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Genetic counseling for patients who are pursuing genetic testing in the absence of a medical indication, referred to as elective genomic testing (EGT), is becoming more common. This type of testing has the potential to detect genetic conditions before there is a significant health impact permitting earlier management and/or treatment. Pre- and post-test counseling for EGT is similar to indication-based genetic testing. Both require a complete family and medical history when ordering a test or interpreting a result. However, EGT counseling has some special considerations including greater uncertainties around penetrance and clinical utility and a lack of published guidelines. While certain considerations in the selection of a high-quality genetic testing laboratory are universal, there are some considerations that are unique to the selection of a laboratory performing EGT. This practice resource intends to provide guidance for genetic counselors and other healthcare providers caring for adults seeking pre- or post-test counseling for EGT. Genetic counselors and other genetics trained healthcare providers are the ideal medical professionals to supply accurate information to individuals seeking counseling about EGT enabling them to make informed decisions about testing and follow-up.

PROBLEM: Both luteal phase progesterone (P4) levels and use of the intramuscular (IM) injectable progestin-only contraceptive depo-medroxyprogesterone acetate (DMPA-IM) have been linked to increased S/HIV acquisition in animal, clinical and in vitro models. Several plausible mechanisms could explain MPA-induced HIV-1 acquisition while those for the luteal phase are underexplored. METHOD OF STUDY: Peripheral blood mononuclear cells (PBMCs) were treated with P4 and estrogen at concentrations mimicking the luteal phase, follicular phase or with levels of MPA mimicking peak serum levels in DMPA-IM users. Cells were infected with an R5-tropic infectious molecular clone and HIV-1 infection was measured. A role for the glucocorticoid receptor (GR) was investigated using the GR/PR antagonist RU486. CCR5 protein levels and activation status, assessed by levels of the activation marker CD69, were measured by flow cytometry after treatment in vitro and in PBMCs from naturally-cycling women or DMPA-IM users. RESULTS: Both MPA and luteal phase hormones significantly increased HIV-1 infection in vitro. However, MPA but not luteal phase hormones increased the CD4+/CD8+ T cell ratio, CCR5 protein expression on CD4+ T cells and increased expression of the activation marker CD69. The GR is involved in MPA-induced, but not luteal phase hormone-induced increased HIV-1 infection. In DMPA-IM users, the frequency of CCR5-expressing CD3+ and CD8+ cells was higher than for women in the luteal phase. CONCLUSIONS: MPA increases HIV-1 infection in a manner different from that of luteal phase hormones, most likely involving the GR and at least in part changes in the frequency and/or expression of CCR5 and CD69.

