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Facing multiple risk factors, relative to single risk factor exposure early in life can have great implications for negative child development.

Microalga Navicula sp., Spirulina platensis, and Chlorella vulgaris have the prospect of being a source of biofuel producers. Rapid cell growth, coupled with the ability to produce large lipids and less pollution, can be used as an alternative to biofuel development. Microalgae cultivation can utilize tapioca liquid waste. Addition of NaCl to regulate salinity, so optimum for microalgae growth. In addition it can reduce toxins by binding to dissolved cyanide acid present in the waste. This study aims to determine the effect of NaCl concentration on tapioca liquid waste on growth and lipid microalgae content. This study used an experimental method with a complete random factorial design. The first factor tested three species of microalgae. The second factor tested seven NaCl concentrations on tapioca liquid waste media. The results showed that the concentration of NaCl 35% in tapioca liquid waste culture media capable of producing biomass of C. vulgaris cells with the highest lipid content. The NaCl concentration capable of producing the highest microalgae biomass from the study can be developed to design more effective and efficient tapioca industrial waste treatment without damaging the environment but more productive, as a biofuel producer.

Microphytobenthic a benthic plants, found in the waters of the sunlight reaching the bottom waters. In addition to acting as a primary producer also has the potential to produce renewable biofuels The purpose of this study was to determine the microphyitobenthic abundance of river Pekacangan affected tapioca liquid industrial waste and to estimate its potential as a biofuels. This research used survey method with the sampling technique is purposive sampling based on existing environmental setting. As the main parameters are the types of microphytobenthic, while supporting research parameters are temperature, light penetration, pH, dissolved O2, BOD5, current velocity, TSS, TDS, nitrate, orthophosphate and silica. Microphytobenthic obtained at stations affected by the waste, in screening to determine its oil content.Abundance of microphytobenthic at a station directly exposed tapioca liquid waste 620 ind.mm-2.Isolated microphytobenthic River Pekacangan affected tapioca liquid waste had 22 isolates of microphytobenthos and after screened allegedly 7 isolates potential as a biofuel, namely Navicula sp., Amphora libyca, Ulothrix sp., Anabaena sp., Planctonema sp., Cymbella sp., and Eunotia sp.

Penjalin Reservoir is located in Brebes Regency, Indonesia. Human activity around Penjalin Reservoir, such as irrigation, aquaculture, and sanitation can affect its water’s quality. Plankton can be used as bioindicator since its existence is heavily affected by water physical and chemical factors. Polluted waters can affect diversity and abundance of plankton. The purpose of this research were to determine waters quality of Penjalin Reservoir, to know plankton community structure (abundance, diversity, and domination), and pollution level of each sampling station based on plankton diversity. This research used survey method on 6 sampling stations covering inlet, middle of reservoir, and outlet with 3 replicates and 4 weeks interval. Water quality were analyzed descriptively based on criteria of PP No. 82 Tahun 2001. Abundance and diversity were estimated as Shanon-Wiener index. Domination were estimated as Simpson index. Plankton abundance values varies from 4,970.30 to 12,923.37 ind/l with the most abundant species was Tetraedon minimum. Diversity index (H’) were high with value around 3.28–3.55 and domination index were around 0.04–0.07. These diversity indexes showed that the water quality of Penjalin Reservoir were not polluted.

Silica is an element that is useful to the organism especially Diatoms (Chrysophyta: Bacillariophyceae). The sources of Silica in waters derive from weathering rock-containing silica. Diatoms are a phytoplankton that able to live as a phytobenthos distributed globally in all types of waters. The purpose of this study was to determine; the silica content, the abundance of diatoms, and the relationship between the content of silica and the abundance of diatoms in the Pelus River Banyumas. This research was conducted as a survey and samples were collected using composite sampling technique at 5 stations. Samples were collected three times with 2 weeks intervals. Two main parameters (diatoms abundance and silica content) and ten supporting parameters (temperature, current velocity, pH, DO, BOD, COD, TSS, TDS, nitrate, and ortofosfat of waters) were measured. Data of analysis calculated in this study including regression correlation analysis to determine the relationship of the silica content and the abundance of diatoms. The silica concentration in the Pelus River waters varies between 112.48-175.00 mg.l-1 with an average of 146 mg.l-1. The total abundance of benthic diatoms was 44,442 ind.cm-2. The highest diatoms abundance was at station II (11,128 ind.cm-2), the lowest was at Station IV (6,828 ind.cm-2). The relationship between silica contained in the waters and abundance of diatoms indicated by the value of R2 (coefficient of determination) by 0.38 or 38%. The abundance of Diatoms are affected 62% by the available silica in the environment, and the rest 38% e rest are determined by other factors.

Nitrogen (N) and phosphorus (P) affect the growth of phytoplankton in the waters. Nitrogen is an important part in forming protein in organisms, while phosphorus is the most essential element for growth and contributes in protein formation and cell metabolism in organisms. The activities from the catchment area that enter into the P.B Soedirman Reservoir can affect both concentration of N and P. The comparison total nitrogen (TN) and total phosphorus (TP) is the limiting factor to affect the growth of phytoplankton. Chrysophyta is one of division from phytoplankton that has function as an important component in the food chain and become as natural feed for fish. This research showed the abundance of Chrysophyta, relations of TN with the abundance of Chrysophyta; TP with the abundance of Chrysophyta; TN/TP with the abundance of Chrysophyta; TN, TP, TN/TP with the abundance Chrysophyta in the P.B Soedirman Reservoir, Banjarnegara Regency. This research used survey method with purposive sampling technique on 7 observation stations with 3 repeating. The relation of TN/TP with the abundance of Chrysophyta were analyzed used correlation regression - correlation analyzis. The results of the research showed that total abundance Chrysophyta was between 339-9570 ind/l, relation between TN/TP with the abundance of Chrysophyta with the degree was weak to very strong correlation. The most affection correlation was shown by of TN, TP, TN/TP collectively with the abundance of Chrysophyta with coefficient value (r) of 0,890 with the strength of the relation of 79,3%. The regression analysis of TN, TP, TN/TP collectively with the abundance of Chrysophyta was shown by the equation Y= – 80987,801 – 8499,931TN + 1,684TP + 406,373TN/TP.

