Investigating relationships among cancer survivors' engagement in an online support community, social support perceptions, well-being, and moderating effects of existing (offline) social support.

PURPOSE: Socially supportive relationships help cancer survivors cope with their diagnosis and may improve quality of life; however, many survivors report unmet support and information needs. Online communities of survivors may address these needs, but research on their benefits have been equivocal. This cross-sectional, self-report study investigated relationships among cancer survivors' level of engagement in an online survivor community (The American Cancer Society Cancer Survivors Network®; CSN), perceptions of emotional/informational support available from online communities ("online social support"), well-being, and moderating effects of "offline social support." METHODS: Participants were 1255 registered users of the CSN who completed surveys between 2013 and 2014. Three types of engagement with the CSN-social/communal, interpersonal communication, and informational/search engagement-were identified through principal components analysis. Regression analyses examined hypotheses. RESULTS: More frequent social/communal and interpersonal communication engagement were associated with increased online social support (p < .0001), and the relationship between interpersonal communication engagement and online social support was strongest for survivors reporting lower offline social support (interaction ß = - .35, p < .001). Greater online social support was associated with increased well-being, but only among survivors reporting low offline social support (interaction ß = - .35, p < .0001). CONCLUSIONS: Engagement in online survivor communities may increase support perceptions that promote well-being, but benefits may accrue more to survivors reporting low offline social support. IMPLICATIONS FOR CANCER SURVIVORS: Newly diagnosed cancer survivors, particularly those with unmet emotional/informational support needs, should be given the opportunity to communicate with other survivors through online survivor support networks.

Integration of microarray technology into prenatal diagnosis: counselling issues generated during the NICHD clinical trial.

Cytogenetic microarray analysis (CMA) in prenatal testing detects chromosome abnormalities and new genetic syndromes that would be missed by conventional cytogenetics and has the potential to significantly enhance prenatal genetic evaluation. A large Eunice Kennedy Shriver National Institute Of Child Health and Human Development (NICHD)-sponsored multicentered trial to assess the role of CMA as a primary prenatal diagnostic tool has been completed, and results will soon be available. Integration of this technology into clinical care will require thoughtful changes in patient counseling. Here, we examine four cases, all ascertained in the NICHD prenatal microarray study, to illustrate the challenges and subtleties of genetic counseling required with prenatal CMA testing. Although the specifics of each case are distinct, the underlying genetic principles of uncertainty, variable expressivity, and lack of precise genotype-phenotype correlation are well known and already part of prenatal counseling. Counselor and practitioner education will need to include both the science of interpreting array findings as well as development of improved approaches to uncertainty. A team approach to interpretation will need to be developed, as will standardized guidelines by professional organizations and laboratories. Of equal import is additional research into patient attitudes and desires, and a better understanding of the full phenotypic spectrum of copy number variants discovered in utero.

High-Resolution genomic arrays identify CNVs that phenocopy the chromosome 22q11.2 deletion syndrome.

The 22q11 Deletion Syndrome includes the overlapping phenotypes of DiGeorge/Velocardiofacial Syndromes, characterized by conotruncal heart defects, cleft palate, thymus, and parathyroid gland dysplasia. The majority (90%) of patients harbor detectable chr22q11.2 deletions, but a genetic etiology for the remainder of patients without a deletion can remain undefined despite major birth defects. We analyzed DNA from eight patients with normal 22q11 FISH studies by high-density single nucleotide polymorphism (SNP) arrays and identified potentially pathogenic copy number variants (CNVs) in four of eight patients. Two patients showed large CNVs in regions of known genomic disorders: one a deletion of distal chr22q11.2 and the other a duplication of chr5q35. A 3-Mb deletion of chr19p13.3 that includes a gene associated with conotruncal heart defects was found in a third patient. Two potentially pathogenic CNVs were found in a fourth patient: a large heterozygous deletion of chr6p24 and a smaller duplication of chr9p24. Our findings support a recent consensus statement advocating chromosomal microarray analysis as a first-line diagnostic approach for patients with multiple congenital anomalies. In patients with phenotypes suggestive of the 22q11.2 syndrome spectrum and normal FISH, microarray analysis can uncover the molecular basis of other genomic disorders whose features overlap those of 22q11.2 deletions.

Physicians' communication of Down syndrome screening test results: the influence of physician numeracy.

PURPOSE: We investigated three questions: (1) How do obstetrician-gynecologists communicate positive and negative test results? (2) When reporting screening test results, do obstetrician-gynecologists use quantitative or qualitative information? and (3) Is physician numeracy (i.e., the ability to use and understand numbers) associated with use of quantitative or qualitative information? METHOD: Obstetrician-gynecologists (N = 203; 55.6% response rate) who were members of the American College of Obstetricians and Gynecologists completed a survey about their communication of Down syndrome screening test results, an Objective Numeracy Scale, and the Subjective Numeracy Scale. RESULTS: Higher scores on the Subjective Numeracy Scale and younger age predicted obstetrician-gynecologists' use of numbers to explain testing results. The Objective Numeracy Scale did not predict use of numbers. Gender was correlated with scores on the Subjective Numeracy Scale (r = 0.2) and the Subjective Numeracy Scale-Ability Subscale (r = 0.3), with men scoring higher than women when controlling for age. Open-ended questions revealed that communication strategies vary, with approximately one in three obstetrician-gynecologists providing numerical information, and frequency format being the commonly used numerical format. CONCLUSION: Although physicians are often overlooked in the problem of low health literacy, it is important that we continue to investigate the impact of physician numeracy on patient care.