Microscopic organisms that penetrate calcareous structures by actively dissolving the carbonate matrix, namely microendoliths, have an important influence on the breakdown of marine carbonates. The study of these microorganisms and the bioerosion traces they produce is crucial for understanding the impact of their bioeroding activity on the carbonate recycling in environments under global climate change. Traditionally, either the extracted microendoliths were studied by conventional microscopy or their traces were investigated using scanning electron microscopy (SEM) of epoxy resin casts. A visualisation of the microendoliths in situ, that is within their complex microbioerosion structures, was previously limited to the laborious and time-consuming double-inclusion cast-embedding technique. Here, we assess the applicability of various fluorescence staining methods in combination with confocal laser scanning microscopy (CLSM) for the study of fungal microendoliths in situ in partly translucent mollusc shells. Among the tested methods, specific staining with dyes against the DNA (nuclei) of the trace making organisms turned out to be a useful and reproducible approach. Bright and clearly delineated fluorescence signals of microendolithic nuclei allow, for instance, a differentiation between abandoned and still populated microborings. Furthermore, infiltrating the microborings with fluorescently stained resin seems to be of great capability for the visualisation and quantification of microbioerosion structures in their original spatial orientation. Potential fields of application are rapid assessments of endolithic bio- and ichnodiversity and the quantification of the impact of microendoliths on the overall calcium carbonate turnover. The method can be applied after CLSM of the stained microendoliths and retains the opportunity for a subsequent investigation of epoxy casts with SEM. This allows a three-fold approach in studying microendoliths in the context of their microborings, thereby fostering the integration of biological and ichnological aspects of microbial bioerosion.Bioerosion describes the process of active erosion of hard substrates induced by the activity of living organisms. Beside numerous marine macroscopic bioeroding organisms such as sponges, annelids or bivalves, there is an astonishing ‘hidden diversity’ of microscopic bioeroding organisms which produce minute tunnels and chambers, for example in calcareous shells and skeletons of other marine organisms. These so-called microendoliths belong to bacteria, microalgae, foraminiferans, or fungi. Due to their lifestyle hidden inside the hard substrate, scientific investigation is often laborious and involves complex preparation techniques, electron microscopy, or even nano-computed tomography. Photo-autotrophic microendoliths (eg cyanobacteria and algae) have been studied with fluorescence microscopy using autofluorescence properties, for example of their chloroplasts. However, microendoliths of aphotic depths, mostly of fungal origin, do not show autofluorescence. With the present study we test different fluorescent dyes staining the microbioeroders ‘in situ’, that is, inside their microscopic tunnels, and visualise them using three-dimensional confocal laser scanning microscopy (CLSM). Very good results have been obtained with the dye Sybr Green I that stains DNA molecules and thereby the cell nuclei of the microendoliths. This method can be used, for instance, to measure the infestation rate of a given substrate by discriminating between abandoned microborings and those still inhabited by microendoliths. Another approach that was successfully tested in the course of the present study was the infiltration of the cleaned microborings with resin that was previously mixed with the fluorescent dye Safranin-O. The datasets obtained with the CLSM were used to reconstruct 3D-surface models of the microborings of three different microendoliths. Such models can be used to analyse the original spatial arrangement inside the hard substrate and to measure exact volumes. The resulting possibility to make exact quantifications is of high value for future investigations that focus on the role and proportion of microbioerosion in the (re)cycling of marine carbonates.

Glyco‐assemblies derived from amphiphilic sugar‐decorated block copolymers (ASBCs) have emerged prominently due to their wide application, for example, in biomedicine and as drug carriers. However, to efficiently construct these glyco‐assemblies is still a challenge. Herein, we report an efficient technology for the synthesis of glyco‐inside nano‐assemblies by utilizing RAFT polymerization of a galactose‐decorated methacrylate for polymerization‐induced self‐assembly (PISA). Using this approach, a series of highly ordered glyco‐inside nano‐assemblies containing intermediate morphologies were fabricated by adjusting the length of the hydrophobic glycoblock and the polymerization solids content. A specific morphology of complex vesicles was captured during the PISA process and the formation mechanism is explained by the morphology of its precursor and intermediate. Thus, this method establishes a powerful route to fabricate glyco‐assemblies with tunable morphologies and variable sizes, which is significant to enable the large‐scale fabrication and wide application of glyco‐assemblies., Glyco‐inside nano‐assemblies containing numerous intermediate morphologies are fabricated by leveraging RAFT polymerization of a galactose‐decorated monomer for polymerization‐induced self‐assembly. This method establishes a powerful route to fabricate glyco‐inside nano‐assemblies with tunable morphologies and variable sizes, which is significant to expand the large‐scale fabrication and wide application of glyco‐assemblies.