Background: Despite an overall poor prognosis, about 15% of patients with advanced-stage tubo-ovarian high-grade serous carcinoma (HGSC) survive ten or more years after standard treatment., Methods: We evaluated the tumor microenvironment of this exceptional, understudied group using a large international cohort enriched for long-term survivors (LTS; 10+ years; n = 374) compared to medium-term (MTS; 5-7.99 years; n = 433) and short-term survivors (STS; 2-4.99 years; n = 416). Primary tumor samples were immunostained and scored for intra-epithelial and intra-stromal densities of 10 immune-cell subsets (including T cells, B cells, plasma cells, myeloid cells, PD-1+ cells, and PD-L1+ cells) and epithelial content., Results: Positive associations with LTS compared to STS were seen for 9/10 immune-cell subsets. In particular, the combination of intra-epithelial CD8+ T cells and intra-stromal B cells showed near five-fold increased odds of LTS compared to STS. All of these associations were stronger in tumors with high epithelial content and/or the C4/Differentiated molecular subtype, despite immune-cell densities generally being higher in tumors with low epithelial content and/or the C2/Immunoreactive molecular subtype., Conclusions: The tumor microenvironment of HGSC long-term survivors is distinguished by the intersection of T and B cell co-infiltration, high epithelial content and C4/Differentiated molecular subtype, features which may inspire new approaches to immunotherapy., Funding: Ovarian Cancer Research Program (OCRP) of the Congressionally Directed Medical Research Program (CDMRP), U.S. Department of Defense (DOD); American Cancer Society; BC Cancer Foundation; Canada's Networks of Centres of Excellence; Canadian Cancer Society; Canadian Institutes of Health Research; Cancer Councils of New South Wales, Victoria, Queensland, South Australia and Tasmania, Cancer Foundation of Western Australia; Cancer Institute NSW; Cancer Research UK; Deutsche Forschungsgesellschaft; ELAN Funds of the University of Erlangen-Nuremberg; Fred C. and Katherine B. Andersen Foundation; Genome BC; German Cancer Research Center; German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research; Instituto de Salud Carlos III; Mayo Foundation; Minnesota Ovarian Cancer Alliance; Ministerio de Economía y Competitividad; MRC; National Center for Advancing Translational Sciences; National Health and Medical Research Council of Australia (NHMRC); Ovarian Cancer Australia; Peter MacCallum Foundation; Sydney West Translational Cancer Research Centre; Terry Fox Research Institute; The Eve Appeal (The Oak Foundation); UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge; University of Pittsburgh School of Medicine; U.S. National Cancer Institute of the National Institutes of Health; VGH & UBC Hospital Foundation; Victorian Cancer Agency.

Background: Attachment quality may affect psychological functioning. However, evidence on attachment representations and their correlates in children born to parents with schizophrenia and bipolar disorder is sparse., Methods: We compared attachment representations in a Danish sample of 482 children aged 7 years at familial high risk of schizophrenia, bipolar disorder, and population-based controls and examined associations between attachment and mental disorders and daily functioning. Attachment representations were examined with the Story Stem Assessment Profile (SSAP). Mental disorders were ascertained in diagnostic interviews. Daily functioning was assessed with the Children's Global Assessment Scale., Results: We found no between-group differences in attachment. Higher levels of secure attachment were associated with decreased risk of concurrent mental disorders in the schizophrenia high-risk group. Higher levels of insecure and disorganized attachment were associated with increased risk of mental disorders across the cohort. Higher levels of secure and insecure attachment were associated with better and poorer daily functioning, respectively. In the current study, results regarding defensive avoidance could not be reported due to methodological limitations., Conclusion: Familial high risk of schizophrenia (FHR-SZ) or bipolar disorder is not associated with less secure or more insecure attachment at age 7. Insecure and disorganized attachment representations index risk of mental disorders and poorer functioning. Secure attachment may be a protective factor against mental disorders in children at FHR-SZ. Validation of the SSAP is needed., (© 2023 Scandinavian Psychological Associations and John Wiley & Sons Ltd.)

