The effects of difficulty and gain versus loss on vocal physiology and acoustics

To examine the basis of emotional changes to the voice, physiological and electroglottal measures were combined with acoustic speech analysis of 30 men performing a computer task in which they lost or gained points under two levels of difficulty. Predictions of the main effects of difficulty and reward on the voice were not borne out by the data. Instead, vocal changes depended largely on interactions between gain versus loss and difficulty. The rate at which the vocal folds open and close (fundamental frequency; fo) was higher for loss than for gain when difficulty was high, but not when difficulty was low. Electroglottal measures revealed that fo changes corresponded to shorter glottal open times for the loss conditions. Longer closed and shorter open phases were consistent with raised laryngeal tension in difficult loss conditions. Similarly, skin conductance indicated higher sympathetic arousal in loss than gain conditions, particularly when difficulty was high. The results provide evidence of the physiological basis of affective vocal responses, confirming the utility of measuring physiology and voice in the study of emotion.     

A case of slipped capital femoral epiphysis results from hypophosphatemic rickets： treatment and midterm follow-up

In this case, a male patient presented with a clinically and radiographieally unstable slipped capital femoral epiphysis （SCFE） as well as slipped calcaneal epiphysis years. Subsequent thorough at the age of 23 work-up revealed that he had some features of rickets and labo- ratory test demonstrated he had hypophos- phatemia （2.3mg/dl）, normocalcemia, normal vi- tamin D metabolite levels, and secondary hy- perparathyroidism.     

Neuronal Nitric Oxide Synthase (NOS1) Polymorphisms Interact with Financial Hardship to Affect Depression Risk

There is increasing evidence that genetic factors have a role in differential susceptibility to depression in response to severe or chronic adversity. Studies in animals suggest that nitric oxide (NO) signalling has a key role in depression-like behavioural responses to stress. This study investigated whether genetic variation in the brain-expressed nitric oxide synthase gene NOS1 modifies the relationship between psychosocial stress and current depression score. We recruited a population sample of 1222 individuals who provided DNA and questionnaire data on symptoms and stress. Scores on the List of Life-Threatening Experiences (LTE) questionnaire for the last year and self-rated current financial hardship were used as measures of recent/ongoing psychosocial stress. Twenty SNPs were genotyped. Significant associations between eight NOS1 SNPs, comprising two regional haplotypes, and current depression score were identified that survived correction for multiple testing when current financial hardship was used as the interaction term. A smaller three-SNP haplotypes (rs10507279, rs1004356 and rs3782218) located in a regulatory region of NOS1 showed one of the strongest effects, with the A-C-T haplotype associating with higher depression scores at low adversity levels but lower depression scores at higher adversity levels (p=2.3E-05). These results suggest that NOS1 SNPs interact with exposure to economic and psychosocial stressors to alter individual''s susceptibility to depression.     

Combination therapy of established cancer using a histone deacetylase inhibitor and a TRAIL receptor agonist

Histone deacetylase inhibitors (HDACi) and agents such as recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and agonistic anti-TRAIL receptor (TRAIL-R) antibodies are anticancer agents that have shown promise in preclinical settings and in early phase clinical trials as monotherapies. Although HDACi and activators of the TRAIL pathway have different molecular targets and mechanisms of action, they share the ability to induce tumor cell-selective apoptosis. The ability of HDACi to induce expression of TRAIL-R death receptors 4 and 5 (DR4/DR5), and induce tumor cell death via the intrinsic apoptotic pathway provides a molecular rationale to combine these agents with activators of the TRAIL pathway that activate the alternative (death receptor) apoptotic pathway. Herein, we demonstrate that the HDACi vorinostat synergizes with the mouse DR5-specific monoclonal antibody MD5-1 to induce rapid and robust tumor cell apoptosis in vitro and in vivo. Importantly, using a preclinical mouse breast cancer model, we show that the combination of vorinostat and MD5-1 is safe and induces regression of established tumors, whereas single agent treatment had little or no effect. Functional analyses revealed that rather than mediating enhanced tumor cell apoptosis via the simultaneous activation of the intrinsic and extrinsic apoptotic pathways, vorinostat augmented MD5-1-induced apoptosis concomitant with down-regulation of the intracellular apoptosis inhibitor cellular-FLIP (c-FLIP). These data demonstrate that combination therapies involving HDACi and activators of the TRAIL pathway can be efficacious for the treatment of cancer in experimental mouse models.     