Objectives: To estimate the population prevalence of severe fear of childbirth (FOC) during pregnancy and investigate its association with: (a) antenatal common mental disorders (depression and anxiety disorder) and (b) elective cesarean birth. / Methods: 545 participants from an inner-city London maternity population were interviewed soon after their first antenatal appointment (mean gestation: 14 weeks). Current mental disorders were assessed using the Structured Clinical Interview DSM-IV. FOC was measured using the Wijma Delivery Expectancy/Experience Questionnaire (WDEQ-A) at approximately 28 weeks gestation (n = 377), with severe FOC defined using a cutoff of WDEQ-A ≥ 85. Birth mode information was collected at 3 months post-delivery using an adapted Adult Service Use Schedule. Linear regressions were used to model associations, adjusting for the effects of covariates (age, parity, relationship status, education, and planned pregnancy). Sampling weights were used to adjust for bias introduced by the stratified sampling. We also accounted for missing data within the analysis. / Results: The estimated population prevalence of severe FOC was 3% (95% CI: 2%-6%) (n = 377). Depression and anxiety were significantly associated with severe FOC after adjustment for covariates (45% vs 11%; coefficient: 15.75, 95% CI: 8.08-23.42, P < .001). There was a weak association between severe FOC and elective cesarean birth. / Conclusions: Severe FOC occurs in around 3% of the population. Depression and anxiety are associated with FOC. Pregnant people with depression and anxiety may be at increased risk of experiencing severe FOC. Attitudes toward childbirth should be assessed as part of routine clinical assessment of pregnant people in contact with mental health services.

Objectives\ud Questionnaires used to assess women’s beliefs as a predictor of breastfeeding behaviour are not theoretically informed or tested for psychometric validity and reliability. This study conducted a psychometric evaluation of the Beliefs About Breastfeeding Questionnaire (BAB-Q).\ud \ud Design\ud A two-phase evaluation in an online cross-sectional questionnaire study (N = 278) and cohort study sample (N = 264). A ten-item questionnaire was proposed to assess women’s beliefs about the benefits and efforts of breastfeeding.\ud \ud Methods\ud Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) assessed construct validity and reliability. Multivariate regression analyses assessed validity in predicting breastfeeding behaviour and experiences.\ud \ud Results\ud EFA found a shortened 8-item, 2-factor model had good fit (χ2 = 23.3, df = 13, p < .040; CFI = .99, TLI = .99, RMSEA = .05), with significant factor loadings. Factor 1 (benefit beliefs) and factor 2 (effort beliefs) accounted for 47 and 19.4% of the explained variance and correlated moderately (r = −.40). CFA confirmed the solution in the cohort sample (χ2 = 49.6 df = 19, p < .010; CFI = .97, TLI = .96, and RMSEA = .078). Adjusted regression analyses found beliefs did not reliably predict infant feeding practices. Women’s beliefs significantly predicted the likelihood that women experienced breastfeeding as ‘much more’ positive and negative than they expected.\ud \ud Conclusions\ud The eight-item questionnaire showed good model fit with acceptable loadings, and good reliability for all subscales. The utility of the BAB-Q at predicting breastfeeding behaviour remains unclear and unsupported by empirical evidence. Further assessments of the predictive validity of the questionnaire in longitudinal studies with diverse beliefs and infant feeding practices are required.

This study investigated middle childhood resting electroencephalography (EEG) and behavioral adjustment in 35 internationally adopted children removed from early caregiving adversity between 6 and 29 months of age. Older age of adoption was associated with more immature or atypical profiles of middle childhood cortical function, based on higher relative theta power (4-6 Hz), lower relative alpha power (7-12 Hz), lower peak alpha frequency, and lower absolute beta (13-20 Hz) and gamma (21-50 Hz) power. More immature or atypical EEG spectral power indirectly linked older age of adoption with increased risk for externalizing problems in middle childhood. The findings add to existing evidence linking duration of early adverse exposures with lasting effects on brain function and behavioral regulation even years after living in a stable adoptive family setting. Findings underscore the need to minimize and prevent children's exposures to early caregiving adversity, especially in the first years of life. They call for innovative interventions to support neurotypical development in internationally adopted children at elevated risk.

Blockchains, a disruptive technology with potentially many applications in modern-day supply chain (SC) transactions, have not been adequately reflected by theory. Researchers and business managers must understand where and when blockchains’ application may be expected and investigated. The present study clarifies the discussion about blockchain application areas (BAAs) in SC transactions and their relevance for businesses. This study combines the findings from three methodological approaches: an extant literature review, a Delphi study, and a survey of 151 German machinery and equipment sector business managers. The results further our understanding of blockchains’ business opportunities among SC transactions and verify and extend Iansiti and Lakhani’s (Harvard Business Review 2017; 95: 118) blockchain adoption framework. Verified customer reviews and product quality certification are identified as the most relevant blockchain usages in SC transactions. Interestingly, we anticipate the least likely adoption of blockchains to occur for document-signing processes despite arguments within the literature that suggest otherwise. Two newly identified BAAs—logistics and delivery systems—and token-curated registries rank among the top four most relevant. The present study’s valuation of BAAs advances theory and will likely affect business strategies by indicating where, when, and why businesses should participate in blockchain networks.