Background: Dysregulation of the HPA-axis, perceived stress and interpersonal trauma are associated with an elevated risk for schizophrenia and bipolar disorder. Being at familial high-risk of these two mental disorders also constitutes an increased risk. In this study, we aimed to investigate hair cortisol concentrations and perceived stress among 7-year-old children at familial high-risk of schizophrenia (FHR-SZ), bipolar disorder (FHR-BP), and population-based controls (controls)., Methods: A total of 515 children (mean age 7.8, SD 0.2) from baseline assessment of the Danish High Risk and Resilience Study - VIA 7 participated in this study. Hair cortisol concentrations were analyzed among 322 children (FHR-SZ; N = 111, FHR-BP; N = 82, controls; N = 129). Perceived stress was assessed with the Daily Life Stressor Scale including 512 children (FHR-SZ; N = 195, FHR-BP; N = 118, controls; N = 199). Interpersonal trauma was measured with face-to-face interviews., Results: Seven-year-old children at FHR-SZ or FHR-BP did not have a higher level of hair cortisol concentrations compared with controls (FHR-SZ: mean: 5.10, 95%CI 3.69-6.52; FHR-BP: mean: 5.01, 95%CI 3.27-6.72; controls: mean: 4.51, 95%CI 3.61-5.40; p = 0.77). Self-reported perceived stress was higher among children at FHR-SZ and FHR-BP compared with controls (FHR-SZ: mean: 12.09, 95%CI 10.99-13.19; FHR-BP: mean: 10.69, 95%CI 9.38-11.99; controls: mean: 8.90, 95%CI 8.13-9.68; p < 0.001). There was no significant association between hair cortisol concentrations and perceived stress (p = 0.84). Exploratory analyses revealed that interpersonal trauma exposure was neither associated with elevated hair cortisol nor perceived stress., Conclusions: Children at FHR-SZ and FHR-BP did not exhibit higher levels of hair cortisol concentrations at age 7, while both FHR-groups had higher level of self-reported perceived stress compared with controls. Early attention to stress in children at FHR is crucial and these vulnerabilities should be targeted in future interventions studies., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Scientific uncertainty during pandemic outbreaks poses a challenge for health communicators. Debates continue over the extent to which health officials should be transparent about uncertainty and the extent to which they should suppress uncertainty and risk losing the public's trust when information changes. The middle ground, the concept of "reasoned transparency," proposes that communicators focus on interpreting uncertainty to the public in ways informed by risk research. However, little guidance exists for health officials on how to do so in this context. After conducting a series of one-to-one interviews about people's coronavirus disease 2019 information habits, we identified significant trends in the heuristics that people depended on to process uncertainty. Based on those trends, we propose health communicators use narratives of science as evolving to set expectations for change, and that when changes do occur, health communicators note divergences from the past and avoid simply replacing old information with new information.

Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC., (© 2023 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Background: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC., Methods: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated., Results: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss., Conclusion: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC., (© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Objective: Mucinous ovarian carcinoma (MOC) is a rare histotype of ovarian cancer, with low response rates to standard chemotherapy, and very poor survival for patients diagnosed at advanced stage. There is a limited understanding of the MOC immune landscape, and consequently whether immune checkpoint inhibitors could be considered for a subset of patients., Methods: We performed multicolor immunohistochemistry (IHC) and immunofluorescence (IF) on tissue microarrays in a cohort of 126 MOC patients. Cell densities were calculated in the epithelial and stromal components for tumor-associated macrophages (CD68+/PD-L1+, CD68+/PD-L1-), T cells (CD3+/CD8-, CD3+/CD8+), putative T-regulatory cells (Tregs, FOXP3+), B cells (CD20+/CD79A+), plasma cells (CD20-/CD79a+), and PD-L1+ and PD-1+ cells, and compared these values with clinical factors. Univariate and multivariable Cox Proportional Hazards assessed overall survival. Unsupervised k-means clustering identified patient subsets with common patterns of immune cell infiltration., Results: Mean densities of PD1+ cells, PD-L1- macrophages, CD4+ and CD8+ T cells, and FOXP3+ Tregs were higher in the stroma compared to the epithelium. Tumors from advanced (Stage III/IV) MOC had greater epithelial infiltration of PD-L1- macrophages, and fewer PD-L1+ macrophages compared with Stage I/II cancers (p = 0.004 and p = 0.014 respectively). Patients with high epithelial density of FOXP3+ cells, CD8+/FOXP3+ cells, or PD-L1- macrophages, had poorer survival, and high epithelial CD79a + plasma cells conferred better survival, all upon univariate analysis only. Clustering showed that most MOC (86%) had an immune depleted (cold) phenotype, with only a small proportion (11/76,14%) considered immune inflamed (hot) based on T cell and PD-L1 infiltrates., Conclusion: In summary, MOCs are mostly immunogenically 'cold', suggesting they may have limited response to current immunotherapies., Competing Interests: Declaration of Competing Interest NSM has received a travel grant from NanoString technologies, unrelated to this work. DDLB has received research support grants from Roche-Genentech, AstraZeneca, and BeiGene (paid to institution); and personal consulting fees from Exo Therapeutics, that are outside the submitted work. MF has participated in Advisory Boards/Consulting from Astra Zeneca, Novartis, GSK, Takeda, Lilly, MSD Eisei and received honoraria/speakers' fees from AstraZeneca, GSK, ACT-Genomics; Research funding to institution: from AstraZeneca, Novartis, Beigene, all unrelated to this work. ADeF has received funding from AstraZeneca, unrelated this work. NS has received honoraria for invited participation in advisory boards hosted by Astra-Zeneca-MSD and Glaxo SmithKline, unrelated to this work. UM had stock ownership in Abcodia until October 2021, and UCL had a license agreement (2011–2021) with Abcodia not related to this work. BHN is a co-founder of Innovakine Therapeutics Inc., unrelated to this work., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Knowledge about representativity of familial high-risk studies of schizophrenia and bipolar disorder is essential to generalize study conclusions. The Danish High Risk and Resilience Study (VIA 7), a population-based case-control familial high-risk study, creates a unique opportunity for combining assessment and register data to examine cohort representativity., Methods: Through national registers, we identified the population of 11,959 children of parents with schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) and controls from which the 522 children participating in The VIA 7 Study (202 FHR-SZ, 120 FHR-BP and 200 controls) were selected. Socio-economic and health data were obtained to compare high-risk groups and controls, and participants versus non-participants. Selection bias impact on results was analyzed through inverse probability weights., Results: In the total sample of 11,959 children, FHR-SZ and FHR-BP children had more socio-economic and health disadvantages than controls (p < 0.001 for most). VIA 7 non-participants had a poorer function, e.g. more paternal somatic and mental illness (p = 0.02 and p = 0.04 for FHR-SZ), notifications of concern (FHR-BP and PBC p < 0.001), placements out of home (p = 0.03 for FHR-SZ), and lower level of education (p ≤ 0.01 for maternal FHR-SZ and FHR-BP, p = 0.001 for paternal FHR-BP). Inverse probability weighted analyses of results generated from the VIA Study showed minor changes in study findings after adjustment for the found selection bias., Conclusions: Familial high-risk families have multiple socio-economic and health disadvantages. In The VIA 7 Study, although comparable regarding mental illness severity after their child's birth, socioeconomic and health disadvantages are more profound amongst non-participants than amongst participants., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Recently, we showed a >60% difference in 5-year survival for patients with tubo-ovarian high-grade serous carcinoma (HGSC) when stratified by a 101-gene mRNA expression prognostic signature. Given the varied patient outcomes, this study aimed to translate prognostic mRNA markers into protein expression assays by immunohistochemistry and validate their survival association in HGSC., Methods: Two prognostic genes, FOXJ1 and GMNN, were selected based on high-quality antibodies, correlation with protein expression and variation in immunohistochemical scores in a preliminary cohort (n = 134 and n = 80, respectively). Six thousand four hundred and thirty-four (FOXJ1) and 5470 (GMNN) formalin-fixed, paraffin-embedded ovarian neoplasms (4634 and 4185 HGSC, respectively) represented on tissue microarrays from the Ovarian Tumor Tissue Analysis consortium underwent immunohistochemical staining and scoring, then univariate and multivariate survival analysis., Results: Consistent with mRNA, FOXJ1 protein expression exhibited a linear, increasing association with improved overall survival in HGSC patients. Women with >50% expression had the most favourable outcomes (HR = 0.78, 95% CI 0.67-0.91, p < 0.0001). GMNN protein expression was not significantly associated with overall HSGC patient survival. However, HGSCs with >35% GMNN expression showed a trend for better outcomes, though this was not significant., Conclusion: We provide foundational evidence for the prognostic value of FOXJ1 in HGSC, validating the prior mRNA-based prognostic association by immunohistochemistry., (© 2022. The Author(s).)

