Health service COVID-19 wellbeing and support initiatives: a mixed-methods evaluation.

BACKGROUND: Health services implemented a range of initiatives during the COVID-19 pandemic to support employee wellbeing and assist employees to manage the professional and personal challenges they experienced. However, it is not known if such initiatives were acceptable to employees or met their needs. AIMS: To evaluate the wellbeing and support initiatives implemented at an Australian health service during the COVID-19 pandemic from the perspectives of employees (both users and non-users) and key stakeholders. METHODS: A mixed-methods design (survey, interviews and data audit) to investigate employees' and key stakeholders' perceptions, experiences and use of the wellbeing and support initiatives implemented at a large tertiary metropolitan health service in Melbourne, Australia. RESULTS: Ten employees participated in an interview and 907 completed a survey. The initiatives were well used and appreciated by staff. There was no significant difference in the proportion of clinical staff who had used the initiatives compared to non-clinical staff (44% versus 39%; P=0.223). Survey respondents reported the initiatives improved their mental health (n = 223, 8%), ability to cope with COVID-19 related stress and anxiety (n = 206, 79%), do their work (n = 200, 77%) and relationships with colleagues (n = 174, 67%). Staff would like many of the initiatives (with some modifications) to continue after the COVID-19 pandemic. CONCLUSIONS: The findings suggest a high level of staff satisfaction with the implemented wellbeing and support initiatives, and confirm the need for, and importance of, developing and implementing initiatives to support health service staff during outbreaks of infectious diseases such as the COVID-19 pandemic.

Pedi-R-MAPP: The development of a nutritional awareness tool for use in remote paediatric consultations using a modified Delphi consensus.

BACKGROUND & AIMS: The Remote Malnutrition Application (R-MAPP) was developed during the COVID-19 pandemic to provide support for health care professionals (HCPs) working in the community to complete remote nutritional assessments, and provide practical guidance for nutritional care. The aim of this study was to modify the R-MAPP into a version suitable for children, Pediatric Remote Malnutrition Application (Pedi-R-MAPP), and provide a structured approach to completing a nutrition focused assessment as part of a technology enabled care service (TECS) consultation. METHODS: A ten-step process was completed: 1) permission to modify adult R-MAPP, 2) literature search to inform the Pedi-R-MAPP content, 3) Pedi-R-MAPP draft, 4) international survey of HCP practice using TECS, 5) nutrition experts invited to participate in a modified Delphi process, 6) first stakeholder meeting to agree purpose/draft of the tool, 7) round-one online survey, 8) statements with consensus removed from survey, 9) round-two online survey for statements with no consensus and 10) second stakeholder meeting with finalisation of the Pedi-R-MAPP nutrition awareness tool. RESULTS: The international survey completed by 463 HCPs, 55% paediatricians, 38% dietitians, 7% nurses/others. When HCPs were asked to look back over the last 12 months, dietitians (n = 110) reported that 5.7 ± 10.6 out of every 10 appointments were completed in person; compared to paediatricians (n = 182) who reported 7.5 ± 7.0 out of every 10 appointments to be in person (p < 0.0001), with the remainder completed as TECS consultations. Overall, 74 articles were identified and used to develop the Pedi-R-MAPP which included colour-coded advice using a traffic light system; green, amber, red and purple. Eighteen participants agreed to participate in the Delphi consensus and completed both rounds of the modified Delphi survey. Agreement was reached at the first meeting on the purpose and draft sections of the proposed tool. In round-one of the online survey, 86% (n = 89/104) of statements reached consensus, whereas in round-two 12.5% (n = 13/104) of statements reached no consensus. At the second expert meeting, contested statements were discussed until agreement was reached and the Pedi-R-MAPP could be finalised. CONCLUSION: The Pedi-R-MAPP nutrition awareness tool was developed using a modified Delphi consensus. This tool aims to support the technological transformation fast-tracked by the COVID-19 pandemic by providing a structured approach to completing a remote nutrition focused assessment, as well as identifying the frequency of follow up along with those children who may require in-person assessment.

Placental volume at 11 weeks is associated with offspring bone mass at birth and in later childhood: Findings from the Southampton Women's Survey.

