Gardner syndrome: presurgical planning and surgical management of craniomaxillofacial osteomas

Gardner syndrome, a variant of familial adenomatous polyposis, is an autosomal dominant genetic disease characterized by the combined presence of multiple intestinal polyps and extraintestinal manifestations. The extraintestinal manifestations include multiple osteomas, connective tissue tumors, thyroid carcinomas, and hypertrophy of the pigmented epithelium of the retina. Osteoma is a benign neoplasm of bone tissue characterized by slow continuous growth that usually affects the long bones and cranial bones and is a major symptom for Gardner syndrome. The authors report the extraintestinal lesions affecting the maxillofacial regions in 2 male patients (father and son) with Gardner syndrome. The presurgical planning and surgical management of these lesions are described.     

Activin a plasma levels at birth: an index of fetal hypoxia in preterm newborn

Activin-A is a growth factor involved in cell growth and differentiation, neuronal survival, early embryonic development and erythropoiesis. Hypoxemia is a specific trigger for increasing activin-A in fetal lamb circulation. We tested the hypothesis that fetal hypoxia induces activin-A secretion in preterm newborn infants. Fifty newborn infants with gestational ages ranging from 26 to 36 wk were enrolled in a prospective study performed at the Pediatrics, Obstetrics and Reproductive Medicine Department, University of Siena, Italy. Heparinized blood samples were obtained from the umbilical vein after cord clamping, immediately after delivery. Activin A, hypoxanthine (Hx), xanthine (Xa) plasma levels and absolute nucleated red blood cell (NRBC) count were measured. Activin-A levels (p < 0.0001) and NRBC (p < 0.0001) were significantly higher in hypoxic than in non hypoxic preterm newborns. Cord activin A levels were significantly related with Hx (taua=0.64, taub=0.64, p < 0.0001) and Xa (taua=0.56, taub=0.57, p < 0.0001) levels, NRBC ((taua=-0.45, taub=-0.46, p < 0.0001) count; pH (taua=-0.47, taub=-0.48, p < 0.0001) and base deficit (taua=-0.36, taub=0.-0.36, p = 0.0002). Preterm newborns with signs of perinatal hypoxia at birth have increased activin-A levels, suggesting that activin-A may reflect indirectly intrauterine hypoxia.     

Sodium hypochlorite-, chlorine dioxide- and peracetic acid-induced genotoxicity detected by the Comet assay and Saccharomyces cerevisiae D7 tests

Mutagenicity of drinking water is due not only to industrial,agricultural and urban pollution but also to chlorine disinfectionby-products. Furthermore, residual disinfection is used to providea partial safeguard against low level contamination and bacterialre-growth within the distribution system. The aims of this studywere to further evaluate the genotoxic potential of the worldwide used disinfectants sodium hypochlorite and chlorine dioxidein human leukocytes by the Comet assay and in Saccharomycescerevisiae strain D7 (mitotic gene conversion, point mutationand mitochondrial DNA mutability, with and without endogenousmetabolic activation) and to compare their effects with thoseof peracetic acid, proposed as an alternative disinfectant.All three disinfectants are weakly genotoxic in human leukocytes(lowest effective dose 0.2 p.p.m. for chlorine dioxide, 0.5p.p.m. for sodium hypochlorite and peracetic acid). The resultsin S.cerevisiae show a genotoxic response on the end-pointsconsidered with an effect only at doses higher (5- to 10-fold)than the concentration normally used for water disinfection;sodium hypochlorite and peracetic acid are able to induce genotoxiceffects without endogenous metabolic activation (in stationaryphase cells) whereas chlorine dioxide is effective in growingcells. The Comet assay was more sensitive than the yeast tests,with effective doses in the range normally used for water disinfectionprocesses. The biological effectiveness of the three disinfectantson S.cerevisiae proved to be strictly dependent on cell-specificphysiological/biochemical conditions. All the compounds appearto act on the DNA and peracetic acid shows effectiveness similarto sodium hypochlorite and chlorine dioxide. ¹Author to whom correspondence should be addressed. Tel: +39 0521 905608; Fax: +39 0521 905604; Email: mutgen{at}unipr.it Received on September 22, 2003; revised and accepted on November 27, 2003     

Effects of cognitive remediation therapy on neurocognition and negative symptoms in schizophrenia: an Italian naturalistic study

Introduction: Cognitive remediation therapy (CRT) has been reported to positively affect neurocognitive processes among patients with schizophrenia; however, the degree to which changes in cognition is linked to improved clinical symptoms, remains poorly understood. The current study aimed to investigate whether cognitive gains were associated to improvements in negative symptoms’ severity in patients with schizophrenia living in two Italian psychiatric facilities.

Methods: Patients with a diagnosis of schizophrenia were consecutively assigned to CRT (n?=?33) and compared with an historical control group (n?=?28). Assessments were performed at baseline and post-treatment using a neuropsychological battery (Trail Making Test A and B, Self-Ordered Pointing Task, California Verbal Learning Test), along with clinical and functioning measures.

