The Temple Vie weight management and lifestyle programme: initial data and reflections on Covid-19.

During the first three months of the Temple Vie programme, average weight loss in 36 subjects exceeded 13 kg. There were associated improvements in Patient Reported Outcome Measures, blood pressure and serum lipids. The Covid-19 pandemic may focus attention on programmes that give rise to rapid weight loss and improvements in cardiovascular health parameters.

Relatedness of medically important strains of Saccharomyces cerevisiae as revealed by phylogenetics and metabolomics.

Ten medically important Saccharomyces strains, comprising six clinical isolates of Saccharomyces cerevisiae and four probiotic strains of Saccharomyces boulardii, were characterized at the genetic and metabolic level and compared with non-medical, commercial yeast strains used in baking and wine-making. Strains were compared by genetic fingerprinting using amplified fragment length polymorphism (AFLP) analysis, by ribosomal DNA ITS1 sequencing and by metabolic footprinting using both direct injection mass spectrometry (DIMS) and gas chromatography-time of flight-mass spectrometry (GC-ToF-MS). Overall, the clinical isolates fell into different groupings when compared with the non-medical strains, with good but not perfect correlation amongst strains at both the genetic and metabolic levels. Probiotic strains of S. boulardii that are used therapeutically to treat human gastro-intestinal tract disorders showed tight clustering both genetically and metabolically. Metabolomics was found to be of value both as a taxonomic tool and as a means to investigate anomalous links between genotype and phenotype. Key discriminatory metabolites were identified when comparing the three main groups of clinical, probiotic and non-medical strains and included molecules such as trehalose, myo-inositol, lactic acid, fumaric acid and glycerol 3-phosphate. This study confirmed the link between a subset of clinical isolates and baking or probiotic strains but also highlighted that in general the clinical strains were more diverse at both the genomic and metabolic levels.

Acute effect of poly-gamma-glutamic acid on calcium absorption in post-menopausal women.

OBJECTIVE: Poly-gamma-glutamic acid (PGA) increases calcium (Ca) solubility in vitro and in vivo, and is associated with reduced bone loss in post-menopausal Japanese women. This study is the first to examine the effect of PGA on Ca absorption in humans. METHODS: A single-blind, randomized, crossover study with a 3-4 week wash-out was performed to determine the effect of PGA (80.6% glutamic acids) on Ca absorption measured by the double stable isotope method. Twenty-four healthy, non-smoking, postmenopausal women (mean age: 56.4 +/- SE 0.9) were given 200 g of orange juice containing 200 mg Ca as Ca-44 enriched CaCO(3), with or without 60 mg of PGA, after an overnight fast. The two tests were separated by 3-4 weeks. An intravenous injection of Ca-42 (CaCl(2) solution) was given 30 min after consuming the drink and a complete urine collection carried out from 24-48 h post-dosing. Ca absorption was calculated from the Ca isotope ratios measured by thermal ionization quadrupole mass spectrometry (TIQMS). RESULTS: Mean Ca absorption with PGA was significantly higher (P < 0.01) than without PGA, 39.1 (SE 1.6) % and 34.6 (SE 1.9) %, respectively. The effect of PGA on increasing Ca absorption was more marked in a sub-group of subjects whose baseline Ca absorption (without PGA) was lower than the population mean value. CONCLUSION: Postmenopausal women who received a single dose of PGA increased their intestinal Ca absorption particularly those individuals with lower basal absorptive capacity.

Dates of birth and seasonal changes in well-being among 4904 subjects completing the seasonal pattern assessment questionnaire.

