Incidence of fungal contamination in fresh ginseng samples and mycotoxigenic potential of representative fungal isolates.

BACKGROUND: Fresh ginseng is typically accompanied by soil after harvest, leading to contamination with harmful fungi during storage and distribution. In this study, we investigated the incidence of fungal contamination in fresh ginseng (5-6 years old) purchased from 22 different stores in Geumsan, Korea. RESULTS: The incidence of fungal contamination in the samples was 67.4-111.5%. Fusarium solani was the most abundant species in the head (38.5%) and fine root (19.3%) parts of the ginseng samples, whereas F. oxysporum was the most abundant in the main root (22.0%) part. We isolated Aspergillus, Fusarium and Penicillium spp. (total number of isolates: 395) from the ginseng samples, and 138 isolates were identified using phylogenetic analysis. Polymerase chain reaction-based screening of 65 mycotoxin-producing species revealed that two P. expansum isolates were positive for citrinin and/or patulin, and five F. oxysporum isolates were positive for fumonisin biosynthesis gene. One P. expansum isolate produced 738.0 mg kg-1 patulin, and the other produced 10.4 mg kg-1 citrinin and 12.0 mg kg-1 patulin on potato dextrose agar (PDA) medium. Among the 47 representative F. oxysporum isolates, 43 (91.5%) produced beauvericin (0.1-15.4 mg kg-1) and four of them (8.5%) produced enniatin B and enniatin B1 (0.1-1.8 mg kg-1) as well. However, none of these toxins was detected in fresh ginseng samples. CONCLUSION: Fusarium solani and F. oxysporum were the most abundant species in fresh ginseng samples. Most F. oxysporum (43) and P. expansum (2) strains isolated from fresh ginseng produced beauvericin and enniatins (B and B1), and patulin or citrinin, respectively, on PDA medium. This is the first report of the mycotoxigenic potential of P. expansum and F. oxysporum strains isolated from fresh ginseng. © 2024 Society of Chemical Industry.

Functional roles of all five putative hydrophobin genes in growth, development, and secondary metabolism in Fusarium graminearum.

Fusarium graminearum is the causal agent of Fusarium head blight in cereal crops. As in other filamentous ascomycetes, F. graminearum contains genes encoding putative hydrophobins, which are small secreted amphiphilic proteins with eight conserved cysteine residues. Here, we investigated the roles of all five hydrophobin genes (designated FgHyd1, FgHyd2, FgHyd3, FgHyd4, and FgHyd5) in various mycological traits of F. graminearum. Gene expression analyses revealed that the five FgHyd genes, all of which were under the control of G protein signaling or velvet complex proteins, were differentially expressed under various developmental conditions. Three genes (FgHyd1, FgHyd2, and FgHyd3) were constitutively expressed in all aerial structures examined (hyphae, conidia, and perithecia), and two genes (FgHyd1 and FgHyd2) were also expressed in submerged hyphae. FgHyd3 was exclusively expressed in aerial hyphae on solid surfaces, including rice grains. These genes showed markedly reduced expression in F. asiaticum, which was a closely related to F. graminearum but exhibited different mycological traits from F. graminearum. Phenotypic analyses of various gene deletion strains, including the quintuple deletion (ΔFgHyd12345) strain, confirmed that in addition to their typical functions, all five FgHyd genes were involved in other traits, such as conidiation, pathogenicity, and secondary metabolism in F. graminearum. Both RNA-seq and chemical analyses confirmed that ΔFgHyd led to overproduction of specific terpenoid compounds (e.g., trichothecenes), which has not been reported previously. Nevertheless, the lack of complete phenotypic loss of any of the traits examined, even in the ΔFgHyd12345 strain, and little cumulative action of all five FgHyd genes strongly suggest that all five hydrophobins are redundant in function and are not absolutely essential for these fungal traits in F. graminearum.

Fusarium graminearum Species Complex: A Bibliographic Analysis and Web-Accessible Database for Global Mapping of Species and Trichothecene Toxin Chemotypes.