Intestinal obstruction promotes gut translocation of bacteria

PURPOSE: Translocation of enteric organisms has been implicated as a possible source of sepsis in susceptible patients. Animal studies have suggested that intestinal obstruction promotes bacterial translocation from the gut lumen. The aim of this study was to study the prevalence of bacterial translocation in patients with and without intestinal obstruction. METHODS: Serosal scrapings, mesenteric lymph nodes, and peripheral blood cultures were obtained from 254 patients. Scrapings and nodes were homogenized and incubated aerobically and anaerobically. Full-thickness biopsies underwent villous height analysis. The clinical course was followed for at least six weeks. RESULTS: Bacterial translocation to mesenteric nodes occurred more frequently in patients with large bowel obstruction than in patients without obstruction (14 of 36 patients vs.16 of 218 patients;P<0.001). Both aerobic and anaerobic bacteria were found to translocate. The more distal the obstruction, the more likely anaerobic bacteria were to be identified. Translocation of bacteria predisposed to postoperative septic complications (P<0.05). Villous height was not related to bacterial translocation. CONCLUSIONS: Gut translocation of bacteria is more common in patients with intestinal obstruction, and its association with septic complications appears to be of clinical significance.Supported by the Yorkshire Regional Health Authority Research Trust, Harrogate, United Kingdom.Read at the meeting of The American Society of Colon and Rectal Surgeons, Orlando, Florida, May 8 to 13, 1994.     

A randomized study of high-dose cytarabine in induction in acute myeloid leukemia [see comments]

High-dose cytarabine (ara-c) may overcome cytarabine resistance in leukemic blasts. It has been used as a successful salvage and in postremission therapy but not as initial induction treatment. Patients aged 15 to 60 years, presenting with newly diagnosed acute myeloid leukemia (AML) were randomized to receive either high-dose cytarabine, 3 g/m2 12 hourly on days 1, 3, 5, and 7 for 8 doses, daunorubicin 50 mg/m2 days 1 to 3, etoposide 75 mg/m2 days 1 to 7, (HIDAC-3-7) or standard dose cytarabine 100 mg/m2 continuous intravenous infusion for 7 days with daunorubicin and etoposide at the same dose and schedule as above (7-3-7). Patients could receive a second or third induction course if complete remission (CR) was not achieved. All patients received the same postinduction consolidation therapy (5-2-5) for 2 courses. Eligible patients had no prior chemotherapy or myelodysplastic disease. Patients have been followed for a median of 4.5 years. Of 301 patients treated, complete response (CR) was achieved in 71% with HIDAC- 3-7 and 74% with 7-3-7. For patients in CR, the estimated median remission duration was 45 months with HIDAC-3-7 and 12 months with 7-3- 7 (P = .0005 univariate analysis, P = .0004 multivariate analysis). The estimated percentage of patients relapse free 5 years after achieving a CR was 49% on HIDAC-3-7 and 24% on 7-3-7. Patients in CR tended to survive longer with HIDAC-3-7 but there were no overall survival differences between the two arms. HIDAC-3-7 was associated with significantly more toxicity in induction with more leukopenia, thrombocytopenia, nausea, and vomiting and eye toxicity (all P < .001) but a similar incidence of severe central nervous system and cerebellar toxicity compared to 7-3-7. The consolidation treatment was the same in both arms but caused significantly more leukopenia and thrombocytopenia in patients previously treated with HIDAC-3-7 induction (P < .0001). We conclude that a dose-effect exists for cytarabine in AML and that HIDAC- 3-7 prolongs remission duration and disease-free survival and is tolerable when used as initial induction therapy in patients with de novo AML.     

The value of prognostic indices for pneumonia

One of the most important decisions in the management of community-acquired pneumonia is deciding the care site, which affects morbidity, mortality, and costs. Clinical judgment alone is difficult and imprecise. The Pneumonia Severity Index score and the CURB-65 (confusion, urea nitrogen, respiratory rate, blood pressure, 65 years of age and older) score are validated prognostic indices to predict mortality, and they can identify low-risk patients who may be eligible for outpatient management. However, limitations of the scoring systems preclude their isolated use, and they can only be recommended as an aid to guide hospital admission decisions. The Pneumonia Severity Index score is slightly better at identifying the lowest risk patients, whereas CURB-65 is much simpler to use. As an adjunct to clinical judgment, we consider CURB-65 to be the most useful prognostic index for identifying low-risk patients.