OBJECTIVES: To investigate associations between placental volume (PV) at 11 weeks' gestation and offspring bone outcomes at birth, 6 years and 8 years. METHODS: 3D ultrasound scanning was used to assess 11 week PV in a subset (n = 236) of the Southampton Women's Survey (a prospective mother-offspring cohort). Maternal anthropometric measures and lifestyle information were obtained pre-pregnancy and at 11 weeks' gestation. Offspring dual-energy x-ray absorptiometry scanning was performed within 2 weeks postnatally and at 6 and 8 years. Linear regression was used to assess associations between PV and bone outcomes, adjusting for offspring age at DXA and sex, and maternal age, height, smoking status, walking speed and triceps skinfold thickness. ß are SD change in bone outcome per SD change in PV. RESULTS: In adjusted models, 11 week PV was positively associated with bone area (BA) at all time points, with evidence of persisting associations with increasing childhood age (birth: n = 80, ß = 0.23 [95%CI = 0.03, 0.42], 6 years: n = 110, ß = 0.17 [-0.01, 0.36], 8 years: n = 85, ß = 0.13 [-0.09, 0.36]). Similar associations between 11 week PV and bone mineral content (BMC) were observed. Associations with size-corrected bone mineral content were weaker at birth but strengthened in later childhood (birth: n = 78, ß = 0.07 [-0.21, 0.35], 6 years: n = 107, ß = 0.13 [-0.08, 0.34], 8 years: n = 71, ß = 0.19 [-0.05, 0.43]). CONCLUSIONS: 11 week PV is associated with DXA bone measures at birth, with evidence of persisting associations into later childhood. Further work is required to elucidate the contributions of placental morphology and function to gestational influences on skeletal development.

Health and happiness is more important than weight': a qualitative investigation of the views of parents receiving written feedback on their child's weight as part of the National Child Measurement Programme.

BACKGROUND: The present study aimed to explore parental perceptions of overweight children and associated health risks after receiving National Child Measurement Programme (NCMP) weight feedback. METHODS: Fifty-two parents of overweight and obese children aged 4-5 years and 10-11 years enrolled in the NCMP programme in England in 2010-2011 participated in qualitative, semi-structured interviews about their perceptions of their child's weight and health risk after receiving weight feedback. Interviews were audio tape recorded and were conducted either by telephone (n = 9) or in the respondents' homes (n = 41). Interviews were transcribed verbatim and analysed using interpretative thematic analysis. RESULTS: Parents who received NCMP written feedback informing them that their child was overweight disregarded the results because they viewed 'health and happiness as being more important than weight'. The feedback was viewed as less credible because it did not consider the individual child's lifestyle.'Broad definitions of healthy' were described that did not include weight,such as reference to the child having good emotional and physical health and a healthy diet. Parents attributed weight to 'inherited/acquired factors' such as genetics or puppy fat, or did not regard their child's 'appearance' as reflecting being overweight. 'Cultural influence' also meant that being overweight was not viewed negatively by some non-white parents. CONCLUSIONS: After receiving written weight feedback, parents use methods other than actual weight when evaluating their child's weight status and health risks. Parents' conceptions of health and weight should be considered when communicating with parents, with the aim of bridging the gap between parental recognition of being overweight and subsequent behaviour change.

Rapid on-site assessment of specimens by biomedical scientists improves the quality of head and neck fine needle aspiration cytology.

OBJECTIVE: Immediate rapid on-site assessment (ROSA) of fine needle aspiration cytology (FNAC) specimens by biomedical scientists (BMS), the UK equivalent of cytotechnologists, or by pathologists may improve specimen quality and cellular adequacy rates for lymph node, head and neck and thyroid FNAC. The aim of this study was to evaluate the effect of introducing ROSA by BMS in an outpatient clinic setting. METHODS: The adequacy rate and sensitivity of histological diagnosis for lymph node, thyroid and salivary gland FNAC samples were determined before and after the introduction of BMS ROSA. The additional financial costs and time required to perform this service were also estimated. RESULTS: Thirty-one patients underwent ultrasound (US)-guided FNAC with ROSA and 151 without. ROSA reduced the number of FNAC insufficient in quality for diagnosis from 43% to 19% (P = 0.0194). The estimated additional cost for pathology per patient for ROSA was between £52.05 and £70.74, equivalent to €65.40/US $83.90 and €88.89/US $114.0, respectively, an increase of between 28% and 49% from the original cost. ROSA necessitated an additional 6 minutes clinic time per patient, reducing the number of patients that could be seen in an average clinic from 13 to 10 as well as requiring increased laboratory time for FNAC slide assessment. CONCLUSION: ROSA by suitably trained biomedical scientists and with appropriate consultant pathologist support can improve the quality of FNAC sampling for head and neck lesions. Although ROSA resulted in both additional financial and time costs, these are more than likely to be offset by a reduction in patients returning to clinic for repeat FNAC or undergoing unnecessary surgery.