Fusarium graminearum is ranked among the five most destructive fungal pathogens that affect agroecosystems. It causes floral diseases in small grain cereals including wheat, barley, and oats, as well as maize and rice. We conducted a systematic review of peer-reviewed studies reporting species within the F. graminearum species complex (FGSC) and created two main data tables. The first contained summarized data from the articles including bibliographic, geographic, methodological (ID methods), host of origin and species, while the second data table contains information about the described strains such as publication, isolate code(s), host/substrate, year of isolation, geographical coordinates, species and trichothecene genotype. Analyses of the bibliographic data obtained from 123 publications from 2000 to 2021 by 498 unique authors and published in 40 journals are summarized. We describe the frequency of species and chemotypes for 16,274 strains for which geographical information was available, either provided as raw data or extracted from the publications, and sampled across six continents and 32 countries. The database and interactive interface are publicly available, allowing for searches, summarization, and mapping of strains according to several criteria including article, country, host, species and trichothecene genotype. The database will be updated as new articles are published and should be useful for guiding future surveys and exploring factors associated with species distribution such as climate and land use. Authors are encouraged to submit data at the strain level to the database, which is accessible at https://fgsc.netlify.app.

Leveraging human resources for outbreak analysis: lessons from an international collaboration to support the sub-Saharan African COVID-19 response.

Emerging infectious diseases are a growing threat in sub-Saharan African countries, but the human and technical capacity to quickly respond to outbreaks remains limited. Here, we describe the experience and lessons learned from a joint project with the WHO Regional Office for Africa (WHO AFRO) to support the sub-Saharan African COVID-19 response.In June 2020, WHO AFRO contracted a number of consultants to reinforce the COVID-19 response in member states by providing actionable epidemiological analysis. Given the urgency of the situation and the magnitude of work required, we recruited a worldwide network of field experts, academics and students in the areas of public health, data science and social science to support the effort. Most analyses were performed on a merged line list of COVID-19 cases using a reverse engineering model (line listing built using data extracted from national situation reports shared by countries with the Regional Office for Africa as per the IHR (2005) obligations). The data analysis platform The Renku Project ( https://renkulab.io ) provided secure data storage and permitted collaborative coding.Over a period of 6 months, 63 contributors from 32 nations (including 17 African countries) participated in the project. A total of 45 in-depth country-specific epidemiological reports and data quality reports were prepared for 28 countries. Spatial transmission and mortality risk indices were developed for 23 countries. Text and video-based training modules were developed to integrate and mentor new members. The team also began to develop EpiGraph Hub, a web application that automates the generation of reports similar to those we created, and includes more advanced data analyses features (e.g. mathematical models, geospatial analyses) to deliver real-time, actionable results to decision-makers.Within a short period, we implemented a global collaborative approach to health data management and analyses to advance national responses to health emergencies and outbreaks. The interdisciplinary team, the hands-on training and mentoring, and the participation of local researchers were key to the success of this initiative.

Enhancing the caregiving experience of family care partners in Singapore through an arts programme for persons with dementia: an exploratory study.

Objectives: Arts-based programmes for persons with dementia have shown promise in alleviating some of the caregiving challenges for family care partners. The present study sought to broaden the sociocultural perspectives of arts-based programmes by investigating the impact of a locally developed Arts & Dementia programme for persons with dementia on their family care partners in Singapore.Methods: Thirty-two family care partners of persons with dementia who participated in the Arts & Dementia programme were recruited. A mixed-methodological study was employed utilising quantitative pre- and post-programme data from the Zarit Burden Interview and Gain in Alzheimer care Instrument, and qualitative data from semi-structured group interviews.Results: Although there were no self-reported short-term changes in perceived caregiving difficulties and gains, semi-structured group interviews revealed potential caregiving benefits. Six overarching themes were identified: (1) contentment and social engagement, (2) re-connecting and developing new interests, (3) positive influence on caregiving, (4) enhancements to the programme, (5) more arts programmes, and (6) more support for families living with dementia.Conclusion: The present study highlights potential benefits of community-based arts activities in enabling caregiving to be a more positive experience for care partners.Supplemental data for this article is available online at http://dx.doi.org/10.1080/13607863.2021.2008306'I kept blaming myself for not spending enough time with him. Communication with him is different now. Watching him on the stage, he is happy and with a purpose'. (Gary, male).

The World Health Organization's public health intelligence activities during the COVID-19 pandemic response, December 2019 to December 2021.