Results: Visual attention (TMT-A score change) was found as the only significant predictor of improvement in negative symptoms subscale of the Positive and Negative Syndrome Scale. Furthermore, a mediation path analysis confirmed that better performance in visual attention acts as mediator of the positive association between CRT intervention and lower post-treatment negative symptoms score.

Conclusions: CRT can have a positive impact on a measure of visual attention in patients with schizophrenia and on negative symptoms reduction that is mediated by this significant intervention effect.     

HIV-1 co-receptor usage: influence on mother-to-child transmission and pediatric infection

Viral CCR5 usage is not a predictive marker of mother to child transmission (MTCT) of HIV-1. CXCR4-using viral variants are little represented in pregnant women, have an increased although not significant risk of transmission and can be eventually also detected in the neonates. Genetic polymorphisms are more frequently of relevance in the child than in the mother. However, specific tissues as the placenta or the intestine, which are involved in the prevalent routes of infection in MTCT, may play an important role of selective barriers. The virus phenotype of the infected children, like that of adults, can evolve from R5 to CXCR4-using phenotype or remain R5 despite clinical progression to overt immune deficiency. The refined classification of R5 viruses into R5(narrow) and R5(broad) resolves the enigma of the R5 phenotype being associated with the state of immune deficiency. Studies are needed to address more in specific the relevance of these factors in HIV-1 MTCT and pediatric infection of non-B subtypes.     

A novel MEIS2 mutation explains the complex phenotype in a boy with a typical NF1 microdeletion syndrome

Concurrence of distinct genetic conditions in the same patient is not rare. Several cases involving neurofibromatosis type 1 (NF1) have recently been reported, indicating the need for more extensive molecular analysis when phenotypic features cannot be explained by a single gene mutation. Here, we describe the clinical presentation of a boy with a typical NF1 microdeletion syndrome complicated by cleft palate and other dysmorphic features, hypoplasia of corpus callosum, and partial bicoronal craniosynostosis caused by a novel 2bp deletion in exon 2 of Meis homeobox 2 gene (MEIS2) inherited from the mildly affected father. This is only the second case of an inherited MEIS2 intragenic mutation reported to date. MEIS2 is known to be associated with cleft palate, intellectual disability, heart defects, and dysmorphic features. Our clinical report suggests that this gene may also have a role in cranial morphogenesis in humans, as previously observed in animal models.     

Assessment of humoral and cellular immunity induced by the BNT162b2 SARS-CoV-2 vaccine in healthcare workers,elderly people,and immunosuppressed patients with autoimmune disease

The development of vaccines to prevent SARS-CoV-2 infection has mainly relied on the induction of neutralizing antibodies (nAbs) to the Spike protein of SARS-CoV-2, but there is growing evidence that T cell immune response can contribute to protection as well. In this study, an anti-receptor binding domain (RBD) antibody assay and an INFγ-release assay (IGRA) were used to detect humoral and cellular responses to the Pfizer-BioNTech BNT162b2 vaccine in three separate cohorts of COVID-19-naïve patients: 108 healthcare workers (HCWs), 15 elderly people, and 5 autoimmune patients treated with immunosuppressive agents. After the second dose of vaccine, the mean values of anti-RBD antibodies (Abs) and INFγ were 123.33 U/mL (range 27.55–464) and 1513 mIU/mL (range 145–2500) in HCWs and 210.7 U/mL (range 3–500) and 1167 mIU/mL (range 83–2500) in elderly people. No correlations between age and immune status were observed. On the contrary, a weak but significant positive correlation was found between INFγ and anti-RBD Abs values (rho = 0.354, p = 0.003). As to the autoimmune cohort, anti-RBD Abs were not detected in the two patients with absent peripheral CD19⁺B cells, despite high INFγ levels being observed in all 5 patients after vaccination. Even though the clinical relevance of T cell response has not yet been established as a correlate of vaccine-induced protection, IGRA testing has showed optimal sensitivity and specificity to define vaccine responders, even in patients lacking a cognate antibody response to the vaccine.

     

p53 Arg72Pro and MDM2 309 SNPs in hereditary retinoblastoma

The tumor suppressor p53 and its negative regulator MDM2 have crucial roles in a variety of cellular functions such as the control of the cell cycle, senescence, genome stability and apoptosis, and are frequently deregulated in carcinogenesis. Previous studies have highlighted the contribution of the common functional polymorphisms p53 p.Arg72Pro and MDM2 309SNP to the risk of both common cancers and Li-Fraumeni syndrome. Their possible role in retinoblastoma has recently been addressed by Castéra et al, who however only studied the MDM2 309SNP. Here, for the first time, we analyzed both single nucleotide polymorphisms (SNPs) in a case-control study of 111 Italian hereditary retinoblastoma patients. We found a significant association of the p53 Pro/Pro genotype with the disease (odds ratio=3.58, P=0.002). The MDM2 309SNP showed a weak negative association of allele G that deserves further investigation. These findings further support the hypothesis that genetic variability of the p53 pathway contributes to the individual susceptibility to retinoblastoma, as shown for Li-Fraumeni syndrome and a variety of non-hereditary cancers.