Two novel genetic lesions and a common BH4-responsive mutation of the PAH gene in Italian patients with hyperphenylalaninemia

Hyperphenylalaninemia (HPA), due to a deficiency of phenylalanine hydroxylase (PAH) enzyme, is caused by mutations in the PAH gene. Molecular analysis in 23 Italian patients with PAH deficiency identified two novel (P281R, L287V) and 20 previously described genetic lesions in the PAH gene. The detection of the A403V amino acid substitution in combination with null mutations in patients with BH4-responsive PAH deficiency leads us to correlate it with BH4 responsiveness.     

Agricultural Leaders’ Influence on the Safety Culture of Workers

ABSTRACT

Most US farmers are small, independent owner-operators, many of whom are exempt from safety regulation and enforcement, as well as age restrictions relative to family members performing hazardous tasks. These smaller farms account for a disproportionate share of the total fatality and injury statistics from farming incidents, contributing to an agriculture-industry death rate that is seven times greater than all occupations combined. In contrast, large agricultural enterprises that employ larger numbers of non-family workers are more regulated and more highly incentivized by economic, supply chain, and societal factors to implement cultures of safety, and are more readily influenced by agricultural opinion leaders, agribusinesses, farm organizations, and agricultural media. These agricultural influencer institutions must find ways to play more significant roles in changing the culture on operations that use only family labor. They will find willing partners in safety organizations such as the Agricultural Safety and Health Council of America (ASHCA), Agricultural Extension, and other health and safety advocates, including the National Institute for Occupational Safety and Health (NIOSH)-funded agricultural research centers. The overall workplace injury statistics for agriculture remain alarming; however, with leadership from the larger farm operations, and help from ASHCA, academia, the healthcare community, and others, the current culture of workplace safety and health in agriculture can be impacted in positive ways.     

Symptomatologic analysis of psychotic and non-psychotic depression.

BACKGROUND: The aim of the present study is to evaluate the symptomatologic presentation of delusional compared to non-delusional major depressive episodes. METHODS: Two hundred and eighty-eight subjects suffering from mood disorder (144 bipolar, 133 unipolar) were assessed at admission by the Hamilton Depression Rating Scale (HAMD-21). RESULTS: Depressive symptomatology was more severe in the delusional sample, even after the exclusion of the items directly involved with delusional symptoms (P = 0.00002). CONCLUSIONS: Our data support the hypothesis of delusional depression as a more severe form of mood disorder.     

Tryptophan hydroxylase gene and response to lithium prophylaxis in mood disorders.

Lithium is an effective prophylactic agent in mood disorders but not all patients with mood disorders respond to lithium therapy; it is therefore necessary to identify responders prior to treatment. Clinical predictors account for about half of the variance and it is probable that genetic factors play a substantial role. The aim of this study was to investigate the possible association between the tryptophan hydroxylase (TPH) gene and prophylactic efficacy of lithium in mood disorders. One hundred and eight subjects affected by bipolar (n = 90) and major depressive (n = 18) disorder were followed prospectively for an average of 50.4 months and were typed for their TPH variant using polymerase chain reaction techniques. TPH variants were marginally associated with lithium outcome (F = 3.16; d.f.=2,105; P = 0.046). Subjects with the TPH*A/A variant showed a trend toward a worse response compared to both TPH*A/C and TPH*C/C variants. Consideration of possible stratification effects such as gender, polarity or age at onset did not influence the observed association. TPH variants may be a possible factor influencing the prophylactic efficacy of lithium in mood disorders.     

T cell response to myelin basic protein before and after treatment with interferon beta in multiple sclerosis.

Studies on the in vivo effects of interferon-beta (IFNbeta) therapy on autoreactive T cells have never been carried out in multiple sclerosis (MS). We investigated the T cell response to myelin basic protein (MBP), before and after IFN-beta therapy, raising MBP-specific T cell lines (TCL) from the peripheral blood of six MS patients with a satisfactory response to the treatment. IFNbeta did not affect the relative frequency and epitope specificity of the TCL. After IFNbeta therapy, the production of interleukin-4 was decreased in MBP-stimulated TCL while the secretion of interferon-gamma was increased in unstimulated TCL. Interleukin-10 and tumor necrosis factor-alpha did not show significant variations. This finding supports recent suggestions about the complexity of the T helper 1/T helper 2 paradigm in MS and other organ-specific autoimmune diseases. In fact, the beneficial effects of IFNbeta do not exclude an immunostimulatory action that may involve potentially autoreactive T cells. This has implications for future treatment options, including combination therapies.     

A multicentRE observational analysiS of PErsistenCe to Treatment in the new multiple sclerosis era: the RESPECT study

Journal of Neurology - In this independent, multicenter, retrospective study, we investigated the short-term persistence to treatment with first-line self-injectable or oral disease-modifying...     

PML risk is the main factor driving the choice of discontinuing natalizumab in a large multiple sclerosis population: results from an Italian multicenter retrospective study

Journal of Neurology - Natalizumab (NTZ) is an effective treatment for relapsing–remitting multiple sclerosis (RRMS). However, patients and physicians may consider discontinuing NTZ therapy...