The coronavirus disease (COVID-19) presented a unique opportunity for the World Health Organization (WHO) to utilise public health intelligence (PHI) for pandemic response. WHO systematically captured mainly unstructured information (e.g. media articles, listservs, community-based reporting) for public health intelligence purposes. WHO used the Epidemic Intelligence from Open Sources (EIOS) system as one of the information sources for PHI. The processes and scope for PHI were adapted as the pandemic evolved and tailored to regional response needs. During the early months of the pandemic, media monitoring complemented official case and death reporting through the International Health Regulations mechanism and triggered alerts. As the pandemic evolved, PHI activities prioritised identifying epidemiological trends to supplement the information available through indicator-based surveillance reported to WHO. The PHI scope evolved over time to include vaccine introduction, emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, unusual clinical manifestations and upsurges in cases, hospitalisation and death incidences at subnational levels. Triaging the unprecedented high volume of information challenged surveillance activities but was managed by collaborative information sharing. The evolution of PHI activities using multiple sources in WHO's response to the COVID-19 pandemic illustrates the future directions in which PHI methodologies could be developed and used.

Information management practices in the WHO African Region to support response to the COVID-19 pandemic.

The rapid transmissibility of the severe acute respiratory syndrome-coronavirus-2 causing coronavirus disease-2019, requires timely dissemination of information and public health responses, with all 47 countries of the WHO African Region simultaneously facing significant risk, in contrast to the usual highly localised infectious disease outbreaks. This demanded a different approach to information management and an adaptive information strategy was implemented, focusing on data collection and management, reporting and analysis at the national and regional levels. This approach used frugal innovation, building on tools and technologies that are commonly used, and well understood; as well as developing simple, practical, highly functional and agile solutions that could be rapidly and remotely implemented, and flexible enough to be recalibrated and adapted as required. While the approach was successful in its aim of allowing the WHO Regional Office for Africa (WHO AFRO) to gather surveillance and epidemiological data, several challenges were encountered that affected timeliness and quality of data captured and reported by the member states, showing that strengthening data systems and digital capacity, and encouraging openness and data sharing are an important component of health system strengthening.

Implementing epidemic intelligence in the WHO African region for early detection and response to acute public health events.

Epidemic intelligence activities are undertaken by the WHO Regional Office for Africa to support member states in early detection and response to outbreaks to prevent the international spread of diseases. We reviewed epidemic intelligence activities conducted by the organisation from 2017 to 2020, processes used, key results and how lessons learned can be used to strengthen preparedness, early detection and rapid response to outbreaks that may constitute a public health event of international concern. A total of 415 outbreaks were detected and notified to WHO, using both indicator-based and event-based surveillance. Media monitoring contributed to the initial detection of a quarter of all events reported. The most frequent outbreaks detected were vaccine-preventable diseases, followed by food-and-water-borne diseases, vector-borne diseases and viral haemorrhagic fevers. Rapid risk assessments generated evidence and provided the basis for WHO to trigger operational processes to provide rapid support to member states to respond to outbreaks with a potential for international spread. This is crucial in assisting member states in their obligations under the International Health Regulations (IHR) (2005). Member states in the region require scaled-up support, particularly in preventing recurrent outbreaks of infectious diseases and enhancing their event-based surveillance capacities with automated tools and processes.

Evolution of structural diversity of trichothecenes, a family of toxins produced by plant pathogenic and entomopathogenic fungi.

Trichothecenes are a family of terpenoid toxins produced by multiple genera of fungi, including plant and insect pathogens. Some trichothecenes produced by the fungus Fusarium are among the mycotoxins of greatest concern to food and feed safety because of their toxicity and frequent occurrence in cereal crops, and trichothecene production contributes to pathogenesis of some Fusarium species on plants. Collectively, fungi produce over 150 trichothecene analogs: i.e., molecules that share the same core structure but differ in patterns of substituents attached to the core structure. Here, we carried out genomic, phylogenetic, gene-function, and analytical chemistry studies of strains from nine fungal genera to identify genetic variation responsible for trichothecene structural diversity and to gain insight into evolutionary processes that have contributed to the variation. The results indicate that structural diversity has resulted from gain, loss, and functional changes of trichothecene biosynthetic (TRI) genes. The results also indicate that the presence of some substituents has arisen independently in different fungi by gain of different genes with the same function. Variation in TRI gene duplication and number of TRI loci was also observed among the fungi examined, but there was no evidence that such genetic differences have contributed to trichothecene structural variation. We also inferred ancestral states of the TRI cluster and trichothecene biosynthetic pathway, and proposed scenarios for changes in trichothecene structures during divergence of TRI cluster homologs. Together, our findings provide insight into evolutionary processes responsible for structural diversification of toxins produced by pathogenic fungi.