The impact of instrumental feeding on children's responses to taste exposure.

BACKGROUND: In a recent study, we showed that nonfood incentives combined with taste exposure increase children's acceptance of vegetables. However, the impact of children's previous experience of receiving food rewards is unknown. The present study investigated whether the experience of food rewards affects responses to an exposure-plus-reward intervention. METHODS: One hundred and thirty-seven parents of 4-6-year-old children taking part in an exposure-based intervention study completed an instrumental feeding (IF) questionnaire aiming to assess their use of food rewards. Based on these scores, children were categorised as frequently or rarely instrumentally-fed. Intervention groups were given 12 daily tastes of a target vegetable combined with no reward, a tangible reward, (sticker) or a verbal reward (praise). A no-treatment control group received no tastings. Liking and intake of a target vegetable were measured at baseline and post-intervention. RESULTS: Irrespective of experience of IF, children in all intervention groups increased liking compared to controls (all P < 0.001) and both reward groups increased intake compared to controls (both P < 0.05). However, in the nonrewarded exposure group, only children with a limited experience with food rewards increased consumption (P < 0.05). CONCLUSIONS: Experience of IF may limit the benefits of 'mere exposure'. However, exposure with nonfood rewards can increase the acceptance of vegetables, regardless of previous experience.

Environmental and individual determinants of core and non-core food and drink intake in preschool-aged children in the United Kingdom.

BACKGROUND/OBJECTIVES: Strategies to achieve healthier diets for children are likely to benefit from an understanding of the determinants. We examined environmental and individual predictors of children's intake of 'core' foods (fruit and vegetables) and 'non-core' foods (snacks and sweetened beverages). Predictors included parental intake, home availability, parental feeding styles (Encouragement and Monitoring) and children's food preferences. Based on research with older children, we expected intake of both food types to be associated with maternal intake, core foods to be more associated with children's preferences and non-core food intake more with the home environment. SUBJECTS/METHODS: Primary caregivers (n=434) of children (2-5 years) from preschools and Children's Centres in London, UK, completed a self-report survey in 2008. RESULTS: Multiple regression analyses indicated children's fruit intake was associated with maternal fruit intake (B=0.29; P=0.000), children's liking for fruit (B=0.81; P=0.000) and a Monitoring style of parental feeding (B=0.13; P=0.021). Children's vegetable intake was similarly associated with maternal intake (B=0.39; P=0.000), children's liking for vegetables (B=0.77; P=0.000), Encouragement (B=0.19; P=0.021) and Monitoring (B=0.11; P=0.029). Non-core snack intake was associated with maternal intake (B=0.25; P=0.029), Monitoring (B=-0.16; P=0.010), home availability (B=0.10; P=0.022) and television viewing (TV) (B=0.28; P=0.012). Non-core drink intake was associated with maternal intake (B=0.32; P=0.000) and TV (B=0.20; P=0.019). CONCLUSIONS: Results indicate commonalities and differences in the predictors of core and non-core food intake, with only maternal intake being important across all types. Effective interventions to improve young children's diets may need to call on different strategies for different foods.

Parental feeding behaviours and motivations. A qualitative study in mothers of UK pre-schoolers.

Parental feeding behaviours are considered major influences on children's eating behaviour. However, many questionnaire studies of feeding neglect subtle distinctions between specific feeding strategies and practices in favour of eliciting general feeding goals, and do not take account of the context provided by parents' motivations. These factors may be critical to understanding child outcomes and engaging parents in child obesity prevention. The present study obtained interview and diary data on specific feeding behaviours and underlying motivations from 22 mothers of predominantly healthy weight 3-5 y olds in the UK. Parents described a wide range of efforts to promote or restrict intake that were largely motivated by practical and health considerations and only rarely by concern about weight. There was also evidence for instrumental feeding, rules surrounding meal-time, child involvement, and parental flexibility in relation to feeding. Almost all parents described responding to children's appetitive traits, consistent with growing evidence for genetically influenced individual differences in children's appetite. These findings suggest that in order to engage parents of currently healthy weight children, obesity prevention advice should aim to satisfy their primary motivations (practicality, health), and be framed as helping parents to respond sensitively and appropriately to different children's characteristics.