Asia has become the epicentre of type 2 diabetes (T2D), predominately due to the consumption of carbohydrate-rich and high-glycemic-index (high-GI) diets. Previously, almond consumption has been reported to reduce the risk of T2D, obesity, and related diseases. The hypothesis of this randomised cross-over clinical trial was that almond paste consumption with bread would improve postprandial glycemic and insulinemic responses. Fifteen healthy Chinese men consumed four bread-based meals containing different amounts of almond paste and inulin. Our results show that co-ingesting bread with 15 g of almond paste and 4 g of inulin significantly reduced the postprandial glucose and insulin levels. The corresponding GI value was 44 (low GI), which was lower than the GI value of white bread, which was 60 (medium GI). However, co-ingestion of almond paste with bread increased the postprandial triglyceride levels. Further studies will be required to demonstrate these effects on a long term basis. Clinical trial registration No: NCT05504044.

Objectives: Emotion regulation is a predictor of overall life outcome. Problems of emotion regulation are associated with multiple psychiatric disorders and could be a potential treatment target for improving well-being and functioning. Children at familial high risk of severe mental illness have a markedly increased risk of various psychopathology and constitute a group at significant risk of emotion regulation problems. Investigations of emotion regulation in children at familial high risk of severe mental illness are sparse., Methods: We applied an instrument for assessing emotion regulation, the Tangram Emotion Coding Manual (TEC-M), to a population-based cohort of 522 7-year-old children born to parents diagnosed with either schizophrenia or bipolar disorder and matched controls. The TEC-M is an ecologically valid, clinician-rated observational test measure of spontaneous emotion regulation. We aimed to compare emotion regulation between risk groups and to investigate associations between emotion regulation and psychopathology and daily life functioning, and between emotion regulation and an acknowledged questionnaire-based dysregulation profile., Results: In this early developmental phase, we found no between group differences in emotion regulation. We found a significant but weak negative association between emotion regulation and both child psychopathology and the presence of a dysregulation profile on the Child Behavior Checklist and a weak positive association between emotion regulation and current level of functioning., Conclusions: These findings contribute to the understanding of emotion regulation in familial high-risk children and further studies of emotion regulation in children at familial high risk of severe mental illness are warranted., (© 2022 British Psychological Society.)