Self-fertility in Chromocrea spinulosa is a consequence of direct repeat-mediated loss of MAT1-2, subsequent imbalance of nuclei differing in mating type, and recognition between unlike nuclei in a common cytoplasm.

The filamentous fungus Chromocrea spinulosa (Trichoderma spinulosum) exhibits both self-fertile (homothallic) and self-sterile (heterothallic) sexual reproductive behavior. Self-fertile strains produce progeny cohorts that are 50% homothallic, 50% heterothallic. Heterothallic progeny can mate only with homothallic strains, and progeny also segregate 50% homothallic, 50% heterothallic. Sequencing of the mating type (MAT) region of homothallic and heterothallic strains revealed that both carry an intact MAT1-1 locus with three MAT1-1 genes (MAT1-1-1, MAT1-1-2, MAT1-1-3), as previously described for the Sordariomycete group of filamentous fungi. Homothallic strains, however, have a second version of MAT with the MAT1-2 locus genetically linked to MAT1-1. In this version, the MAT1-1-1 open reading frame is split into a large and small fragment and the truncated ends are bordered by 115bp direct repeats (DR). The MAT1-2-1 gene and additional sequences are inserted between the repeats. To understand the mechanism whereby C. spinulosa can exhibit both homothallic and heterothallic behavior, we utilized molecular manipulation to delete one of the DRs from a homothallic strain and insert MAT1-2 into a heterothallic strain. Mating assays indicated that: i) the DRs are key to homothallic behavior, ii) looping out of MAT1-2-1 via intra-molecular homologous recombination between the DRs in self-fertile strains results in two nuclear types in an individual (one carrying both MAT1-1 and MAT1-2 and one carrying MAT1-1 only), iii) self-fertility is achieved by inter-nuclear recognition between these two nuclear types before meiosis, iv) the two types of nuclei are in unequal proportion, v) having both an intact MAT1-1-1 and MAT1-2-1 gene in a single nucleus is not sufficient for self-fertility, and vi) the large truncated MAT1-1-1 fragment is expressed. Comparisons with MAT regions of Trichoderma reesei and Trichoderma virens suggest that several crossovers between misaligned parental MAT chromosomes may have led to the MAT architecture of homothallic C. spinulosa.

Photoprotection But Not N-acetylcysteine Improves Intestinal Blood Flow and Oxidation Status in Parenterally Fed Piglets.

OBJECTIVES: The purpose of the present study was to determine if protecting parenteral nutrition solutions from ambient light and supplementing with N-acetylcysteine (NAC) improves mesenteric blood flow, gut morphology, and oxidative status of parenterally fed neonates. METHODS: Neonatal Yucatan miniature piglets (n = 23, 7-11 days old) were surgically fitted with central venous catheters and an ultrasonic blood flow probe around the superior mesenteric artery. Piglets were fed continuously for 7 days either light-protected (LP) or light-exposed (LE) complete parenteral nutrition that was enriched with either NAC or alanine (ALA). RESULTS: There were no differences in body weight or overall gut morphology among groups after 7 days. Plasma concentrations of NAC were greater and total homocysteine lower in NAC- versus ALA-supplemented pigs on day 7 (N-acetylcysteine: 94 vs 7 µmol/L; P < 0.001; homocysteine: 14 versus 21 µmol/L; P < 0.005); plasma total glutathione was not affected. Hepatic lipid peroxidation was reduced by 25% in piglets that received LP parenteral nutrition (P < 0.05). The mesenteric artery blood flow decreased in all pigs between days 2 and 6 (P < 0.001) because of parenteral feeding. Photoprotection alone (LP-ALA) attenuated the decrease in mesenteric blood flow to 66% of baseline on day 6 compared with LE-ALA (37%; P < 0.05) and LP-NAC pigs (43%; P = 0.062); LE-NAC piglets had intermediate reductions in blood flow (55%). CONCLUSIONS: Photoprotection of parenteral nutrition solutions is a simple, effective method to attenuate decline in blood flow to the gut and hepatic lipid peroxidation, which are both commonly associated with parenteral feeding.