The impact of flavour exposure in utero and during milk feeding on food acceptance at weaning and beyond.

An individual's experience of flavours contributes to their unique pattern of food preferences. Exposure to a specific flavour can increase familiarity and result in greater acceptance of this flavour over time. This paper describes the earliest occurrences of flavour exposure; first in utero, via amniotic fluid, and later through breast or formula milk. Evidence suggests these early experiences impact on later food preferences, but the extent to which specific flavour compounds from the mother's diet are transmitted during these pre- and early post-natal periods may vary within and between individuals. In contrast with findings with toddlers and older children, infants accept new flavours rapidly, with relatively few exposures required. Early exposure to flavour variety may improve long term dietary outcomes, highlighting the need to promote a varied diet during pregnancy and lactation.

Appetitive behaviours of children attending obesity treatment.

Associations between appetite and adiposity have not been examined in clinical samples of obese children. The Children's Eating Behaviour Questionnaire (CEBQ) was used to compare appetite in community (n=406) and clinical (n=66) samples. Clear graded patterns were seen for food responsiveness and emotional overeating; levels increased with increasing BMI SDS and the clinical sample scored highest. The reverse was seen for satiety responsiveness/slowness in eating. Differences were not solely explained by weight differences, suggesting that the clinical sample had more pronounced 'obesogenic' appetitive traits. This could make adherence to dietary guidance difficult.

Maternal perception of the causes and consequences of sibling differences in eating behaviour.

BACKGROUND/OBJECTIVES: The aim of this study is to explore mothers' perceptions of differences between their children in the eating behaviour domain. SUBJECTS/METHODS: Twelve semistructured interviews were carried out with mothers who had at least two children aged between 6 and 15 years, to discuss feeding experiences, particularly around healthy eating. Interviews were recorded and transcribed verbatim and analysed using Framework Analysis. RESULTS: Mothers frequently identified differences in appetite and food preferences between their children, which they attributed largely to genetic factors. These sibling differences meant that although feeding goals might be common, the pathways to the goals varied depending on each child's appetitive characteristics. The overall pattern was one of flexible responsiveness to each child. In contrast to perceptions of their own children's eating behaviours, feeding difficulties in other families were usually attributed to lack of parental control. CONCLUSIONS: The feeding relationship is complex and interactive, resulting in parents modulating their feeding strategies to match each child's eating behaviour. Guidance to parents on healthy feeding needs to acknowledge the nuanced and interactive nature of feeding practices.

Associations between child weight and maternal feeding styles are mediated by maternal perceptions and concerns.

OBJECTIVE: To determine whether controlling parental feeding practices are associated with children's adiposity and test the hypothesis that any associations are mediated by maternal perception of their child's weight. METHOD: Children aged 7-9 years (n=405) were weighed and measured at school as part of the Physical Exercise and Appetite in CHildren Study (PEACHES). Adiposity was indexed with body mass index s.d. scores. The Child Feeding Questionnaire was completed by 53% of mothers of participating children (n=213). Mothers reported whether they thought their child was overweight, normal weight or underweight, and rated their concern about future overweight on a 5-point scale. RESULTS: Higher child adiposity was associated with lower 'pressure to eat' and higher 'restriction' scores. Restriction increased linearly with maternal concern about overweight, and maternal concern about overweight fully mediated the association between child adiposity and restriction. Use of pressure increased as mothers perceived their child to be thinner, but perceived weight did not mediate the association between child weight status and maternal pressure to eat. Monitoring was not associated with child adiposity, maternal perception of weight or concern about overweight. CONCLUSION: Restriction appears to be a consequence of mothers' concern about their child becoming overweight rather than a cause of children's weight gain. Pressure may be a more complex response that is influenced by the desire to encourage consumption of healthy foods as well as ensure adequate energy intake and appropriate weight gain.

Natural Occurrence of Phytophthora infestans Causing Late Blight on Woody Nightshade (Solanum dulcamara) in New York.

