How do genes exert their role? Period 3 gene variants and possible influences on mood disorder phenotypes

The action of multiple liability genes is responsible for complex phenotypes at the same time, a single gene, could control several phenotypic features. This is the case of human period 3 gene (hper3), mainly involved in the setting of the biologic clock. Some variants of this gene, besides being associated with the Delayed Sleep Phase Syndrome, showed a key role in determining evening preference rather than morning one. According to this rationale, we hypothesized that this gene could influence circadian mood fluctuations, in mood disorders. Our study demonstrated that rare genetic variants of hper3 are significantly associated to a number of mood disorders features, such as age of onset, response to SSRIs treatment, circadian mood oscillations and characteristics of temperament. These preliminary results could shed further light on the involvement of circadian genes in various aspects of physiological and psychopathological mechanisms of the brain.     

RESPONSIVENESS AND SENSITIVITY TO CHOLINERGIC AGONISTS AND ANTAGONISTS IN BOVINE ISOLATED BRONCHIAL MUSCLE

1. Airways derived from different levels of the lung exhibit a difference in the reactivity and sensitivity to agonists. We have evaluated the effect of acetylcholine and cholinergic selective (pirenzepine, gallamine and 4-dipherylacetoxymethyl piperidine [4-DAMP]) and non-selective (atropine) antagonists on bovine proximal and distal smooth muscle preparations. 2. The distal preparations are more sensitive to acetylcholine than proximal bronchi. The relaxant effect of three selective antagonists on the distal and proximal tissues was the same when the results for each drug were compared. 3. Atropine and 4-DAMP were more potent than pirenzepine and gallamine in relaxing both proximal and distal bovine smooth muscle preparations. 4. These data suggest that the muscarinic sites on the smooth muscle of bovine airways are of the M3 subtype.     

Prognostic value of pharmacological stress echocardiography in diabetic and nondiabetic patients with known or suspected coronary artery disease.

OBJECTIVES: We sought to compare the prognostic value of pharmacological stress echocardiography (SE) in diabetic and nondiabetic patients with known or suspected coronary artery disease. BACKGROUND: Although SE is a useful tool for risk stratification of patients with diabetes, it has not been established whether it retains the same prognostic information in diabetic patients compared with nondiabetic patients. METHODS: A total of 5,456 patients (749 diabetics) undergoing dipyridamole (n = 3,306) or dobutamine (n = 2,150) SE were prospectively followed up for the occurrence of hard events (death and/or nonfatal myocardial infarction). RESULTS: During a median time of 31 months, 411 deaths and 236 infarctions occurred. There were 132 events in diabetic patients and 515 in nondiabetic patients (18% vs. 11%, respectively; p < 0.0001). Moreover, 1,607 (29%) patients underwent coronary revascularization and were censored. Ischemia at SE, resting wall motion score index, and age were independent predictors of death and hard events in both diabetic and nondiabetic patients. Compared with a normal test, ischemia and scar test patterns were associated to significantly lower age-corrected five-year hard event-free survival in diabetic as well as nondiabetic patients. However, a normal test was associated with a greater than two-fold annual event rate in diabetic patients as compared with nondiabetics who were either younger (2.6% vs. 1.0%) or older (5.5% vs. 2.2%) than 65 years of age. CONCLUSIONS: Stress echocardiography is equally effective in risk stratifying diabetic and nondiabetic patients independently of age. However, the normal test result predicts a less favorable outcome in diabetic than in nondiabetic patients.     

Low molecular weight advanced glycation end products predict mortality in asymptomatic patients receiving chronic haemodialysis.