BACKGROUND: Abnormal distributions of birthdates, suggesting intrauterine aetiological factors, have been found in several psychiatric disorders, including one study of out-patients with Seasonal Affective Disorder (S.A.D.). We investigated birthdate distribution in relation to seasonal changes in well-being among a cohort who had completed the Seasonal Pattern Assessment Questionnaire (SPAQ). METHOD: A sample of 4904 subjects, aged 16 to 64, completed the SPAQ. 476 were cases of S.A.D. on the SPAQ and 580 were cases of sub-syndromal S.A.D. (S-S.A.D.). 92 were interview confirmed cases of S.A.D. Months and dates of birth were compared between S.A.D. cases and all others, between S.A.D. and S-S.A.D. cases combined and all others, and between interview confirmed cases and all others. Seasonality, as measured through seasonal fluctuations in well-being on the Global Seasonality Scores (GSS) of the SPAQ, was compared for all subjects by month and season of birth. RESULTS: There was no evidence of an atypical pattern of birthdates for subjects fulfilling criteria for S.A.D., for the combined S.A.D./S-S.A.D. group or for interview confirmed cases. There was also no relationship between seasonality on the GSS and month or season of birth. LIMITATIONS: Diagnoses of S.A.D. made by SPAQ criteria are likely to be overinclusive. CONCLUSION: Our findings differ from studies of patients with more severe mood disorders, including psychiatric out-patients with S.A.D. The lack of association between seasonality and birthdates in our study adds credence to the view that the aetiology of S.A.D. relates to separable factors predisposing to affective disorders and to seasonality.

Identification and quantification of glucosinolates in sprouts derived from seeds of wild Eruca sativa L. (salad rocket) and Diplotaxis tenuifolia L. (wild rocket) from diverse geographical locations.

The Brassicaceae rocket species Eruca sativa L. (salad rocket) and Diplotaxis tenuifolia L. (wild rocket) are consumed throughout the world in salads, predominantly the leaves but also the flowers and more recently the sprouts (seedlings). Ontogenic profiling of glucosinolates and flavonoids in plants derived from commercial seed of these species has previously been done, but no studies have been conducted to determine how geographical origin affects glucosinolate composition in rocket species. Seeds from wild E. sativa L. and D. tenuifolia L. from diverse regions of the world were obtained from gene banks and grown under controlled conditions. Sprouts were harvested when they would normally be harvested for consumption, and glucosinolates were extracted and profiled in these accessions. All of the sprouts from Italian E. sativa L. had consistently high total glucosinolate content, with only a few exceptions, and also the highest percentage contents of 4-mercaptobutylglucosinolate. In contrast, sprouts produced from Central and Eastern European seeds had a much higher percentage of 4-methylthiobutylglucosinolate. With a single exception, Tunisia, all sprouts produced from North African seeds had very high 4-methylthiobutylglucosinolate contents. The single sample from China had a high total glucosinolate content and glucosinolate profile that was very similar to the accessions from Uzbekistan and Pakistan. All of the D. tenuifolia L. sprouts had consistently high total glucosinolate contents, and a high percentage of this was 4-mercaptobutylglucosinolate. This glucosinolate variation in levels and profiles of the rockets can be used for genetic studies, selected breeding, and human intervention studies.

Anorexia nervosa mortality in Northeast Scotland, 1965-1999.

OBJECTIVE: Most previous studies of mortality in anorexia nervosa patients have shown an increased risk of premature death but have been limited by methodological constraints. This study aimed to overcome some of these constraints by having a large original sample size, diagnosis confirmed by case note review, a long duration of follow-up, and a clear base population. METHOD: The authors identified 524 anorexia nervosa cases seen in specialist services in Northeast Scotland; anorexia nervosa diagnosis was confirmed by scrutinizing case notes. Those who had died were identified from the National Health Service register or register of deaths. The death rates and causes of death were analyzed. RESULTS: Twenty-three patients died, giving a crude death rate of 4.4% and a standardized mortality rate of 3.3 (95% CI=2.2-4.9). In only one-third of the cases was anorexia nervosa on the death certificate, but an eating disorder or other psychiatric pathology probably contributed to several of the other deaths. Older age at the time the patient was seen at the specialist service was the only identifiable risk factor in the group of patients who died. The median length of time between diagnosis and death was 11 years. CONCLUSIONS: Anorexia nervosa is associated with increased risk of premature death. It is possible that death rates could be reduced by early diagnosis and by long-term specialist care.