Woody nightshade (Solanum dulcamara) is a common hedgerow herbaceous perennial in the United States, one of only three native Solanum spp. S. dulcamara is a known host of Phytophthora infestans (3), but infection is rarely reported. There is a U.S. record from Maryland (2); in 1947, Peterson (4) stated that this species had never been found blighted in its natural habitat, although in 1960 it was listed as a host of P. infestans in New York (1). The A2 mating type has not been reported on this host. On 2 July, 2009, leaf lesions similar to those of P. infestans on potato were found on wild S. dulcamara at Riverhead, NY. The plant was growing in a home garden within 10 m of potato and tomato plants infected with P. infestans. When two infected leaves of S. dulcamara were incubated for 24 h under high humidity, a pathogen growth developed around the lesion margins that was characterized by hyaline mycelium bearing lemon-shaped sporangia that released motile zoospores after chilling in water, which is consistent with P. infestans. The caducous and limoniform to ovoid sporangia were 39 to 50 µm (average 45 µm) × 26 to 28 µm (average 27 µm) with a length/breadth ratio of 1.66. No oospores were observed. Three isolates were obtained from this plant during July 2009. Growth on rye agar was indistinguishable from that of local tomato isolates of P. infestans. Detached leaflets of S. dulcamara and S. tuberosum, inoculated with the woody nightshade isolates and kept in a humid chamber, became infected and developed profuse sporulation within 5 days. The pathogen isolated was confirmed as P. infestans by morphological, biochemical, and molecular characteristics. Inoculations of attached leaves of potted S. dulcamara plants resulted in necrotic lesions with many sporangia; sporulation also developed on inoculated, attached, and detached tomato leaves. P. infestans was reisolated and identity confirmed as before. The three isolates were A2 mating type, metalaxyl-resistant, mitochondrial haplotype Ia. All were glucose-6-phosphate isomerase 100/122 and peptidase 100/100, as confirmed with single-spore isolates. RG57 fingerprint analysis confirmed that isolates from woody nightshade, tomato, and potato obtained from the same and nearby sites were identical. Although P. infestans in the United States belongs to the new population, which may infect a wider host range than the old US-1 clonal lineage, S. dulcamara infections have only been found when late blight is already widespread in neighboring fields and there is no evidence to suggest that woody nightshade acts as an overwintering host in the United States. References: (1) Anonymous. Index of Plant Diseases in the United States. Page 456 in: Agric. Handb. No. 165, 1960 (2) C. Cox. Phytopathology 38:575, 1948. (3) D. C. Erwin and O. K. Ribeiro. Page 190 in: Phytophthora Diseases Worldwide. The American Phytopathological Society, St. Paul, MN, 1996. (4) L. C. Peterson. Am. Potato J. 24:188, 1947.

Do social norms affect intended food choice?

OBJECTIVE: To evaluate the effect of social norms on intended fruit and vegetable intake. METHODS: A two-stage design to i) compare the perceived importance of normative influences vs cost and health on dietary choices, and ii) test the prediction that providing information on social norms will increase intended fruit and vegetable consumption in an experimental study. Home-based interviews (N=1083; 46% men, 54% women) were carried out as part of the Office for National Statistics Omnibus Survey in November 2008. RESULTS: The public's perception of the importance of social norms was lower (M=2.1) than the perceived importance of cost (M=2.7) or health (M=3.4) (all p's<0.001) on a scale from 1 (not at all important) to 4 (very important). In contrast, results from the experimental study showed that intentions to eat fruit and vegetables were positively influenced by normative information (p=0.011) in men but not by health or cost information; none of the interventions affected women's intentions. CONCLUSIONS: People have little awareness of the influence of social norms but normative information can have a demonstrable impact on dietary intentions. Health promotion might profit from emphasising how many people are attempting to adopt healthy lifestyles rather than how many have poor diets.

Adiposity is not associated with children's reported liking for selected foods.

