Pericentrin expression in Down’s syndrome

Down’s syndrome (DS) is the most frequent genetic cause of intellectual disability and is a chromosomal abnormality of chromosome 21 trisomy. The pericentrin gene (PCNT) has sequenced in 21q22.3 inside of the minimal critical region for Down’s syndrome. Alterations of PCNT gene are associated with dwarfism, cardiomyopathy and other pathologies. In this study, we have evaluated the possible differential expression of PCNT mRNA, by qRT-PCR, in peripheral blood leukocytes of DS subjects compared with the normal population. In the present case–control study, PCNT gene expression was increased by 72.72 % in 16 out 22 DS samples compared with normal subjects. Our data suggest that changes in the expression levels of PCNT in DS subjects may be involved into the molecular mechanism of Down’s syndrome.     

A randomized clinical trial to evaluate and compare implants placed in augmented versus non-augmented extraction sockets: 3-year results

Background: The alveolar ridge undergoes reabsorption and atrophy subsequent to tooth removal and thus exhibits a wide range of dimensional changes. Preservation of the alveolar crest after tooth extraction is essential to enhance the surgical site before implant fixture placement. The aim of this randomized clinical study is to investigate and compare the need for additional augmentation procedures at implant insertion, as well as the success rate and marginal bone loss for implants placed in the grafted sites versus those placed in naturally healed sites. Methods: Forty patients with ≥1 hopeless tooth were randomly allocated to: 1) a test group, receiving extraction and grafting corticocancellous porcine bone; and 2) a control group, receiving extraction without any graft. After 7 months of healing, implants were inserted in each of the sites. The implants were submerged and loaded after 4 months with metal–ceramic rehabilitation. The follow‐up included evaluation of implant diameter and length, the need for additional augmentation procedures at implant placement, implant failure, and marginal bone level changes. All patients were followed over a 3‐year period. Results: One implant failed in the control group at the second stage of surgery (6 months after placement); one implant failed in the test group after 2 years of loading. The cumulative implant success rate at the 3‐year follow‐up visit reached 95% for both groups. No statistically significant differences were detected for marginal bone changes between the two groups. Conclusions: It was concluded that implants placed into grafted extraction sockets exhibited a clinical performance similar to implants placed into non‐grafted sites in terms of implant survival and marginal bone loss. However, grafted sites allowed placement of larger implants and required less augmentation procedures at implant placement when compared to naturally healed sites.     

A 10-year evaluation of implants placed in fresh extraction sockets: a prospective cohort study

Background: The placement of an implant into a fresh extraction socket has been identified as a reliable technique, allowing a reduction in the time needed for prosthetic rehabilitation. This treatment modality is widely reported in the scientific literature; however, the long-term outcomes and the need for guided bone regeneration (GBR) are still topics of debate. The aim of this prospective study is to evaluate the clinical and radiologic findings from the 10-year follow-up of immediately placed implants, with and without the GBR procedure. Methods: A total of 159 implants in 91 patients are included in this study; 101 implants required a GBR procedure simultaneously with placement. All implants were used to support a single crown restoration. The clinical/radiographic measurements were repeated each year up to the 10-year follow-up. At the 10-year follow-up visit, the papilla index and the apico-coronal location of mid-buccal soft tissue positions were recorded. Results: The 10-year cumulative success rate was 91.8% (87.9% in the non-GBR group and 94.1% in the GBR group). The clinical attachment level (CAL) measurements were stable throughout the study, and 82% of the implants showed marginal bone loss (MBL) of 0.6 to 1.5 mm at the 10-year visit; moreover, these two parameters did not show significant differences between the GBR and non-GBR groups. Seventy percent of the implant sites showed acceptable outcomes in terms of interproximal papilla. The facial gingival level was more apical in the non-GBR group than in the GBR group (P <0.05). Conclusions: The present prospective clinical study shows that implants placed in fresh extraction sockets had a high cumulative success rate, namely 91.8% after 10 years. No differences were detected in survival and success rate of implants whether GBR procedures were performed or not. The CAL, MBL, and marginal level of soft tissue measurements were stable throughout the 10-year evaluation.     

Tyrosinemia Type 1 and symptoms of ADHD: Biochemical mechanisms and implications for treatment and prognosis

Hereditary tyrosinemia Type 1 (HT‐1) is a rare metabolic disease where the enzyme catalyzing the final step of tyrosine breakdown is defect, leading to accumulation of toxic metabolites. Nitisinone inhibits the degradation of tyrosine and thereby the production of harmful metabolites, however, the concentration of tyrosine also increases. We investigated the relationship between plasma tyrosine concentrations and cognitive functions and how tyrosine levels affected enzyme activities of human tyrosine hydroxylase (TH) and tryptophan hydroxylase 2 (TPH2). Eight Norwegian children between 6 and 18 years with HT‐1 were assessed using questionnaires measuring Attention Deficit Hyperactivity Disorder (ADHD)‐symptoms and executive functioning. Recent and past levels of tyrosine were measured and the enzyme activities of TH and TPH2 were studied at conditions replicating normal and pathological tyrosine concentrations. We observed a significant positive correlation between mean tyrosine levels and inattention symptoms. While TH exhibited prominent substrate inhibition kinetics, TPH2 activity also decreased at elevated tyrosine levels. Inhibition of both enzymes may impair syntheses of dopamine, noradrenaline, and serotonin in brain tissue. Inattention in treated HT‐1 patients may be related to decreased production of these monoamines. Our results support recommendations of strict guidelines on plasma tyrosine levels in HT‐1. ADHD‐related deficits, particularly inattention, should be monitored in HT‐1 patients to determine whether intervention is necessary.     

Expanding the clinical and molecular spectrum of lethal congenital contracture syndrome 8 associated with biallelic variants of ADCY6

Arthrogryposis multiplex congenita (AMC) is defined as congenital, non-progressive contractures in more than two joints and in multiple body areas, resulting from reduced fetal mobility. So far, more than 400 causative genes for AMC have been identified. Some isolated AMC phenotypes arise as a result of mutations in genes encoding components required for motor neuron structure, function, and myelination, as in the case of ADCY6 encoding the enzyme adenylyl cyclase type 6. ADCY6 inactivation, due to biallelic variants, have been previously associated with the lethal congenital contracture syndrome 8 (LCCS8). So far, only four LCCS8 patients, from two families, have been reported. Here, we describe a new patient affected by a severe form of AMC, harboring two novel compound heterozygous variants in ADCY6. Our findings expand the clinical and mutational spectrum of LCCS8, showing a possible correlation between the impact of the ADCY6 missense variants reported to date, predicted by molecular modeling, and the severity of the phenotype.