This article examines how imagined audiences and impression management strategies shape COVID-19 health information sharing practices on social media and considers the implications of this for combatting the spread of misinformation online. In an interview study with 27 Canadian adults, participants were shown two infographics about masks and vaccines produced by the World Health Organization (WHO) and asked whether or not they would share these on social media. We find that interviewees' willingness to share the WHO infographics is negotiated against their mental perception of the online audience, which is conceptualized in three distinct ways. First, interviewees who would not share the infographics frequently describe a self-similar audience of peers that are "in the know" about COVID-19; second, those who might share the infographics conjure a specific and contextual audience who "needs" the information; and finally, those who said they would share the infographics most frequently conjure an abstract audience of "the public" or "my community" to explain that decision. Implications of these sharing behaviors for combatting the spread of misinformation are discussed., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Carotenoids, tocopherols and phylloquinone are highly valued in vegetables due to their potential health benefits. The profile of eight carotenoids, four tocopherols, and phylloquinone in 26 green leafy vegetables (GLV) commonly consumed in Southeast Asia were analysed by high-performance liquid chromatography with atmospheric pressure chemical ionisation and tandem mass spectrometry (HPLC-APCI-MS/MS). Lutein, β-carotene and α-tocopherol were the predominant carotenoids and tocopherol in the GLV. Among 26 GLV, sweet leaf bush contained the highest amount of total carotenoids (494 ± 22 µg/g fresh weight (FW)), tocopherols (214 ± 60 µg/g FW) and phylloquinone (18 ± 2 µg/g FW). Other underutilised GLV, including wolfberry leaves, cassava leaves and moringa leaves, are also a rich source of fat-soluble micronutrients. Overall, this study enhanced the understanding of micronutrient composition in underutilised GLV in Southeast Asia. Data will be important for diet recommendations to promote the nutritional status of the population in the region., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Children born to parents with severe mental illness are at increased risk of mental and behavioral difficulties during childhood. We aimed to investigate the occurrence of clinically significant behavioral difficulties in 7-year-old children of parents diagnosed with schizophrenia or bipolar disorder as well as in control children by using the Strengths and Difficulties Questionnaire (SDQ). Further, we aimed to determine if the SDQ could function as a screening instrument for clinically relevant behavioral problems of children at high risk of these severe mental illnesses., Methods: By means of the Danish National Registers, we established a cohort of 522 7-year old children stratified by familial high risk for schizophrenia spectrum disorder ( N = 202), bipolar disorder ( N =120), and controls ( N = 200). The child's primary caregiver completed the SDQ parent version and the Child Behavior Checklist (CBCL) while the schoolteacher completed the SDQ teacher version and the CBCL teacher equivalent; the Teachers Report Form (TRF). Finally, global functioning was assessed with the Children's Global Assessment Scale (CGAS)., Results: Children with familial high risk of schizophrenia spectrum disorder or bipolar disorder have a significantly increased risk (OR = 3.8 and 2.3) of suffering clinically significant behavioral difficulties at age 7-years according to SDQ parent ratings. The SDQ discriminates with moderate to high sensitivity and high specificity between familial high-risk children with and without a psychiatric diagnosis and has overall compelling discriminatory abilities in line with the more time consuming CBCL/TRF.Conclusions Familial high-risk children have more behavioral difficulties and more frequently at a level indicative of mental illness compared to control children as measured by the SDQ. The SDQ works well as a screening instrument for clinically relevant behavioral problems in high-risk children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Spang, Thorup, Ellersgaard, Hemager, Christiani, Burton, Gantriis, Greve, Gregersen, Mors, Nordentoft, Jepsen, Obel and Plessen.)

Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N = 2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N = 522 HGSC) and compared with Ki-67. Kaplan-Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naïve HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR = 0.87, 95% CI 0.81-0.92, p < 0.0001, N = 1840) in multivariable analysis. MCM3 mRNA expression was highest in the HGSC C5.PRO molecular subtype, although no interaction was observed between MCM3, survival and molecular subtypes. MCM3 and Ki-67 protein levels were significantly lower after exposure to neoadjuvant chemotherapy compared to chemotherapy-naïve tumors: 37.0% versus 46.4% and 22.9% versus 34.2%, respectively. Among chemotherapy-naïve HGSC, high MCM3 protein levels were also associated with significantly longer disease-specific survival (HR = 0.52, 95% CI 0.36-0.74, p = 0.0003, N = 392) compared to cases with low MCM3 protein levels in multivariable analysis. MCM3 immunohistochemistry is a promising surrogate marker of proliferation in HGSC., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Children with familial high-risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) are frequently affected in a range of domains known to be precursors of severe mental illness. No previous studies have gathered known precursors to examine whether they distribute evenly across familial high risk (FHR) children or if they cluster among a smaller group. Since such examination holds the potential to identify high and low risk of severe mental illness groups, we aimed to cluster FHR and control children affected to various degrees., Method: In The Danish High Risk and Resilience Study VIA 7, a clinical cohort study, 514 7-year-old children with FHR-SZ or FHR-BP and matched controls were assessed in domains of motor function, neurocognition, emotional control, behavior, social cognition, self-perception, language, psychotic experiences, and psychopathology, and grouped using cluster analysis. Associations between clusters and parents' level of education, functioning, caregiver status, child's level of stimulation and support in the home, and polygenic risk scores were examined., Results: A total of four groups including one of broadly affected children were identified. The broadly affected group was represented 4-5-fold (18.1%) amongst FHR-SZ children and 2-3-fold (10.2%) amongst FHR-BP children, compared to controls (4.1%) ( P < .001), and the broadly affected group had lower levels of caregiver functioning ( P < .001) and stimulation and support at home ( P < .001)., Conclusion: Precursors of severe mental illness distribute unevenly among FHR children; while approximately half are not affected in any domains, the other half are affected to various degrees. Targeted support towards the affected groups is indicated., (© The Author(s) 2022. Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.)