It is often assumed that heightened liking for energy-dense foods contributes to the development of obesity, however previous findings on the association between adiposity and liking among common foods are inconclusive in adults and there is limited research in children. Therefore the present study assessed the association between adiposity and liking for fatty or sugary foods, fruits and vegetables in children. A community sample of children aged 7-9 years (N=366) were recruited as part of the Physical Exercise and Appetite in CHildren Study (PEACHES). Anthropometric measurements (BMI- and waist-SD scores, fat mass index) were taken alongside self-reported liking for a list of fatty or sugary foods, fruits and vegetables. Regression analyses were used to predict liking from continuous adiposity measures (BMI- and waist-SD score, fat mass index). Linear trend analysis was used to assess the patterning of liking across weight categories. Vegetables were liked less than fatty or sugary foods or fruit, but there was no difference between liking for fruit and for fatty or sugary foods. Boys had a higher liking for fatty or sugary foods than girls, although sex-by-adiposity interactions were not significant for any of the food categories. There was no association between liking for any of the food categories and adiposity. This suggests that overweight in children is not reflective of differences in liking for selected common foods. Variation in appetitive responsiveness to food with increasing adiposity may be more salient in the development of obesity.

Mothers' views on portion sizes for children.

BACKGROUND: Childhood obesity has increased steadily over recent years and has coincided with a general trend towards larger portions of foods consumed both inside and outside the home. A causal link between portion size and weight gain has not been established, although there is evidence of an association between larger portions and greater energy intake. The present study aimed to investigate parent's attitudes, knowledge, practices, and concerns about appropriate portions for children. METHODS: Four focus groups with a total of 14 volunteer mothers of 8-11-year-old children taking part in a larger school-based study. Mothers were asked their views about portion sizes for their children and were asked to demonstrate typical servings that they would offer their children, by weighing five common foods provided. Conversations were tape-recorded and transcribed for thematic analysis. RESULTS: Participants were unconcerned about portion sizes and would not welcome official guidance, particularly if it involved weighing foods. Mothers fed their children the amount that they believed they would eat and felt that this varied across children and across occasions. The weighing task revealed a wide variation in portion sizes served to children, with portions of the more energy-dense foods being smaller on average than those of less energy-dense foods. CONCLUSIONS: There was little understanding of age-appropriate serving sizes amongst mothers in this study. Education campaigns should be mindful of the need to make portion information clear and simple because parents may not be prepared to weigh the food that they serve to their children.

Patient quality of life with bone-anchored hearing aid: 10-year experience in Glasgow, Scotland.

OBJECTIVES: This study aimed to ascertain the usefulness of the bone-anchored hearing aid and its impact on the quality of life of patients fitted in Glasgow between 1996 and 2006. METHOD: The Entific Medical Systems questionnaire and the Glasgow Benefit Inventory were posted to patients in order to assess their satisfaction and quality of life changes. RESULTS: Sixty adult patients were identified, with a questionnaire response rate of 63 per cent. Thirty-two respondents (85 per cent) reported using their bone-anchored hearing aid for more than eight hours per day. Twenty-nine respondents (75 per cent) found their bone-anchored hearing aid to be generally better than their previous, conventional aid. Twenty-seven respondents (71 per cent) reported that their bone-anchored hearing aid improved their quality of life. The median total Glasgow Benefit Inventory score was +33.3. CONCLUSIONS: Bone-anchored hearing aid usage rates and satisfaction levels were high amongst patients in Glasgow. Glasgow Benefit Inventory indices were comparable to published findings from other centres. Despite this, bone-anchored hearing aid funding is still not universally available within the National Health Service in Scotland.

Changing perceptions of weight in Great Britain: comparison of two population surveys.

OBJECTIVES: To examine changes in public perceptions of overweight in Great Britain over an eight year period. DESIGN: Comparison of data on self perceived weight from population surveys in 1999 and 2007. SETTING: Household surveys of two representative samples in Great Britain. PARTICIPANTS: 853 men and 944 women in 1999, and 847 men and 989 women in 2007. MAIN OUTCOME MEASURES: Participants were asked to report their weight and height and classify their body size on a scale from "very underweight" to "obese." RESULTS: Self reported weights increased dramatically over time, but the weight at which people perceived themselves to be overweight also rose significantly. In 1999, 81% of overweight participants correctly identified themselves as overweight compared with 75% in 2007, demonstrating a decrease in sensitivity in the self diagnosis of overweight. CONCLUSIONS: Despite media and health campaigns aiming to raise awareness of healthy weight, increasing numbers of overweight people fail to recognise that their weight is a cause for concern. This makes it less likely that they will see calls for weight control as personally relevant.

NSC348884, a nucleophosmin inhibitor disrupts oligomer formation and induces apoptosis in human cancer cells.