Functional characterization of cytochrome P450 monooxygenases in the cereal head blight fungus Fusarium graminearum.

Fusarium graminearum is a prominent plant pathogenic fungus causing Fusarium head blight in major cereal crops worldwide. To understand the molecular mechanisms underlying fungal development and virulence, large collections of F. graminearum mutants have been constructed. Cytochrome P450 monooxygenases (P450s) are widely distributed in organisms and are involved in a diverse array of molecular/metabolic processes; however, no systematic functional analysis of P450s has been attempted in filamentous fungi. In this study, we constructed a genome-wide deletion mutant set covering 102 P450s and analyzed these mutants for changes in 38 phenotypic categories, including fungal development, stress responses and responses to several xenobiotics, to build a comprehensive phenotypic dataset. Most P450 mutants showing defective phenotypes were impaired in a single phenotypic trait, demonstrating that our mutant library is a good genetic resource for further fungal genetic studies. In particular, we identified novel P450s specifically involved in virulence (5) and both asexual (1) and sexual development (2). Most P450s seem to play redundant roles in the degradation of xenobiotics in F. graminearum. This study is the first phenome-based functional analysis of P450s, and it provides a valuable genetic resource for further basic and applied biological research in filamentous fungi and other plant pathogens.

The geographic distribution and complex evolutionary history of the NX-2 trichothecene chemotype from Fusarium graminearum.

Fusarium graminearum and 21 related species comprising the F. sambucinum species complex lineage 1 (FSAMSC-1) are the most important Fusarium Head Blight pathogens of cereal crops world-wide. FSAMSC-1 species typically produce type B trichothecenes. However, some F. graminearum strains were recently found to produce a novel type A trichothecene (NX-2) resulting from functional variation in the trichothecene biosynthetic enzyme Tri1. We used a PCR-RFLP assay targeting the TRI1 gene to identify the NX-2 allele among a global collection of 2515 F. graminearum. NX-2 isolates were only found in southern Canada and the northern U.S., where they were observed at low frequency (1.8%), but over a broader geographic range and set of cereal hosts than previously recognized. Phylogenetic analyses of TRI1 and adjacent genes produced gene trees that were incongruent with the history of species divergence within FSAMSC-1, indicating trans-species evolution of ancestral polymorphism. In addition, placement of NX-2 strains in the TRI1 gene tree was influenced by the accumulation of nonsynonymous substitutions associated with the evolution of the NX-2 chemotype, and a significant (P<0.001) change in selection pressure was observed along the NX-2 branch (ω=1.16) in comparison to other branches (ω=0.17) in the TRI1 phylogeny. Parameter estimates were consistent with positive selection for specific amino-acid changes during the evolution of NX-2, but direct tests of positive selection were not significant. Phylogenetic analyses of fourfold degenerate sites and intron sequences in TRI1 indicated the NX-2 chemotype had a single evolutionary origin and evolved recently from a type B ancestor. Our results indicate the NX-2 chemotype may be indigenous, and possibly endemic, to southern Canada and the northern U.S. In addition, we demonstrate that the evolution of TRI1 within FSAMSC-1 has been complex, with evidence of trans-species evolution and chemotype-specific shifts in selective constraint.

Identification of a 12-gene Fusaric Acid Biosynthetic Gene Cluster in Fusarium Species Through Comparative and Functional Genomics.

In fungi, genes involved in biosynthesis of a secondary metabolite (SM) are often located adjacent to one another in the genome and are coordinately regulated. These SM biosynthetic gene clusters typically encode enzymes, one or more transcription factors, and a transport protein. Fusaric acid is a polyketide-derived SM produced by multiple species of the fungal genus Fusarium. This SM is of concern because it is toxic to animals and, therefore, is considered a mycotoxin and may contribute to plant pathogenesis. Preliminary descriptions of the fusaric acid (FA) biosynthetic gene (FUB) cluster have been reported in two Fusarium species, the maize pathogen F. verticillioides and the rice pathogen F. fujikuroi. The cluster consisted of five genes and did not include a transcription factor or transporter gene. Here, analysis of the FUB region in F. verticillioides, F. fujikuroi, and F. oxysporum, a plant pathogen with multiple hosts, indicates the FUB cluster consists of at least 12 genes (FUB1 to FUB12). Deletion analysis confirmed that nine FUB genes, including two Zn(II)2Cys6 transcription factor genes, are required for production of wild-type levels of FA. Comparisons of FUB cluster homologs across multiple Fusarium isolates and species revealed insertion of non-FUB genes at one or two locations in some homologs. Although the ability to produce FA contributed to the phytotoxicity of F. oxysporum culture extracts, lack of production did not affect virulence of F. oxysporum on cactus or F. verticillioides on maize seedlings. These findings provide new insights into the genetic and biochemical processes required for FA production.