A placebo-controlled study of sertraline in the treatment of outpatients with seasonal affective disorder.

RATIONALE: Seasonal affective disorder (SAD) is a relatively common cyclical depressive illness characterized by seasonal depressions during winter. The disorder is commonly responsive to light therapy, but antidepressant drug efficacy has not been definitely established. Serotonin selective re-uptake inhibitors are potentially efficacious treatments for SAD. OBJECTIVES: The objective of this study was to evaluate the efficacy, tolerability and safety of sertraline treatment for SAD. METHODS: One hundred and eighty seven outpatients with seasonal pattern recurrent winter depression (DSM-III-R defined) and a minimum 29-item Hamilton depression scale (SIGH-SAD version) score of 22 were randomized to 8 weeks treatment with either sertraline or placebo in a double-blind, multi-country, multi-center, parallel-group, flexible dose (50-200 mg once daily) study. Efficacy was investigated using physician and patient-rated scales measuring depression, anxiety and symptoms characteristic of seasonal affective disorder. RESULTS: Sertraline produced a significantly greater response than placebo at endpoint as measured by changes in the 29-item and 21-item Hamilton depression scales, the clinical global impression (CGI) severity scale, the Hamilton anxiety scale, and the hospital anxiety and depression scale. The proportion of sertraline-treated subjects achieving a response on the CGI improvement rating (ratings of 1 or 2) at endpoint (last observation carried forward) was significantly greater than that of the placebo group. Overall sertraline was well tolerated with the most frequent placebo adjusted adverse events, being nausea, diarrhea, insomnia and dry mouth. Adverse events were mostly mild to moderate and transient. CONCLUSIONS: Sertraline pharmacotherapy has been demonstrated to be an effective and well-tolerated therapy for out patients with SAD. As such, sertraline offers an important pharmacological option in the clinical management of this condition.

Identification of the major glucosinolate (4-mercaptobutyl glucosinolate) in leaves of Eruca sativa L. (salad rocket).

The major and structurally unique glucosinolate (GLS) in leaves of Eruca sativa L. (salad rocket) was identified as 4-mercaptobutyl GLS. Both 4-methylthiobutyl GLS and 4-methylsulfinylbutyl GLS were also present, but at lower concentrations. The 4-mercaptobutyl GLS was observed to oxidise under common GLS extraction conditions, generating a disulfide GLS that may be reduced efficiently by tris(2-carboxyethyl) phosphine hydrochloride (TCEP) to reform the parent molecule. The identities of 4-mercaptobutyl GLS and of the corresponding dimeric GLS were confirmed by LC/MS, MS/MS and NMR. Myrosinase treatment of an enriched GLS fraction or of the purified dimer GLS generated a mixture of unique bi-functional disulfides, including bis-(4-isothiocyanatobutyl) disulfide (previously identified elsewhere). TCEP reduction of the purified dimer, followed by myrosinase treatment, yielded only 4-mercaptobutyl ITC. GLS-derived volatiles generated by autolysis of fresh seedlings and true leaves were 4-mercaptobutyl ITC (from the newly identified GLS), 4-methylthiobutyl ITC (from 4-methylthiobutyl GLS) and 4-methylsulfinylbutyl ITC (from 4-methylsulfinyl-butyl GLS); no unusual bi-functional disulfides were found in fresh leaf autolysate. These results led to the conclusion that, in planta, the new GLS must be present as 4-mercaptobutyl GLS and not as the disulfide found after extraction and sample concentration. This new GLS and its isothiocyanate are likely to contribute to the unique odour and flavour of E. sativa.

Variations in lipophilic and vacuolar flavonoids among European Pulicaria species.