Background: Slower and suboptimal decision making has been identified in adults with schizophrenia and bipolar disorder. Owing to the limited evidence on decision making in first-degree relatives, we aimed to investigate, whether alterations in decision making are present in young children at familial high risk of bipolar disorder or schizophrenia., Methods: In this population-based cohort study we assessed decision making in 197 children at familial high risk of schizophrenia (FHR-SZ), 115 children at familial high risk of bipolar disorder (FHR-BP), and 190 controls aged seven using the Cambridge Gambling Task. Potential associations to neurocognition, psychopathology, and the home environment were investigated., Results: Children at FHR-SZ or FHR-BP displayed intact decision making. Quality of decision making showed significant but weak cross-sectional associations to neurocognition and adequacy of the home environment. Associations to aspects of executive functions and the home environment differed across groups., Limitations: Due to the cross-sectional nature of this study, the predictive value of efficient and inefficient decision making remains to be investigated in planned follow-up studies of this cohort., Conclusions: Young children at FHR-SZ or FHR-BP do not differ from controls in decision making efficacy, which does not appear to be an early risk marker of bipolar disorder or schizophrenia. Decision making is weakly associated to neurocognition and the home environment, but not to general intelligence or psychopathology., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We aimed to examine the prevalence of psychotic experiences (PEs) in children with familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) and, in exploratory analyses, to examine the possible associations between PEs and mental disorders as well as level of functioning. A cohort of seven-year-old children with FHR-SZ (N = 199), FHR-BP (N = 118) and controls (N = 196) was recruited through Danish nationwide registers. Lifetime PEs were assessed through interviews using the psychosis section of the 'Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime Version' (K-SADS-PL). Lifetime DSM-IV diagnoses were ascertained through K-SADS-PL and the level of functioning of the children through 'Children's Global Assessment Scale'. Both children with FHR-SZ (OR = 2.9, 95% CI = 1.4-6.2, p = 0.005) and FHR-BP (OR = 2.9, 95% CI = 1.3-6.7, p = 0.011) had an increased risk of having experienced "severe" PEs compared with controls. In the overall cohort PEs were associated with any lifetime mental disorder, Attention-Deficit/Hyperactivity Disorder, anxiety disorders and a lower level of functioning. The findings of a higher proportion of high risk children reporting PEs could represent an early manifestation of later more severe psychopathology or simply an unspecific transitory symptom. Future follow-up studies of this cohort will explore the predictive value of the occurrence of PEs at age seven., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Background: Children with familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) are at increased risk of developing similar disorders and show cognitive deficits during childhood. The aim of this paper is to investigate visual attention and its developmental trajectories in children with FHR-SZ and with FHR-BP to increase our knowledge about potential cognitive endophenotypes of these two disorders., Methods: We compared the performance of 89 children with FHR-SZ (N = 32), FHR-BP (N = 22), and population-based controls (PBC, N = 35) at age 7 to that at age 12 as well as including 133 12-year-old children with FHR-SZ (N = 50), FHR-BP (N = 43) and PBC (N = 40) to investigate visual attention, as part of the Danish High Risk and Resilience Study. We used the TVA-based whole report paradigm, based on the Bundesen's Theory of Visual Attention (TVA) to investigate visual attention., Results: Children with FHR-SZ that showed deficits in visual processing speed at age 7 improved to a level that was not significantly different from controls at age 12. All children improved over time. We found no attentional deficits in FHR children at age 12., Conclusions: On visual attention, children with FHR-SZ did not show developmental deficits or lags and, together with children with FHR-BP, they develop similarly to control children between age 7 to age 12. This emphasizes the potential of beneficial neuroplastic changes in cognitive deficits found at younger ages in children with FHR-SZ. It also highlights the importance of identifying and characterizing cognitive developmental trajectories of high-risk children and provides hope that visual attention may develop appropriately in these groups., Competing Interests: Declaration of competing interest HRS has received honoraria as speaker from Sanofi Genzyme, Denmark and Novartis, Denmark, as consultant from Sanofi Genzyme, Denmark and as senior editor (NeuroImage) and editor-in-chief (Neuroimage Clinical) from Elsevier Publishers, Amsterdam, The Netherlands. HRS has also received royalties as book editor from Springer Publishers, Stuttgart, Germany and Gyldendahl Publishers, Copenhagen, Denmark., (Copyright © 2021 Elsevier B.V. All rights reserved.)

It is well established that children with familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) have a higher risk of developing mental disorders, however, little is known of to what degree the genetic and environmental vulnerabilities affect the quality of life and self-esteem of these children. We aimed to compare the quality of life and self-esteem between children with FHR-SZ or FHR-BP and controls. We used Danish nationwide registers to retrieve a cohort of 522 7-year-old children with FHR-SZ or FHR-BP and controls. Quality of life was assessed with the 'Health-related Quality of Life Screening Instrument', KIDSCREEN-27, and the scale 'Social Acceptance (Bullying)' from the KIDSCREEN-52. Self-esteem was assessed with the self-report scale 'I think I am'. Assessors were blind to familial risk status of the children. Children with FHR-SZ displayed lower levels of the general quality of life, as well as lower scores on the 'Psychological Well-being' scale and the 'School Environment' scale of the KIDSCREEN-27 compared with controls. Both children with FHR-SZ and FHR-BP reported more bullying victimization compared with controls. Children with FHR-SZ reported lower self-esteem on the total scale of 'I think I am', as well as on the 'Skills and talents', the 'Psychological well-being', and the 'Relationships with others' subscales compared with controls. The findings of lower quality of life and self-esteem in children with FHR-SZ together with more bullying victimization in both familial high-risk groups call for studies on low risk, early intervention strategies towards this group of vulnerable children.

Wheat noodles are a staple commonly consumed in Asia, but high intakes have been associated with type 2 diabetes due to its rapid starch digestibility. We hypothesised that protein network-binding via transglutaminase (TG) would form a stronger barrier encapsulating the starch granules to limit enzymatic access and digestion. The amount of glucose release decreased significantly with increasing TG concentration, with a reduction of approximately 16% with 2% TG after 120 min of digestion. The slower rate of glucose release during the first 60 min of digestion for 2% compared to 0% TG suggested impeded first stage enzymatic access rather than second stage starch hydrolysis into glucose. Upon increasing the TG concentration, confocal microscopy revealed a denser protein network with increased connectivity, supported by a decrease in protein solubility and gelatinisation enthalpy, and increased firmness and work of shear. Therefore, transglutaminase can potentially be used to reduce starch digestibility in wheat noodles via protein network-binding.

