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OBJECTIVES: Identifying factors predictive of long-term morbidity should improve clinical planning limiting disability and mortality associated with bipolar disorder (BD). METHODS: We analyzed factors associated with total, depressive and mania-related long-term morbidity and their ratio D/M, as %-time ill between a first-lifetime major affective episode and last follow-up of 207 BD subjects. Bivariate comparisons were followed by multivariable linear regression modeling. RESULTS: Total % of months ill during follow-up was greater in 96 BD-II (40.2%) than 111 BD-I subjects (28.4%; P=0.001). Time in depression averaged 26.1% in BD-II and 14.3% in BD-I, whereas mania-related morbidity was similar in both, averaging 13.9%. Their ratio D/M was 3.7-fold greater in BD-II than BD-I (5.74 vs. 1.96; P<0.0001). Predictive factors independently associated with total %-time ill were: [a] BD-II diagnosis, [b] longer prodrome from antecedents to first affective episode, and [c] any psychiatric comorbidity. Associated with %-time depressed were: [a] BD-II diagnosis, [b] any antecedent psychiatric syndrome, [c] psychiatric comorbidity, and [d] agitated/psychotic depressive first affective episode. Associated with %-time in mania-like illness were: [a] fewer years ill and [b] (hypo)manic first affective episode. The long-term D/M morbidity ratio was associated with: [a] anxious temperament, [b] depressive first episode, and [c] BD-II diagnosis. CONCLUSIONS: Long-term depressive greatly exceeded mania-like morbidity in BD patients. BD-II subjects spent 42% more time ill overall, with a 3.7-times greater D/M morbidity ratio, than BD-I. More time depressed was predicted by agitated/psychotic initial depressive episodes, psychiatric comorbidity, and BD-II diagnosis. Longer prodrome and any antecedent psychiatric syndrome were respectively associated with total and depressive morbidity.

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Cell fate decisions are controlled by the interplay of transcription factors and epigenetic modifiers, which together determine cellular identity. Here we elaborate on the role of miR302 in the regulation of cell plasticity. Overexpression of miR302 effected silencing of the TGFß type II receptor and facilitated plasticity in a manner distinct from pluripotency, characterized by increased expression of Snail. miR302 overexpressing mesangial cells also exhibited enhanced expression of EZH2 coincident with Snail upregulation. esiRNA silencing of each component suggest that Smad3 and EZH2 are part of a complex that regulates plasticity and that miR302 regulates EZH2 and Snail independently. Subsequent manipulation of miR302 overexpressing cells demonstrated the potential of using this approach for reprogramming as evidenced by de novo expression of the tight junction components ZO-1 and E-cadherin and the formation of ZO-1 containing tight junctions. Understanding the processes through which dynamic epigenetic silencing is controlled in adults cells will allow us to address the epigenetic state of acquired disease and whether original states, regenerative in nature, can be restored with therapy.

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BACKGROUND: Menarche age has been associated inconsistently with the occurrence, timing or severity of major depressive disorder (MDD), but rarely studied in women with bipolar (BDs) or anxiety disorders. METHODS: We investigated women patients at a Sardinian mood disorder center for associations of age at menarche with age at illness onset for major affective or anxiety disorders, year of birth, and other selected factors, using bivariate comparisons and multivariate regression modeling. RESULTS: Among women (n=1139) with DSM-IV MDD (n=557), BD-I (n=223), BD-II (n=178), or anxiety disorders (n=181), born in 1904-1998, of mean age 42.9 years, menarche age averaged 12.8 [CI: 12.7-12.9] years. Illness onset age averaged 30.9 [30.1-31.8] years, ranking: BD-I, 25.8; anxiety disorders, 28.0; BD-II, 30.3; MDD, 34.1 years. Menarche age declined secularly over birth years, and was associated with younger illness-onset, having no or fewer siblings, more psychiatrically ill first-degree relatives, living in rural environments, being suicidal, substance abuse, and being unemployed. Earlier menarche and earlier illness-onset were significantly associated for onset age groups of ≤ 20, 20-39, and > 40 years. Menarche age versus diagnosis ranked: BD-II

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BACKGROUND: The development of specific screening programs for individuals with a family history of colorectal cancer (CRC) is a priority. This study evaluates the diagnostic performance of serum soluble CD26 (sCD26) in family-risk individuals and compares this marker with the faecal immunochemical test for the detection of advanced neoplasia (AN) (CRC or advanced adenomas; AA). METHODS: Five hundred and sixteen asymptomatic individuals with at least one first-degree relative with CRC were included. Serum sCD26 was measured in all the individuals who also underwent a colonoscopy (53 AA and four cancer cases were found) and a faecal immunochemical test. RESULTS: Setting specificity to 90% and 95%, respectively, sCD26 showed a sensitivity of 39.6% and 28.3% for AA, and of 42.1% and 28.1% for AN. The combination of sCD26 and the faecal test detected AA and AN with a 52.8% and 56.1% sensitivity, corresponding to 93.5% specificity. CONCLUSIONS: The combination of serum sCD26 and the faecal blood test could result a valuable strategy for detecting AN in familial-risk CRC screening.

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OBJECTIVE: The aim of the Study was to compare the impacted third molar surgical technique by means of the high speed rotary handpiece with the piezoelectric one. MATERIALS AND METHODS: 192 patients have been selected among those who had to undergo a third molar surgical extraction. These patients' surgeries have been performed by means of one of the techniques, randomly chosen. Each patient has undergone the same analgesic therapy (paracetamol 1000 mg tablets). Each surgery has been performed by the same surgeon. The patients were asked to fill in a questionnaire concerning the postoperative pain ("happy face pain" rating scale). RESULTS: The average duration of the surgeries performed by means of the high speed rotary handpiece was 32 minutes, while the duration of the ones performed by means of the piezoelectric handpiece was much longer (54 minutes). The postoperative pain values were almost equal. CONCLUSIONS: In conclusion, the osteotomy performed by means of the traditional technique still represents the gold standard in the impacted third molar surgery. The piezoelectric technique may be an effective choice, especially for the less skilled surgeons, in order to guarantee the protection of the delicate locoregional anatomical structures.

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The cyclic AMP phosphodiesterase (PDE) activity in Leishmania mexicana is mainly located (>95%) in the soluble fraction of the cell. The intact parasite, as well as plasma membranes, showed PDE activity, probably indicating that at least part of the activity in the particulate fraction resides on the parasite cell surface, with its catalytic domain facing the extracellular moiety. For the first time, a highly specific cAMP phosphodiesterase (PDE) was purified from the soluble fraction to apparent homogeneity after a single step 2239-fold purification using pseudo-affinity chromatography on Cibacron Blue 3GA agarose. The enzyme was identified as a 61-kDa protein on SDS-PAGE, with a K(m) of 277 microM at 30 degrees C (optimum temperature). The native enzyme protein showed an apparent molecular size of approximately 200000 estimated by molecular sieve chromatography on Sephacryl S-300. Further characterization of the PDE activity present in the soluble fraction shows that the enzyme requires Mg(2+) for maximal activity. Furthermore, no activity was detected when assayed at pHs below 6.0, but above this value it increased dramatically, reaching the optimum at pH 7.2. On the basis of the K(m) and PDE activity in presence of specific drugs or modulators such as rolipram, OPC-3911, cGMP, IBMX, zaprinast, theophylline, caffeine and Ca(2+)/calmodulin, this enzyme does not seem to conform to any of the ten previously described Class I PDE families but to the PDE class II (or non-mammalian PDEs) similar to the those found in Candida albicans, Dictyostelium discoideum, Saccharomyces cerevisiae or Vibrio fischeri.

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