Four European Pulicaria species, P. odora, P. paludosa, P. sicula and P. vulgare, were analysed for their surface and vacuolar constituents for comparison with previous data obtained for P. dysenterica. Each species had a distinct flavonoid pattern with notable differences between leaf and inflorescence. 6-Hydroxyflavonols were the major lipophilic components in all of the species and tissues except in the leaves of P. paludosa and P. vulgare, where scutellarein 6-methyl ether was the main constituent. In the leaves of P. sicula a more unusual flavone, 6-hydroxyluteolin 5,6,7,3',4'-pentamethyl ether, was a major component. Pulicaria odora was distinguished by the presence of a series of methylated 6-hydroxykaempferol derivatives including a 3,5,6,7,4'-pentamethyl ether. Quercetagetin hexamethyl ether occurred in both tissues of P. sicula together with the 3,7,3,4'-tetra methyl ether and other quercetagetin derivatives, which were 5-methylated. Quercetagetin 3,7,3'-methyl ether was present in all species except P. odora. Flavonol glucuronides were characteristic vacuolar constituents of all the taxa studied. Two rare glycosides, patuletin and 6-hydroxykaempferol 6-methyl ether 7-glucuronides were identified in the inflorescence of P. odora. Pulicaria vulgaris, a rare plant of southern England, had the vacuolar flavonoid profile most similar to the other more abundant British plant, P. dysenterica.

Seasonal affective disorder and social deprivation in Aberdeen.

BACKGROUND: Unlike non-seasonal depression, there is some evidence that seasonal affective disorder (SAD) is more common among more affluent socioeconomic groups. METHODS: In primary care settings in Aberdeen, 4557 subjects had previously completed a Seasonal Pattern Assessment Questionnaire (SPAQ). From the subjects' postcodes they were allocated a Carstairs score which placed them in one of seven categories of socioeconomic deprivation. These categories were compared with regard to seasonal pathology from the SPAQ ratings. RESULTS: Complete postcodes and Carstairs scores were established for 3772 (83%) of the 4557 subjects. No statistically significant relationship between socioeconomic deprivation and SPAQ ratings was detected. LIMITATIONS: The study population was an affluent one relative to Scotland as a whole which may have reduced the likelihood of a positive finding. The study was conducted 7 years after the census on which postcode deprivation scores were calculated, and changes therein may have occurred. CONCLUSIONS: SAD either has no relationship to social deprivation or is associated with affluence and this distinguishes it from non-seasonal depression.

A comparison of real patients, simulated patients and videotaped interview in teaching medical students about alcohol misuse.

Doctors perform poorly in identifying and in treating patients with alcohol misuse problems and this has been linked to inadequate undergraduate education. We compared three methods of teaching among Aberdeen medical students. In groups of eight or nine students, teaching was conducted with a simulated patient, with real patients or with a videotaped interview. The teachers were five consultant psychiatrists. At the end of each teaching session, students completed a measure of knowledge (multiple-choice questions), two measures of attitudes towards alcohol misusers and a questionnaire tailored to assessment of the teaching session. From the class of 176 students, 156 (89%) participated in the study. Two-way analyses of variance identified a significant difference between teaching methods; students rated the simulated patient sessions as more helpful in acquiring interview skills (F = 11.71, df 2, p < 0.001). We have since expanded our use of simulated patients in the undergraduate teaching programme.

The seasonality of bipolar affective disorder: comparison with a primary care sample using the Seasonal Pattern Assessment Questionnaire.

BACKGROUND: In contrast with recurrent unipolar depression, relatively little is known about the seasonality of depressive episodes in bipolar affective disorder (BAD). METHOD: We compared responses on the Seasonal Pattern Assessment Questionnaire (SPAQ) between a cohort of 183 patients with BAD and a large sample of patients in primary care (N=4746). Comparisons were adjusted for age and gender. RESULTS: 27% of the BAD patients fulfilled SPAQ criteria for Seasonal Affective Disorder (SAD. This gave an adjusted odds ratio of 3.73 (95% confidence intervals 2.64 to 5.27) in comparison with the rate among the primary care samples. Global seasonality scores were significantly higher among BAD patients (adjusted mean difference 1.73, 95% CI 0.97 to 2.49, p<0.001). LIMITATIONS: The SPAQ was originally designed as a screening instrument rather than as a case-finding instrument. CONCLUSIONS: Vigilance for seasonal symptom recurrence in BAD may be important with regard to management and relapse prevention.

