Mental health first aid training of the public in a rural area: a cluster randomized trial [ISRCTN53887541]

BACKGROUND: A Mental Health First Aid course has been developed which trains members of the public in how to give initial help in mental health crisis situations and to support people developing mental health problems. This course has previously been evaluated in a randomized controlled trial in a workplace setting and found to produce a number of positive effects. However, this was an efficacy trial under relatively ideal conditions. Here we report the results of an effectiveness trial in which the course is given under more typical conditions. METHODS: The course was taught to members of the public in a large rural area in Australia by staff of an area health service. The 16 Local Government Areas that made up the area were grouped into pairs matched for size, geography and socio-economic level. One of each Local Government Area pair was randomised to receive immediate training while one served as a wait-list control. There were 753 participants in the trial: 416 in the 8 trained areas and 337 in the 8 control areas. Outcomes measured before the course started and 4 months after it ended were knowledge of mental disorders, confidence in providing help, actual help provided, and social distance towards people with mental disorders. The data were analysed taking account of the clustered design and using an intention-to-treat approach. RESULTS: Training was found to produce significantly greater recognition of the disorders, increased agreement with health professionals about which interventions are likely to be helpful, decreased social distance, increased confidence in providing help to others, and an increase in help actually provided. There was no change in the number of people with mental health problems that trainees had contact with nor in the percentage advising someone to seek professional help. CONCLUSIONS: Mental Health First Aid training produces positive changes in knowledge, attitudes and behaviour when the course is given to members of the public by instructors from the local health service

Advances in structure elucidation of small molecules using mass spectrometry

The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules

Association of Hypercalcemia Before Treatment With Hypocalcemia After Treatment in Dogs With Primary Hyperparathyroidism.

BackgroundDevelopment of hypocalcemia after treatment of hyperparathyroidism results in increased costs and risk of poorer outcomes. Previous studies have shown conflicting data about predictors of hypocalcemia after these procedures.Hypothesis/objectivesThe objective of this study was to investigate whether ionized calcium (iCa) concentrations before treatment are predictive of hypocalcemia or its clinical signs after surgical removal or heat ablation in dogs with primary hyperparathyroidism.AnimalsFifty-four dogs with primary hyperparathyroidism (29 female, 25 male; 49 retrospective, 5 prospective).MethodsDogs were enrolled if they met the inclusion criteria: persistent hypercalcemia (iCa >1.41 mmol/L) due to primary hyperparathyroidism and absence of preemptive calcitriol treatment. All dogs were treated with parathyroidectomy (n = 37) or percutaneous ultrasound-guided heat ablation (n = 17). After treatment, iCa was monitored twice daily until plateau or intervention.ResultsThere was a moderate correlation between before-treatment hypercalcemia and after-treatment hypocalcemia. The prospective study was terminated due to ethical concerns given findings in the retrospective section. All dogs were placed into groups according to their pretreatment iCa: 1.46-1.61 mmol/L, 1.62-1.71 mmol/L, iCa 1.72-1.81 mmol/L, or >1.81 mmol/L. After treatment, the mean lowest iCa for each group, respectively, was 1.19, 1.18, 1.13, and 1.01 mmol/L. There was a significant association between higher group and proportion of dogs with iCa <1.00 mmol/L (P = .014).Conclusions and clinical importanceThis study demonstrates a moderate correlation between iCa concentration before treatment and hypocalcemia after treatment. Dogs with higher initial iCa concentrations should be treated to prevent rapid decline and development of clinical hypocalcemia

Association of Hypercalcemia Before Treatment With Hypocalcemia After Treatment in Dogs With Primary Hyperparathyroidism.

BackgroundDevelopment of hypocalcemia after treatment of hyperparathyroidism results in increased costs and risk of poorer outcomes. Previous studies have shown conflicting data about predictors of hypocalcemia after these procedures.Hypothesis/objectivesThe objective of this study was to investigate whether ionized calcium (iCa) concentrations before treatment are predictive of hypocalcemia or its clinical signs after surgical removal or heat ablation in dogs with primary hyperparathyroidism.AnimalsFifty-four dogs with primary hyperparathyroidism (29 female, 25 male; 49 retrospective, 5 prospective).MethodsDogs were enrolled if they met the inclusion criteria: persistent hypercalcemia (iCa >1.41 mmol/L) due to primary hyperparathyroidism and absence of preemptive calcitriol treatment. All dogs were treated with parathyroidectomy (n = 37) or percutaneous ultrasound-guided heat ablation (n = 17). After treatment, iCa was monitored twice daily until plateau or intervention.ResultsThere was a moderate correlation between before-treatment hypercalcemia and after-treatment hypocalcemia. The prospective study was terminated due to ethical concerns given findings in the retrospective section. All dogs were placed into groups according to their pretreatment iCa: 1.46-1.61 mmol/L, 1.62-1.71 mmol/L, iCa 1.72-1.81 mmol/L, or >1.81 mmol/L. After treatment, the mean lowest iCa for each group, respectively, was 1.19, 1.18, 1.13, and 1.01 mmol/L. There was a significant association between higher group and proportion of dogs with iCa <1.00 mmol/L (P = .014).Conclusions and clinical importanceThis study demonstrates a moderate correlation between iCa concentration before treatment and hypocalcemia after treatment. Dogs with higher initial iCa concentrations should be treated to prevent rapid decline and development of clinical hypocalcemia

Electrostatically-guided inhibition of Curli amyloid nucleation by the CsgC-like family of chaperones

Polypeptide aggregation into amyloid is linked with several debilitating human diseases. Despite the inherent risk of aggregation-induced cytotoxicity, bacteria control the export of amyloid-prone subunits and assemble adhesive amyloid fibres during biofilm formation. An Escherichia protein, CsgC potently inhibits amyloid formation of curli amyloid proteins. Here we unlock its mechanism of action, and show that CsgC strongly inhibits primary nucleation via electrostatically-guided molecular encounters, which expands the conformational distribution of disordered curli subunits. This delays the formation of higher order intermediates and maintains amyloidogenic subunits in a secretion-competent form. New structural insight also reveal that CsgC is part of diverse family of bacterial amyloid inhibitors. Curli assembly is therefore not only arrested in the periplasm, but the preservation of conformational flexibility also enables efficient secretion to the cell surface. Understanding how bacteria safely handle amyloidogenic polypeptides contribute towards efforts to control aggregation in disease-causing amyloids and amyloid-based biotechnological applications