Sex differences and effects of prenatal exposure to excess testosterone on ventral tegmental area dopamine neurons in adult sheep.

Prenatal testosterone (T) excess in sheep results in a wide array of reproductive neuroendocrine deficits and alterations in motivated behavior. The ventral tegmental area (VTA) plays a critical role in reward and motivated behaviors and is hypothesised to be targeted by prenatal T. Here we report a sex difference in the number VTA dopamine cells in the adult sheep, with higher numbers of tyrosine hydroxylase (TH)-immunoreactive (-ir) cells in males than females. Moreover, prenatal exposure to excess T during either gestational days 30-90 or 60-90 resulted in increased numbers of VTA TH-ir cells in adult ewes compared to control females. Stereological analysis confirmed significantly greater numbers of neurons in the VTA of males and prenatal T-treated ewes, which was primarily accounted for by greater numbers of TH-ir cells. In addition, immunoreactivity for TH in the cells was denser in males and prenatal T-treated females, suggesting that sex differences and prenatal exposure to excess T affects both numbers of cells expressing TH and the protein levels within dopamine cells. Sex differences were also noted in numbers of TH-ir cells in the substantia nigra, with more cells in males than females. However, prenatal exposure to excess T did not affect numbers of TH-ir cells in the substantia nigra, suggesting that this sex difference is organised independently of prenatal actions of T. Together, these results demonstrate sex differences in the sheep VTA dopamine system which are mimicked by prenatal treatment with excess T.

An independent association of prenatal depression with wheezing and anxiety with rhinitis in infancy.

BACKGROUND: Different maternal psychological states during pregnancy have been associated with wheeze-rhinitis-eczema symptoms in children. However, previous studies were limited and it was unclear whether the type of prenatal psychological state was associated with a particular symptom. We examined the association of maternal depression and anxiety during pregnancy with wheeze-rhinitis-eczema symptoms in infancy. METHODS: In a longitudinal birth cohort (GUSTO) of 1152 mother-child pairs, wheeze-rhinitis-eczema symptoms in the infants during the first year of life were collected by parental report. Maternal depressive and anxiety symptoms were assessed at 26 weeks of gestation using the Edinburgh Postnatal Depression Scale (EPDS) and State Trait Anxiety Inventory (STAI). Logistic regression analyses were performed with adjustment for potential confounders. RESULTS: An increased risk of wheezing was found in infants of pregnant women with probable depression (EPDS ≥ 15) [odds ratio (OR) = 1.85 (95% confidence interval (CI) 1.10-3.12)], and an increased risk of rhinitis was associated with maternal anxiety [STAI state ≥ 41: OR = 1.42 (95% CI 1.04-1.93); STAI trait ≥ 43: OR = 1.38 (95% CI 1.01-1.88)]. After adjusting for known risk factors for the development of allergic disease, these associations remained significant [EPDS ≥ 15: adjusted OR = 2.09 (95% CI 1.05-4.19); STAI state ≥ 41: adjusted OR = 1.82 (95% CI 1.17-2.82); STAI trait ≥ 43: adjusted OR = 1.70 (95% CI 1.10-2.61)]. However, maternal psychological states were not associated with infantile eczema. CONCLUSION: This study suggests that there may be an independent effect of prenatal depression on wheezing and anxiety on rhinitis in infancy.

Case-control study of glucocorticoid receptor and corticotrophin-releasing hormone receptor gene variants and risk of perinatal depression.