Background: Attention deficits are found in children at familial high risk of schizophrenia (FHR-SZ) and bipolar disorder (FHR-BP) using assessment methods relying on motor-based response latency. This study compares visual attention functions in children at FHR-SZ or FHR-BP with controls using an unspeeded task unconfounded by motor components., Methods: Visual attention was assessed in 133 7-year-old children at FHR-SZ (N = 56) or FHR-BP (N = 32), and controls (N = 45) using the unspeeded paradigm, TVA-based whole report. We compared four parameters of visual attention: visual processing speed, visual short-term memory, threshold for visual perception, and error rate. Further, we investigated their potential relationships with severity of psychopathology, adequacy of the home environment, and neurocognitive measures., Results: Children at FHR-SZ displayed significant deficits in perceptual processing speed of visual attention compared with controls (p < .001; d = 0.75) as did children at FHR-BP (p < .05; d = 0.54). Visual processing speed was significantly associated with spatial working memory (β = -0.23; t(68) = -3.34, p = .01) and psychomotor processing speed (β = 0.14, t(67) = 2.11, p < .05)., Limitations: Larger group sizes would have permitted inclusion of more predictors in the search for neurocognitive and other factors associated with the parameters of TVA-based whole report., Conclusions: Young children at FHR-SZ and FHR-BP display significant deficits in processing speed of visual attention, which may reflect the effect of shared vulnerability risk genes. Early identification of children at FHR-SZ and FHR-BP with perceptual processing speed impairments may represent a low-cost basis for low-risk interventions., (Copyright © 2019. Published by Elsevier B.V.)

Importance: Children at familial high risk of schizophrenia spectrum disorders (FHR-SZ) or bipolar disorder (FHR-BP) exhibit neurocognitive impairments. Large studies of neurocognition in young children at familial high risk at the same age are important to differentiate the pathophysiology and developmental trajectory of these 2 groups., Objective: To characterize neurocognitive functions in 7-year-old children with FHR-SZ or FHR-BP and a control population., Design, Setting, and Participants: This multisite population-based cohort study collected data from January 1, 2013, to January 31, 2016, in the first wave of the Danish High Risk and Resilience Study VIA 7 at 2 university hospital research sites in Copenhagen and Aarhus using Danish registries. Participants (n = 514) included 197 children with FHR-SZ, 118 with FHR-BP, and 199 controls matched with the FHR-SZ group for age, sex, and municipality. Assessors were blinded to risk status., Exposures: Parents with schizophrenia, bipolar disorder, or neither diagnosis., Main Outcomes and Measures: Neurocognitive functions were measured across 23 tests. Four neurocognitive domains were derived by principal component analysis, including processing speed and working memory, verbal functions, executive and visuospatial functions, and declarative memory and attention., Results: A total of 514 children aged 7 years were included in the analysis (46.3% girls), consisting of 197 children with FHR-SZ (46.2% girls), 118 with FHR-BP (46.6% girls), and 199 controls (46.2% girls). Children with FHR-SZ were significantly impaired compared with controls on processing speed and working memory (Cohen d = 0.50; P < .001), executive and visuospatial functions (Cohen d = 0.28; P = .03), and declarative memory and attention (Cohen d = 0.29; P = .02). Compared with children with FHR-BP, children with FHR-SZ performed significantly poorer in processing speed and working memory (Cohen d = 0.40; P = .002), executive and visuospatial functions (Cohen d = 0.35; P = .008), and declarative memory and attention (Cohen d = 0.31; P = .03). Children with FHR-BP and controls did not differ., Conclusions and Relevance: Children with FHR-SZ had widespread neurocognitive impairments, supporting the hypothesis of neurocognitive functions as endophenotypes of schizophrenia. The absence of neurocognitive deficits in children with FHR-BP suggests distinct neurodevelopmental manifestations in these familial high-risk groups at this age. Early detection of children with FHR-SZ and cognitive impairments is warranted to investigate associations of neurocognition with transition to psychosis, add to the knowledge of their developmental pathophysiology, and inform early intervention programs.

This study aimed to compare the psychopathological profiles of children at familial high risk of schizophrenia spectrum psychosis (FHR-SZ) or bipolar disorder (FHR-BP) with population-based controls. We used Danish nationwide registers to retrieve a cohort of 522 seven-year-old children of parents with schizophrenia spectrum psychosis (N=202), bipolar disorder (N=120) or none of these disorders (N=200). Psychopathology was assessed by reports from multiple informants, including children, parents and teachers. Lifetime DSM-IV diagnoses were ascertained by blinded raters through the Schedule for Affective Disorders and Schizophrenia for School-Age Children. The dimensional assessment of psychopathology was performed by the Child Behavior Checklist, the Teacher's Report Form, a modified version of the ADHD-Rating Scale, the Test Observation Form, and the State-Trait Anxiety Inventory for Children. Current level of functioning was evaluated using the Children's Global Assessment Scale (CGAS). The prevalence of lifetime psychiatric diagnoses was significantly higher in both FHR-SZ children (38.7%, odds ratio, OR=3.5, 95% confidence interval, CI: 2.2-5.7, p < 0.001) and FHR-BP children (35.6%, OR=3.1, 95% CI: 1.8-5.3, p < 0.001) compared with controls (15.2%). FHR-SZ children displayed significantly more dimensional psychopathology on all scales and subscales compared with controls except for the Anxious subscale of the Test Observation Form. FHR-BP children showed higher levels of dimensional psychopathology on several scales and subscales compared with controls, but lower levels compared with FHR-SZ children. Level of functioning was lower in both FHR-SZ children (CGAS mean score = 68.2; 95% CI: 66.3-70.2, p < 0.0001) and FHR-BP children (73.7; 95% CI: 71.2-76.3, p < 0.05) compared with controls (77.9; 95% CI: 75.9-79.9). In conclusion, already at the age of seven, FHR-SZ and FHR-BP children show a higher prevalence of a broad spectrum of categorical and dimensional psychopathology compared with controls. These results emphasize the need for developing early intervention strategies towards this vulnerable group of children., (© 2018 World Psychiatric Association.)