Pathogenic variants in the cyclin-dependent kinase-like 5 (CDKL5) gene cause the neurodevelopmental disorder, the CDKL5 deficiency disorder. Reports of individuals with pathogenic variants in CDKL5 without seizures are exceedingly rare, and in-depth analyses of their variants have been lacking. Whole-genome sequencing was performed on a 29-year-old female with mild intellectual disability who, in the absence of overt seizures, presented with multiple episodes of altered mental status over a 24-year period. Clinical history was supplemented by a parent completed questionnaire from the International CDKL5 Disorder Database. We identified a de novo heterozygous variant in CDKL5 (NM_003159.2:c.645T>A;p.Ser215Arg). In-depth computational analysis performed to predict the impact of the variant on protein structure and function demonstrated that the variant was likely pathogenic. In this light, cell-based studies showed that the S215R substitution causes a marked reduction in CDKL5 kinase activity. Similarities between our case and one previously reported case are striking. These cases, both without seizures but with apparent behavioral symptomatology, together question whether seizures are mandatory in this neurodevelopmental disorder.

Objective To estimate prevalence of lifetime and current eating disorders (ED) in a sample of pregnant women in South‐East London and to describe their sociodemographic and clinical characteristics. Method Secondary analysis of data from a cross‐sectional survey. Using a stratified sampling design, 545 pregnant women were recruited. Diagnostic interviews were administered to assess lifetime and current ED, depression, anxiety, and borderline personality disorder. Data were extracted from maternity records to assess identification of ED in antenatal care. Estimates of population prevalence of ED were obtained using sampling weights to account for the stratified sampling design. Results Weighted prevalence of lifetime ED was 15.35% (95% confidence interval [CI] [11.80, 19.71]), and current ED was 1.47% (95% CI [0.64, 3.35]). Depression, anxiety, and history of deliberate self‐harm or attempted suicide were common in pregnant women with ED. Identification of ED in antenatal care was low. Conclusions Findings indicate that by early pregnancy, a significant proportion of pregnant women will have had ED, although less typically during pregnancy, and psychiatric comorbidity is common. Yet ED were poorly recognised in antenatal care. The findings highlight the importance of increasing awareness about maternal ED to improve identification and response to the healthcare needs of pregnant women with ED.

Background Genome sequencing (GS) of individuals without a medical indication, known as elective GS, is now available at a number of centers around the United States. Here we report the results of elective GS and pharmacogenetic panel testing in 52 individuals at a private genomics clinic in Alabama. Methods Individuals seeking elective genomic testing and pharmacogenetic testing were recruited through a private genomics clinic in Huntsville, AL. Individuals underwent clinical genome sequencing with a separate pharmacogenetic testing panel. Results Six participants (11.5%) had pathogenic or likely pathogenic variants that may explain one or more aspects of their medical history. Ten participants (19%) had variants that altered the risk of disease in the future, including two individuals with clonal hematopoiesis of indeterminate potential. Forty‐four participants (85%) were carriers of a recessive or X‐linked disorder. All individuals with pharmacogenetic testing had variants that affected current and/or future medications. Conclusion Our study highlights the importance of collecting detailed phenotype information to interpret results in elective GS., Genome sequencing (GS) of individuals without a medical indication is referred to as elective GS. Among 52 individuals undergoing elective GS, 11.5% (6/52) had pathogenic or likely pathogenic variants that may explain one or more aspects of their medical history, 19% (10/52) had variants that altered the risk of disease in the future, including two individuals with clonal hematopoiesis of indeterminate potential, 85% (44/52) were carriers of a recessive or X‐linked disorder, and 100% of individuals with pharmacogenetic testing had variants that affected current and/or future medications.