Nucleophosmin (NPM), a multifunctional nucleolar phosphoprotein is dysregulated in human malignancies leading to anti-apoptosis and inhibition of differentiation. We evaluated the precise three-dimensional structure of NPM based on the highly conserved structure of Xenopus NO38 and its requirement to form dimers and pentamers via its N-terminal domain (residues, 1-107). We hypothesized that a small molecular inhibitor (SMI) that could disrupt the formation of dimers would inhibit aberrant NPM function(s) in cancer cells. Molecular modeling, pharmacophore design, in silico screening and interactive docking identified NSC348884 as a putative NPM SMI that disrupts a defined hydrophobic pocket required for oligomerization. NSC348884 inhibited cell proliferation at an IC(50) of 1.7-4.0 muM in distinct cancer cell lines and disrupted NPM oligomer formation by native polyacrylamide gel electrophoresis assay. Treatment of several different cancer cell types with NSC348884 upregulated p53 (increased Ser15 phosphorylation) and induced apoptosis in a dose-dependent manner that correlated with apoptotic markers: H2AX phosphorylation, poly(ADP-ribose) polymerase cleavage and Annexin V labeling. Further, NSC348884 synergized doxorubicin cytotoxicity on cancer cell viability. The data together show that NSC348884 is an SMI of NPM oligomer formation, upregulates p53, induces apoptosis and synergizes with chemotherapy. Hence, an SMI to NPM may be a useful approach to anticancer therapy.

First Report of the A2 Mating Type of Phytophthora infestans on Tomato Crops in Taiwan, Republic of China.

In a study of the Phytophthora infestans population in Taiwan, samples with symptoms typical of late blight were collected from field crops in an important potato- (Solanum tuberosum) and tomato-(Lycopersicon esculentum) production area in the central highlands region. Isolates were obtained by surface disinfecting leaf sections and plating them onto antibiotic-amended rye A agar (1). After subculturing, the pathogen was confirmed as P. infestans on the basis of morphological characters (2). Mating type was determined by co-inoculating unamended rye agar plates with mycelial plugs of the test isolate and a reference P. infestans isolate of either the A1 or A2 mating type (four plates per test isolate, two with different A1, and two with different A2 reference isolates). After incubation (15°C darkness, 7 to 14 days), plates were examined microscopically for the presence of oospores where the colonies interacted. In 2004, one isolate of 200 tested, and in 2006, one isolate of 102 tested, produced oospores only with A1 reference isolates and were concluded to be A2 mating type. In vitro testing showed the two A2 isolates were metalaxyl-resistant (ED50 values >100 mg of metalaxyl per liter on rye grain agar), which is typical of recent P. infestans isolates from potato and tomato in this area (2). Twenty-one single-sporangial isolates from each of the two A2 strains were tested for mating type against two different A1 isolates of P. infestans and confirmed as A2. These isolates were characterized using the techniques described by Deahl et al. (1) and had the allozyme genotype 100/100/111, 100/100 at the loci coding for glucose-6-phosphate isomerase and peptidase, respectively, and were mitochondrial haplotype IIb. This multi-locus genotype is characteristic of recent P. infestans isolates from tomato and potato in Taiwan, but all previous such isolates were A1 mating type and attributed to the US-11 clonal lineage (1). When evaluated on differential hosts, both A2 isolates were tomato race PH-1 and complex potato race R 0,1,2,3,4,7,9,11. RG57 fingerprinting showed that the A2 isolates had fingerprints identical to each other and to A1 P. infestans isolates of the US-11 clonal lineage from tomato in Taiwan (101 011 100 100 110 101 011 001 1). Koch's postulates were completed and the two A2 isolates were found to be highly aggressive on cultivars of potato and tomato. To our knowledge, this is the first report of A2 mating type strains of P. infestans in the field in Taiwan, but currently, their incidence is very low (<1%). One crop from which an A2 isolate was obtained also yielded an A1 isolate, while A1 isolates were obtained from crops in the vicinity of the other. The concurrent presence of the two mating types of P. infestans poses a risk of sexual reproduction and oospore formation in tomato or potato in Taiwan. References: (1) K. L. Deahl et al. Pest Manag. Sci. 58:951, 2002. (2). D. C. Erwin and O. K. Ribeiro, Page 346 in: Phytophthora Diseases Worldwide. The American Phytopathological Society. St. Paul, MN, 1996.