BACKGROUND: Advanced glycation end products (AGEs) have biological properties that may contribute to the premature cardiovascular mortality of haemodialysis patients. This study examines the hypothesis that low molecular weight forms of fluorescent AGEs (LMW fluorescence) predict mortality in haemodialysis patients. METHODS: The LMW fluorescence was measured in 85 patients treated with chronic haemodialysis and prospectively followed for 4 years. The primary outcome of all-cause mortality was assessed using Cox proportional hazards regression model. RESULTS: At the end of the follow-up period 37 (44%) patients died. The median LMW fluorescence level was 24.2 arbitrary units (range: 10.6-148.1 AU) and the receiver operator characteristic (ROC) curve cut-off for mortality was 37.0 AU. The LMW fluorescence predicted death both as a binary variable at the ROC cut-off, and as a continuous log-transformed variable when adjusted for age, albumin and C-reactive protein (CRP). Adjusted for age, albumin and CRP, the hazard ratio for mortality was 3.05 (1.41-6.60, P = 0.005) for LMW fluorescence as a binary variable and 2.71 per log unit (1.37-5.38, P = 0.004) as a continuous log-transformed variable. CONCLUSION: The low molecular weight forms of AGEs predict mortality in patients receiving chronic haemodialysis, and may be important in the mechanisms leading to atherosclerosis and inflammation in such patients.     

Knee-ankle-foot orthosis in children with duchenne muscular dystrophy: user views and adjustment.

BACKGROUND: The use of knee ankle foot orthoses (KAFOs) to prolong independent mobility is a widely used rehabilitation strategy for children with Duchenne muscular dystrophy (DMD). AIMS: To explore views and adjustment of families with a child with Duchenne muscular dystrophy to the use of KAFOs. METHODS: interviews with families of children aged 8-18 years with DMD; questionnaires on psychiatric adjustment (SDQ for children; GHQ for parents). RESULTS: In total, 17 parents and 9 children took part. Families experienced the introduction of KAFOs as a signal for illness deterioration and a re-awakening of the feelings experienced at diagnosis. Nevertheless, the majority expressed a positive attitude and over two-thirds satisfaction with KAFOs use. High psychiatric risk was found in 2/17 children (12%; expected 10%) and 7/17 main carers (41%; expected 20-30%). CONCLUSION: Most families were satisfied with KAFOs use, and its implementation was well tolerated especially by the children. However, mental distress was high in main carers who emphasized the importance of full preparation and support in this rehabilitation technique.     

Systemic fungemia and hepatic localizations of Fusarium solani in a liver transplanted patient: an emerging fungal agent.

The incidence of invasive fungal infection is increasing especially in the field of transplantation, affecting as many as 50% of bone marrow transplant (BMT) patients with neutropenia and 5-20% of solid-organ transplant (SOT) recipients. Fusarium species are soil saprophytes and plant pathogens. They may cause superficial mycoses or important opportunistic infections in patients with bone marrow suppression and neutropenia, they have been rarely described in solid organ recipients, and up to now there have been no reports of such infection in isolated liver transplanted patients. We describe a case of disseminated Fusarium solani infection with hepatic localization in a liver transplanted patient that resolved with the administration of amphotericin B. Our observation confirms that Fusarium spp. are emerging pathogens that may most frequently affect not only BMT patients and patients with hematological malignancies, but also SOT patients. They may cause both localized and disseminated infection. In conclusion, Fusarium spp. etiology should be considered in the context of infectious diseases following liver transplantation.     

Surgical treatment of Aspergillus mycetomas of the maxillary sinus: review of the literature.

The present study reviews the literature concerning the surgical treatment of Aspergillus mycetoma (AM) in the last 20 years to identify a gold standard surgical technique. Aspergillus mycetoma of the maxillary sinus, or mycetoma (fungus ball), is a noninvasive or extramucosal mycotic infection. Surgical removal of the sinus fungal masses to ensure drainage and aeration is performed using the traditional Caldwell-Luc (CL) procedure or endoscopic sinus surgery (ESS). Results of this review suggest that the gold standard surgical technique for AM is ESS with middle meatal antrostomy. General or local antifungal drugs are not indicated. Combined approach with an intraoral surgical access from the anterolateral wall of the maxillary sinus has to be reserved for selected cases in which ESS doesn't permit complete extraction of all fungal concretions or foreign bodies. The CL procedure should be avoided, because it has detrimental consequences for sinus physiology.