Children reared in socioeconomically disadvantaged environments are at risk for academic, cognitive, and behavioral problems. Mounting evidence suggests that childhood adversities, encountered at disproportionate rates in contexts of socioeconomic risk, shape the developing brain in ways that explain disparities. Circuitries that subserve neurocognitive functions related to memory, attention, and cognitive control are especially affected. However, most work showing altered neural function has focused on middle childhood and adolescence. Understanding alterations in brain development during foundational points in early childhood is a key next step. To address this gap, we examined functional near-infrared-spectroscopy-based neural activation during a working memory (WM) task in young children aged 4-7 years (N = 30) who varied in socioeconomic risk exposure. Children who experienced greater disadvantage (lower income to needs ratio and lower Hollingshead index) exhibited lower activation in the lateral prefrontal cortex than children who experienced less to no disadvantage. Variability in prefrontal cortex activation, but not behavioral performance on the WM task, was associated with worse executive functioning in children as reported by parents. These findings add to existing evidence that exposure to early adversity, such as socioeconomic risk, may lead to foundational changes in the developing brain, which increases risk for disparities in functioning across multiple cognitive and social domains.

Human immunodeficiency virus (HIV)‐positive women can breastfeed with minimal risk of mother‐to‐child transmission if taking antiretrovirals. Guidelines surrounding infant feeding for HIV‐positive women have evolved several times over the last two decades. Our review aimed to explore perspectives of breastfeeding with antiretrovirals from HIV‐positive women since the World Health Organization (2010) infant feeding and antiretroviral guidelines. HIV‐positive pregnant and postnatal women from all countries/settings were eligible. HIV‐positive women were either on an antiretroviral regimen at the time of the study, previously on an antiretroviral regimen, not initiated on a regimen yet, or enrolled in prevention of mother‐to‐child transmission (PMTCT) care. Quality assessment of all included studies were conducted. Four databases (CINAHL, EMBASE, MEDLINE and PsycINFO) were searched for studies conducted from January 2010 to October 2020. Nine papers were included in the review, of which two presented findings from the same study. Five analytical themes were developed via thematic synthesis: (1) awareness of breastfeeding with antiretrovirals, (2) turmoil of emotions, (3) coping mechanisms, (4) the intertwining of secret, stigma and support and (5) support needed. Support from family and health care professionals and coping approaches were important to overcome stigma and the emotional challenges of breastfeeding with antiretrovirals. Health care professionals should be familiar with the most updated national and local guidance surrounding infant feeding and antiretrovirals. Further research into interventions to encourage HIV‐positive women to adhere and commit to lifelong antiretroviral treatment (Option B+) for breastfeeding is required.

The breastfeeding intention–behaviour gap remains wide in developed countries. Current studies have focused on maternal attitudes and behaviours concerning infant feeding in order to explore barriers to breastfeeding continuation. There has been limited consideration of the impact of paternal attitudes and behaviours, despite contemporary parenthood evolving and evidence indicating that there are greater levels of paternal involvement in routine childcare tasks. This mixed‐methods study used a triangulation design to examine the associations between paternal attitudes towards parenthood and infant‐feeding methods, levels of paternal involvement, infant‐feeding outcomes, and father–infant relationships. Fathers of infants

The health benefits of breastfeeding are well recognised, but breastfeeding rates worldwide remain suboptimal. Breastfeeding outcomes have yet to be explored among women who give birth to macrosomic (birthweight ≥4000 g) infants, a cohort for whom the benefits of breastfeeding may be particularly valuable, offering protection against later-life morbidity associated with macrosomia. This longitudinal prospective cohort study aimed to identify whether women who give birth to macrosomic infants are at greater risk of breastfeeding non-initiation or exclusive breastfeeding (EBF) cessation. A total of 328 women in their third trimester were recruited from hospital and community settings and followed to 4 months post-partum. Women gave birth to 104 macrosomic and 224 non-macrosomic (