warrants further investigation toward understanding the broader contributions of such variation to the landscape of human disease

The Role of Osteopontin (OPN/SPP1) Haplotypes in the Susceptibility to Crohn's Disease

Osteopontin represents a multifunctional molecule playing a pivotal role in chronic inflammatory and autoimmune diseases. Its expression is increased in inflammatory bowel disease (IBD). The aim of our study was to analyze the association of osteopontin (OPN/SPP1) gene variants in a large cohort of IBD patients. Genomic DNA from 2819 Caucasian individuals (n = 841 patients with Crohn's disease (CD), n = 473 patients with ulcerative colitis (UC), and n = 1505 healthy unrelated controls) was analyzed for nine OPN SNPs (rs2728127, rs2853744, rs11730582, rs11739060, rs28357094, rs4754 = p.Asp80Asp, rs1126616 = p.Ala236Ala, rs1126772 and rs9138). Considering the important role of osteopontin in Th17-mediated diseases, we performed analysis for epistasis with IBD-associated IL23R variants and analyzed serum levels of the Th17 cytokine IL-22. For four OPN SNPs (rs4754, rs1126616, rs1126772 and rs9138), we observed significantly different distributions between male and female CD patients. rs4754 was protective in male CD patients (p = 0.0004, OR = 0.69). None of the other investigated OPN SNPs was associated with CD or UC susceptibility. However, several OPN haplotypes showed significant associations with CD susceptibility. The strongest association was found for a haplotype consisting of the 8 OPN SNPs rs2728127-rs2853744-rs11730582-rs11439060-rs28357094-rs112661-rs1126772-rs9138 (omnibus p-value = 2.07×10⁻⁸). Overall, the mean IL-22 secretion in the combined group of OPN minor allele carriers with CD was significantly lower than that of CD patients with OPN wildtype alleles (p = 3.66×10⁻⁵). There was evidence for weak epistasis between the OPN SNP rs28357094 with the IL23R SNP rs10489629 (p = 4.18×10⁻²) and between OPN SNP rs1126616 and IL23R SNP rs2201841 (p = 4.18×10⁻²) but none of these associations remained significant after Bonferroni correction. Our study identified OPN haplotypes as modifiers of CD susceptibility, while the combined effects of certain OPN variants may modulate IL-22 secretion

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups