The Role of Serotonin (5-HT) in Behavioral Control: Findings from Animal Research and Clinical Implications

The neurotransmitters serotonin and dopamine both have a critical role in the underlying neurobiology of different behaviors. With focus on the interplay between dopamine and serotonin, it has been proposed that dopamine biases behavior towards habitual responding, and with serotonin offsetting this phenomenon and directing the balance toward more flexible, goal-directed responding. The present focus paper stands in close relationship to the publication by Worbe et al. (2015), which deals with the effects of acute tryptophan depletion, a neurodietary physiological method to decrease central nervous serotonin synthesis in humans for a short period of time, on the balance between hypothetical goal-directed and habitual systems. In that research, acute tryptophan depletion challenge administration and a following short-term reduction in central nervous serotonin synthesis were associated with a shift of behavioral performance towards habitual responding, providing further evidence that central nervous serotonin function modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. In the present focus paper, we discuss the findings by Worbe and colleagues in light of animal experiments as well as clinical implications and discuss potential future avenues for related research.     

Monoclonal antibodies to the extracellular domain of HIV-1IIIB gp160 that neutralize infectivity, block binding to CD4, and react with diverse isolates.

Ten monoclonal antibodies prepared against a soluble, recombinant form of gp160, derived from the IIIB isolate of HIV-1, were characterized. Four of the antibodies neutralized HIV-1IIIB infectivity in vitro, three blocked the binding of recombinant gp120 to CD4, three were reactive with gp41, and one preferentially reacted with an epitope on gp120 within the gp160 precursor. All three CD4 blocking antibodies bound to distinct epitopes, with one mapping to the C1 domain, one mapping to the C4 domain, and one reactive with a conformation-dependent, discontinuous epitope. Of these, the antibody reactive with the discontinuous epitope exhibited neutralizing activity against homologous and heterologous strains of HIV-1. The binding of these monoclonal antibodies to a panel of seven recombinant gp120s prepared from diverse isolates of HIV-1 was measured, and monoclonal antibodies with broad cross reactivity were identified. The epitopes recognized by 7 of the 10 monoclonal antibodies studied were localized by their reactivity with synthetic peptides and with fragments of gp120 expressed as fusion proteins in a lambda gt-11 gp160 epitope library.     

Practical recommendations for the use of ACE inhibitors, beta-blockers, aldosterone antagonists and angiotensin receptor blockers in heart failure: putting guidelines into practice

Surveys of prescribing patterns in both hospitals and primary care have usually shown delays in translating the evidence from clinical trials of pharmacological agents into clinical practice, thereby denying patients with heart failure (HF) the benefits of drug treatments proven to improve well-being and prolong life. This may be due to unfamiliarity with the evidence-base for these therapies, the clinical guidelines recommending the use of these treatments or both, as well as concerns regarding adverse events. ACE inhibitors have long been the cornerstone of therapy for systolic HF irrespective of aetiology. Recent trials have now shown that treatment with beta-blockers, aldosterone antagonists and angiotensin receptor blockers also leads to substantial improvements in outcome. In order to accelerate the safe uptake of these treatments and to ensure that all eligible patients receive the most appropriate medications, a clear and concise set of clinical recommendations has been prepared by a group of clinicians with practical expertise in the management of HF. The objective of these recommendations is to provide practical guidance for non-specialists, in order to increase the use of evidenced based therapy for HF. These practical recommendations are meant to serve as a supplement to, rather than replacement of, existing HF guidelines.     

Prognosis of all-cause heart failure and borderline left ventricular systolic dysfunction: 5 year mortality follow-up of the Echocardiographic Heart of England Screening Study (ECHOES).

AIMS: Heart failure (HF) is reported to have an essentially malignant prognosis that can be modified by several interventions. Most outcome data on HF are available from randomized controlled treatment trials and longitudinal epidemiological studies. However, for a number of reasons, neither type of study have, to date, provided generalizable data on HF mortality. Furthermore, data on the prognosis of borderline left ventricular systolic dysfunction (LVSD) are even more limited. METHODS AND RESULTS: ECHOES (Echocardiographic Heart of England Screening Study) screened a total of 6,162 patients from a total of 10,161 invited (61% response rate). Patients were randomly selected from four pre-specified cohorts: the general population, diuretic users, those with a prior clinical label of HF, and a population with risk factors for HF, to identify the prevalence of HF and LVSD based on clinical assessment, ECG, and echocardiography. Causes of death during a 5-9 year follow-up period were recorded from routine mortality statistics. The 5-year survival rate of the general population was 93%, compared with 69% of those with LVSD without HF, 62% with HF and no LVSD, and 53% with HF plus LVSD. Survival improved significantly with increasing ejection fraction (EF) (log rank test for trend, chi(2) = 534.5, 1, P < 0.0001). CONCLUSION: The ECHOES mortality data confirm the poor prognosis of patients suffering prevalent HF across the community with a mortality risk estimate of 9% per year. Borderline systolic dysfunction (EF 40-50%) on echocardiography carries a poor prognosis.     