BACKGROUND: Depression during pregnancy or after childbirth is the most frequent perinatal illness affecting women of reproductive age. It could result in unfavourable outcomes for both women and their newborns. The incidence of perinatal depression is higher for those with family history of depression and other mental illness, suggesting the contribution of genetic factors. There is postulation that disruption or fluctuation of reproductive hormones could play a part in women who are sensitive to such changes. METHODS: This is a case-control study comparing the frequencies of candidate gene variants in patients with perinatal depression with controls. Patients of Chinese descent (N = 725) were recruited from the outpatient clinics of the hospital between 2010 and 2013. Controls were patients who came for postnatal consultations at the obstetrics clinics and scored ≤ 7 on the Edinburgh Postnatal Depression Scale (EPDS) at the postnatal screening programme of the hospital. Cases with confirmed diagnosis of clinical (major) depression related to pregnancy/postpartum were recruited from the hospital's outpatient clinic. Genomic DNA was extracted from saliva samples and genotyped for the polymorphisms of interest. Differences between groups were assessed by chi-square analysis. RESULTS: CRHR1 rs242939 and rs1876828 were not polymorphic in the study population. There was no statistically significant association of perinatal depression for CRHR1 rs242941 and GR rs41423247 (BclI). When all subjects were grouped based on family history of mental illness, there was a statistically significant association of CRHR1 rs242941 with family history regardless of depression status (P = 0.043). There was also a statistically significant difference for GR rs41423247 and regularity of menstrual periods (P < 0.000). Although not statistically significant, women with perinatal depression showed a trend towards higher frequency of self-reported menstrual irregularity. CONCLUSIONS: No evidence was found for the association of any of the genetic markers with perinatal depression in this study cohort. Instead, the possible genetic links were found in women with positive family history of mental illness and menstrual irregularity, suggesting these could be identifying risk markers for women.

Treatment of primary breast tumors in de novo metastatic breast cancer.

BACKGROUND: De novo metastatic breast cancer accounts for about 3% to 6% of the more than 200,000 new breast cancer cases annually in the United States. The treatment of the primary breast tumor in these cases is a widely debated topic. Some feel that surgical resection of the breast tumor is appropriate for selected patients, whereas others recommend surgical resection only to treat or prevent uncontrolled chest wall disease. METHODS: We review the published data on treatment of the primary tumor in de novo metastatic breast cancer, including retrospective population-based and single-institution studies. We then report on the first 2 randomized controlled trials (RCTs) that evaluated the effect on survival of surgical resection of the primary breast tumor. RESULTS: Results of the published retrospective analyses are varied, but in general they associate resection with improved outcome. Early results from the first RCTs point to no survival advantage with resection of the primary tumor in this population, but important limitations of the RCTs are noted. CONCLUSIONS: The early data from RCTs do not show survival benefit from surgical resection of the primary tumor in de novo metastatic breast cancer, but these studies have some important limitations and also suggest that certain subsets may benefit. The question therefore remains unanswered, which should provide greater impetus for the completion of ongoing RCTs.

Time to pay attention: attentional performance time-stamped prefrontal cholinergic activation, diurnality, and performance.

Although the impairments in cognitive performance that result from shifting or disrupting daily rhythms have been demonstrated, the neuronal mechanisms that optimize fixed-time daily performance are poorly understood. We previously demonstrated that daily practice of a sustained attention task (SAT) evokes a diurnal activity pattern in rats. Here, we report that SAT practice at a fixed time produced practice time-stamped increases in prefrontal cholinergic neurotransmission that persisted after SAT practice was terminated and in a different environment. SAT time-stamped cholinergic activation occurred regardless of whether the SAT was practiced during the light or dark phase or in constant-light conditions. In contrast, prior daily practice of an operant schedule of reinforcement, albeit generating more rewards and lever presses per session than the SAT, neither activated the cholinergic system nor affected the animals' nocturnal activity pattern. Likewise, food-restricted animals exhibited strong food anticipatory activity (FAA) and attenuated activity during the dark phase but FAA was not associated with increases in prefrontal cholinergic activity. Removal of cholinergic neurons impaired SAT performance and facilitated the reemergence of nocturnality. Shifting SAT practice away from a fixed time resulted in significantly lower performance. In conclusion, these experiments demonstrated that fixed-time, daily practice of a task assessing attention generates a precisely practice time-stamped activation of the cortical cholinergic input system. Time-stamped cholinergic activation benefits fixed-time performance and, if practiced during the light phase, contributes to a diurnal activity pattern.