Seasonal symptoms in bipolar and primary care patients.

BACKGROUND: There is evidence of seasonality in bipolar affective disorder (BAD) and the preponderance of atypical symptoms in bipolar depressive episodes is also seen in winter type Seasonal Affective Disorder. Differences in seasonal symptoms between BAD and appropriate comparison populations have been scrutinised only in small studies. METHODS: Symptoms described on the Seasonal Pattern Assessment Questionnaire (SPAQ) were compared between 183 patients with BAD and 468 patients consulting their general practitioners. Statistical analyses were adjusted for differing age and gender distributions between the two groups. RESULTS: Compared with the general practice patients, subjects with BAD reported greater seasonal fluctuations in mood (p=0.003). On one measure BAD subjects reported increased seasonal changes in social activity (p<0.001) and greater weight fluctuation over the year (p=0.001). The most striking differences were in sleep patterns; BAD subjects slept significantly more throughout the year, and slept for a mean of 1.8h more in winter than in summer (versus a 1.0h difference in the general practice group, p<0.001). Against 20% of the general practice group, 46% of BAD patients rated seasonal changes in well-being to be at least a moderate problem. LIMITATIONS: The SPAQ was designed as a screening instrument for Seasonal Affective Disorder, not for studies of this nature. Some of the reported differences, notably in social activity and weight changes, may reflect secondary psychosocial effects of BAD. CONCLUSIONS: Seasonal changes, most notably winter hypersomnia, should be identified in patients with BAD. These symptoms may respond to treatments such as light therapy that are used in recurrent winter depression.

High throughput screening of mutants of oat that are defective in triterpene synthesis.

The triterpenes are a large and diverse group of plant natural products that have important functions in plant protection and food quality, and a range of pharmaceutical and other applications. Like sterols, they are synthesised from mevalonate via the isoprenoid pathway, the two pathways diverging after 2,3-oxidosqualene. During triterpene synthesis 2,3-oxidosqualene is cyclised to one of a number of potential products, the most common of these being the pentacyclic triterpene beta-amyrin. Plants often produce complex mixtures of conjugated triterpene glycosides which may be derived from a single triterpene skeleton. The delineation, functional analysis and exploitation of triterpene pathways in plants therefore represent a substantial challenge. Here we have carried out high throughput screening to identify mutants of diploid oat (Avena strigosa) that are blocked in the early steps of triterpene synthesis. We also show that mutants that are affected in the first committed step in synthesis of beta-amyrin-derived triterpenes, and so are unable to cyclise 2,3-oxidosqualene to beta-amyrin (sad1 mutants), accumulate elevated levels of primary sterols. The major differences were in Delta-7-campesterol and Delta-7-avenasterol, which both increased several fold relative to wild-type levels. This is presumably due to accumulation of squalene and 2,3-oxidosqualene and consequent feedback into the sterol pathway, and is consistent with previous reports in which specific oxidosqualene cyclase inhibitors and elicitors of triterpene biosynthesis were shown to have inverse effects on the flux through the sterol and triterpene pathways.

Wake-up call for British psychiatry.

The recent drive within the UK National Health Service to improve psychosocial care for people with mental illness is both understandable and welcome: evidence-based psychological and social interventions are extremely important in managing psychiatric illness. Nevertheless, the accompanying downgrading of medical aspects of care has resulted in services that often are better suited to offering non-specific psychosocial support, rather than thorough, broad-based diagnostic assessment leading to specific treatments to optimise well-being and functioning. In part, these changes have been politically driven, but they could not have occurred without the collusion, or at least the acquiescence, of psychiatrists. This creeping devaluation of medicine disadvantages patients and is very damaging to both the standing and the understanding of psychiatry in the minds of the public, fellow professionals and the medical students who will be responsible for the specialty's future. On the 200th birthday of psychiatry, it is fitting to reconsider the specialty's core values and renew efforts to use psychiatric skills for the maximum benefit of patients.