Essence of chicken (EOC) beverage is a chicken meat extract, widely consumed in Asian countries for health benefits. EOC is a rich source of peptides and amino acids. White bread has become a popular staple food in all regions of Southeast Asia. A randomized controlled, crossover, non-blind trial was performed to investigate the role of EOC on glycaemic response (GR) of white bread. Ten healthy young subjects returned on five separate days for three glucose and two bread sessions. Subjects consumed bread or bread with EOC. The 120 min incremental area under the curve was significantly lower after consuming two bottles of EOC with bread than white bread alone. The glycaemic index (GI) of white bread was 83 and white bread with EOC 57. The co-ingestion of EOC may be a practical and simple way to reduce the GR of bread and other starch-based staples.

Objective: To evaluate the survival and growth potential of human preantral follicles isolated before and after cryopreservation., Design: Pilot study., Setting: Gynecology research unit in a university hospital., Patient(s): Six women aged 27 to 32 years., Intervention(s): Six ovarian biopsy samples were cut into two equal parts, half subjected to slow-freezing followed by follicle isolation (cryo-iso group) and alginate-matrigel embedding, and half immediately processed for follicle isolation and alginate-matrigel embedding followed by slow-freezing (iso-cryo group) or used as fresh controls (fresh group)., Main Outcome Measure(s): Follicle number, viability, diameter, and morphology., Result(s): After 1,134 preantral follicles had been isolated from fresh biopsy samples and 1,132 from frozen specimens, the three groups were compared before and after 7 days of in vitro culture (IVC) in alginate-matrigel beads. No statistically significant differences in viability were found between the three groups before or after IVC, but follicle diameter increased in all three groups after IVC. Morphology analysis revealed well-preserved follicles in both the iso-cryo and cryo-iso groups after IVC., Conclusion(s): Human preantral follicles can be successfully cryopreserved before or after isolation without impairing their ability to survive and grow in vitro. This could lead to development of new protocols for follicle cryopreservation, IVC, and grafting in clinical and research settings for fertility preservation., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Ovarian tissue cryopreservation is currently proposed to young cancer patients to preserve their fertility before radiochemotherapy. The potential risk is that the tissue might harbor malignant cells that could induce disease recurrence. We therefore decided to evaluate the presence of leukemic cells in cryopreserved ovarian tissue from 18 leukemic patients: 6 with chronic myeloid leukemia (CML) and 12 with acute lymphoblastic leukemia (ALL). In each case, histology, quantitative reverse-transcribed polymerase chain reaction (RT-PCR) and long-term (6 months) xenografting to immunodeficient mice were used. Histology did not identify any malignant cells in the ovarian tissue. By quantitative RT-PCR, 2 of 6 CML patients were positive for BCR-ABL in their ovarian tissue. Among the 12 ALL patients, 7 of the 10 with available molecular markers showed positive leukemic markers in their ovarian tissue (translocations or rearrangement genes). Four mice grafted with ovarian tissue from ALL patients developed intraperitoneal leukemic masses. In conclusion, this study demonstrates, by quantitative RT-PCR, ovarian contamination by malignant cells in acute as well as chronic leukemia, whereas histology fails to do so. Moreover, chemotherapy before ovarian cryopreservation does not exclude malignant contamination. Finally, reimplantation of cryopreserved ovarian tissue from ALL and CML patients puts them at risk of disease recurrence.

To compare the glycaemic index (GI) of newly developed 'atta mix' roti with whole wheat flour roti. Eighteen healthy non-diabetic subjects consumed 50 g available carbohydrate portions of a reference food (glucose) and two test foods (whole wheat flour roti and atta mix roti) in random order after an overnight fast. The reference food was tested on three separate occasions, while the test foods were each tested once. Capillary blood samples were measured from finger-prick samples in fasted subjects ( - 5 and 0 min) and at 15, 30, 45, 60, 90 and 120 min from the start of each food. No significant difference was observed between roti prepared from whole wheat flour and atta mix in terms of appearance, texture, flavour, taste or acceptability. For each test food, the incremental area under the curve and GI values were determined. The GI of atta mix roti (27.3 (sem 2.2)) was considerably lower than the whole wheat flour roti (45.1 (sem 3.5), P < 0.001). Development of foods with lower dietary glycaemic load such as the atta mix roti could help in the prevention and control of diabetes in South Asian populations, which habitually consume very high glycaemic load diets.

Background: Chemo- or radiotherapy can induce premature ovarian failure (POF), and ovarian tissue cryopreservation and transplantation may be proposed to restore ovarian function. Our aim was to evaluate the quality of oocytes and embryos derived from frozen-thawed transplanted ovarian tissue., Materials and Methods: Women were 21-28 years old at tissue cryopreservation. Nine women suffering POF following chemotherapy with or without radiotherapy underwent orthotopic ovarian tissue transplantation. After 12 months of spontaneous cycles without pregnancy, oocyte retrieval was performed in four patients during mildly stimulated or spontaneous cycles. ICSI was performed in all cases, with embryo transfer on day 3. Light and electron microscopy was used to study oocytes and embryos., Results: Signs of ovarian function restoration (estradiol peak, decreased FSH, follicular development) began 16-26 weeks after reimplantation. Twenty-one oocyte retrieval attempts were made. At least one oocyte was collected in 15 cases, giving an empty follicle rate per retrieval of 29% (6/21). Sixteen oocytes were recovered, of which 6 were abnormal or immature (38%) and 10 (62%) were in metaphase II (MII). Three MII oocytes failed to fertilize, two showed abnormal fertilization and five normal MII oocytes successfully fertilized with subsequent normal embryo development (Grade 2), yielding an embryo transfer rate of 24% per retrieval. No pregnancy occurred., Conclusions: IVF in women with orthotopically grafted frozen-thawed ovarian tissue involves a higher risk of empty follicles, abnormal or immature oocytes, and low embryo transfer rates.