Antibodies to the five histones and poly(adenosine diphosphate-ribose) in drug induced lupus: implications for pathogenesis.

Certain drugs are a frequent source of antinuclear antibody (ANA) induction, and ANA is invariably present in the few patients who progress to the drug induced lupus syndrome. This report concerns the fine specificity of the ANA response to hydralazine, penicillamine, and sulphasalazine therapy. Using highly purified individual histones in fluorimetric assays, antihistone antibodies are always detectable, often in large amounts, but the pattern of response to individual histones is variable and not drug specific. In addition to the response to the three histones H1, H2B, and H3 reminiscent of idiopathic systemic lupus erythematosus, antibody to histone H2A predominates in some drug induced cases. Contrary to previous thought, histones are not the sole target of the antinuclear response: we also demonstrate a significant correlation between ANA titre and antibody to poly(adenosine diphosphate-ribose). Like the histones, this is a macromolecule that can bind to deoxyribonucleic acid (DNA). It is proposed that drug induced damage to chromatin leads to ANA production, while drug induced impairment of complement activity may then enable these autoantibodies to mediate the lupus syndrome.     

Perception of cancer recurrence risk: More information is better

Objective

Breast cancer is the most common cancer among women worldwide. Given the advances in extending survival, the number of recently diagnosed breast cancer patients and longer-term breast cancer survivors is growing. The goals of this study were to better understand (1) perceptions of provider cancer recurrence risk communication, (2) perceived risk of breast cancer recurrence in cancer patients and survivors, and (3) accuracy of perceived risk.

Methods

A survey was conducted on women with a prior breast cancer (n = 141).

Results

Approximately 40% of women perceived that providers had not talked about their breast cancer recurrence risk; although only 1 person reported not wanting a physician to talk to her about her risk. Women were largely inaccurate in their assessments of risk. Greater worry, living in a rural area, and longer time since diagnosis were associated with greater inaccuracy. Women tended to think about distal recurrence of cancer as often of local recurrence.

Conclusions

Perceived risk of breast cancer recurrence was inaccurate, and patients desired more communication about recurrence risk.

Practice implications

Consistent with findings from other studies, greater efforts are needed to improve the communication of cancer recurrence risk to patients. Attention should be paid to those from rural areas and to distal cancer recurrence in women with a previous history of breast cancer.     

Female Gender and Diabetes Mellitus Increase the Risk of Recurrence after Laparoscopic Incisional Hernia Repair

Background

Laparoscopic hernia repair is used widely for the repair of incisional hernias. Few case studies have focussed on purely ‘incisional’ hernias. This multicentre series represents a collaborative effort and employed statistical analyses to provide insight into the factors predisposing to recurrence of incisional hernia after laparoscopic repair. A specific hypothesis (ie, laterality of hernias as well as proximity to the xyphoid process and pubic symphysis predisposes to recurrence) was also tested.

Methods

This was a retrospective study of all laparoscopic incisional hernias undertaken in six centres from 1 January 2004 to 31 December 2010. It comprised a comprehensive review of case notes and a follow-up using a structured telephone questionnaire. Patient demographics, previous medical/surgical history, surgical procedure, postoperative recovery, and perceived effect on quality of life were recorded. Repairs undertaken for primary ventral hernias were excluded. A logistic regression analysis was then fitted with recurrence as the primary outcome.

Results

A total of 186 cases (91 females) were identified. Median follow-up was 42 months. Telephone interviews were answered by 115/186 (62%) of subjects. Logistic regression analyses suggested that only female sex (odds ratio (OR) 3.53; 95% confidence interval (CI) 1.39–8.97) and diabetes mellitus (3.54; 1–12.56) significantly increased the risk of recurrence. Position of the defect had no statistical effect.

Conclusions

These data suggest an increased risk of recurrence after laparoscopic incisional hernia repair in females and subjects with diabetes mellitus. These data will help inform surgeons and patients when considering laparoscopic management of incisional hernias. We recommend a centrally hosted, prospectively maintained national/international database to carry out additional research.     

A review of physical activity interventions on determinants of mental health in children and adolescents

The purpose of this article was to review the effects of physical activity (PA) lifestyle intervention on determinants of mental health among children and adolescents. A search was performed using the databases Academic Search Premier, CINHAL, EBSCOHost, PsycARTICLES and PsycINFO. Inclusion criteria were studies that utilized PA interventions designed to impact a determinant of mental health in a target population of 6–18 years. From this search, 537 results were identified and eight met the inclusion criteria. All studies reported an inverse relationship between PA and depression. Seven found a significant (p < 0.05) reduction in depression when various aerobic and/or resistance training exercises were introduced. Only one study found a negative correlation between very light intensity activity and determinants of psychological health (e.g. depression and anxiety); however, these results were not statistically significant. In conclusion, promoting PA appears to improve determinants of mental health, such as depression, global self-worth and self-efficacy. Recommendations for enhancing future interventions are presented.