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.

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.

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.

Core undergraduate psychiatry: what do non-specialists need to know?

OBJECTIVE: The purpose of this study is to define the most relevant topics for inclusion in an undergraduate psychiatric curriculum by asking non-psychiatrists what knowledge, skills and attitudes related to psychiatry they need in their day-to-day practice. METHODS: A questionnaire study involving non-psychiatric doctors (based both in hospitals and general practice) was carried out using Delphi methodology in 2 waves. In the first wave, 408 doctors described the psychiatric competencies they required in their current posts. From this, a list of 101 psychiatric topics was generated. In the second wave, 867 doctors rated these topics according to the relevance of each topic to their practice. RESULTS: Depression, alcohol misuse and drug misuse were rated as most relevant. General practitioners found more topics relevant to their practice than did hospital doctors, and there were disparities in the relative importance that the 2 groups gave to topics. CONCLUSIONS: This study demonstrates a systematic method for developing core curricular undergraduate learning objectives in a specialty area by asking doctors outside that specialty to identify topics that are relevant to their practice. Similar methods could be used for a range of specialties other than psychiatry and could provide a rational and transparent means of developing a core curriculum for medical students, when combined with perspectives from other sources.

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.

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.

A different function for a member of an ancient and highly conserved cytochrome P450 family: from essential sterols to plant defense.

CYP51 sterol demethylases are the only cytochrome P450 enzymes with a conserved function across the animal, fungal, and plant kingdoms (in the synthesis of essential sterols). These highly conserved enzymes, which are important targets for cholesterol-lowering drugs, antifungal agents, and herbicides, are regarded as the most ancient member cytochrome P450 family. Here we present a report of a CYP51 enzyme that has acquired a different function. We show that the plant enzyme AsCYP51H10 is dispensable for synthesis of essential sterols and has been recruited for the production of antimicrobial compounds (avenacins) that confer disease resistance in oats. The AsCyp51H10 gene is synonymous with Sad2, a gene that we previously had defined by mutation as being required for avenacin synthesis. In earlier work, we showed that Sad1, the gene encoding the first committed enzyme in the avenacin pathway (beta-amyrin synthase), had arisen by duplication and divergence of a cycloartenol synthase-like gene. Together these data indicate an intimate evolutionary connection between the sterol and avenacin pathways. Sad1 and Sad2 lie within 70 kb of each other and are expressed specifically in the epidermal cells of the root tip, the site of accumulation of avenacins. These findings raise intriguing questions about the recruitment, coevolution, and regulation of the components of this specialized defense-related metabolic pathway.

YtjE from Lactococcus lactis IL1403 Is a C-S lyase with alpha, gamma-elimination activity toward methionine.

Cheese microbiota and the enzymatic conversion of methionine to volatile sulfur compounds (VSCs) are important factors in flavor formation during cheese ripening and the foci in biotechnological approaches to flavor improvement. The product of ytjE of Lactococcus lactis IL1403, suggested to be a methionine-specific aminotransferase based on genome sequence analysis, was therefore investigated for its role in methionine catabolism. The ytjE gene from Lactococcus lactis IL1403 was cloned in Escherichia coli and overexpressed and purified as a recombinant protein. When tested, the YtjE protein did not exhibit a specific methionine aminotransferase activity. Instead, YtjE exhibited C-S lyase activity and shared homology with the MalY/PatC family of enzymes involved in the degradation of L-cysteine, L-cystine, and L-cystathionine. YtjE was also shown to exhibit alpha,gamma-elimination activity toward L-methionine. In addition, gas chromatographic-mass spectrometry analysis showed that YtjE activity resulted in the formation of H2S from L-cysteine and methanethiol (and its oxidized derivatives dimethyl disulfide and dimethyl trisulfide) from L-methionine. Given their significance in cheese flavor development, VSC production by YtjE could offer an additional approach for the development of cultures with optimized aromatic properties.

Impact of pediatric epilepsy on Indian families: influence of psychopathology and seizure related variables.

The impact of epilepsy on families has been little studied in the developing countries, where it is the most common neurological disorder among children. In Vellore, India, the impact on 132 families who had a child with epilepsy was rated with the Impact of Pediatric Epilepsy on the Family Scale (IPES). An adverse impact was experienced by 42% of families. Multivariate statistical analysis revealed four factors that were significantly associated with high impact: fewer years since diagnosis (OR=0.81, 95% CI=0.71-0.93), fewer months since last seizure (OR=0.58, 95% CI=0.39-0.87), treatment with multiple antiepileptic drugs (OR=4.34, 95% CI=1.22-15.52), and increased behavior problem scores on the Child Behavior Checklist (OR=1.10, 95% CI=1.05-1.14). Factor analysis of the IPES was also conducted as a comparison with earlier findings in a developed country. We suggest that early monotherapy should be employed whenever possible and that early recognition and treatment of associated psychological problems may help to reduce the burden on families.

A case-control study of family composition in anorexia nervosa.

OBJECTIVES: The family compositions of patients with anorexia nervosa may inform consideration of the etiology of the disorder, and previous studies in this area have had methodologic weaknesses which we sought to address in a case-control design. METHODS: The family composition of 259 females with anorexia nervosa was compared with that of 200 control subjects. Birth order and numbers of brothers and sisters were compared in unmatched and matched analyses using both univariate and multivariate statistical techniques. RESULTS: In both the unpaired univariate and the matched conditional logistic regression analyses, the anorexic females were both significantly later in the birth order and had significantly fewer brothers than control subjects. DISCUSSION: Although it is possible that these findings were affected by response bias among control subjects, it is more likely that they are informative with regard to the etiology of anorexia nervosa. Possible etiologic links are discussed in relation to biologic, family, and sociocultural factors.

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.