Challenges faced by cancer patients in Uganda: Implications for health systems strengthening in resource limited settings.

BACKGROUND: Uganda Cancer Institute (UCI), the only comprehensive cancer treatment center in Uganda, registers about 4000 new cancer patients a year. However, many cancer patients in Uganda never receive treatment due to a variety of challenges. We therefore conducted a study to identify and assess the challenges faced by cancer patients in Uganda. METHODS: A cross-sectional study conducted in April-May 2017 among adult cancer patients. 359 participants participated in an interviewer-administered survey. We used stratified random sampling to select the study participants. Data was analyzed in SPSS Statistics 24. RESULTS: 35 % of the patients delayed initiating cancer treatment and 41 % missed medical appointments along their care journey. Delayed and missed appointments were mainly due to lack of money for cancer medicines, transportation and accommodation. Patients also expressed challenges with side effects of cancer treatment: 52 % sought help from health workers when they experienced side effects; 14 % used alternative medicine; and 21 % did not inform anyone. In addition, 55 % of the participants had limited knowledge about their disease and treatment. Other challenges when at UCI included: being hungry and thirsty throughout the day, long waiting hours, not having a resting place, not understanding what comes next, and having their records lost by hospital staff. CONCLUSION: Challenges faced by cancer patients in Uganda result in enormous delays in initiation and continuation of cancer treatment. These challenges are often a result of the poor social-economic status of the patients; inadequate infrastructure for cancer care; and inefficiencies in the health care system. POLICY SUMMARY: To improve the experience of patients, the National Cancer Control Plan should consider establishing regional cancer centers; creating a reliable supply of cancer medicines; and integrating navigation programmes into cancer care. Strengthening the whole health system, in relation to cancer service delivery, should remain a top priority for Uganda and other resource limited settings.

Explaining the Black-White Disparity in Preterm Birth: A Consensus Statement From a Multi-Disciplinary Scientific Work Group Convened by the March of Dimes.

In 2017-2019, the March of Dimes convened a workgroup with biomedical, clinical, and epidemiologic expertise to review knowledge of the causes of the persistent Black-White disparity in preterm birth (PTB). Multiple databases were searched to identify hypothesized causes examined in peer-reviewed literature, 33 hypothesized causes were reviewed for whether they plausibly affect PTB and either occur more/less frequently and/or have a larger/smaller effect size among Black women vs. White women. While definitive proof is lacking for most potential causes, most are biologically plausible. No single downstream or midstream factor explains the disparity or its social patterning, however, many likely play limited roles, e.g., while genetic factors likely contribute to PTB, they explain at most a small fraction of the disparity. Research links most hypothesized midstream causes, including socioeconomic factors and stress, with the disparity through their influence on the hypothesized downstream factors. Socioeconomic factors alone cannot explain the disparity's social patterning. Chronic stress could affect PTB through neuroendocrine and immune mechanisms leading to inflammation and immune dysfunction, stress could alter a woman's microbiota, immune response to infection, chronic disease risks, and behaviors, and trigger epigenetic changes influencing PTB risk. As an upstream factor, racism in multiple forms has repeatedly been linked with the plausible midstream/downstream factors, including socioeconomic disadvantage, stress, and toxic exposures. Racism is the only factor identified that directly or indirectly could explain the racial disparities in the plausible midstream/downstream causes and the observed social patterning. Historical and contemporary systemic racism can explain the racial disparities in socioeconomic opportunities that differentially expose African Americans to lifelong financial stress and associated health-harming conditions. Segregation places Black women in stressful surroundings and exposes them to environmental hazards. Race-based discriminatory treatment is a pervasive stressor for Black women of all socioeconomic levels, considering both incidents and the constant vigilance needed to prepare oneself for potential incidents. Racism is a highly plausible, major upstream contributor to the Black-White disparity in PTB through multiple pathways and biological mechanisms. While much is unknown, existing knowledge and core values (equity, justice) support addressing racism in efforts to eliminate the racial disparity in PTB.

Pregnancy with Friedreich ataxia: a retrospective review of medical risks and psychosocial implications.

OBJECTIVE: Friedreich ataxia (FRDA) is an autosomal recessive, neurodegenerative disease. Recent medical advances have improved the average life expectancy, and as such, many female patients are contemplating pregnancy. However, little research exists exploring the medical or psychosocial complications that arise from pregnancy with this disease. STUDY DESIGN: In this study, we retrospectively examined 31 women with FRDA who had 65 pregnancies, resulting in 56 live offspring. RESULTS: FRDA did not appear to increase the risk of spontaneous abortion, preeclampsia, or preterm birth. Despite the sensory and proprioceptive loss that occurs in FRDA, nearly four fifths of births were vaginal. Of babies, 94.4% were discharged home with their mothers. Equal numbers of women reported that pregnancy made their disease symptoms worse, better, or unchanged. CONCLUSION: This study demonstrates that women with FRDA can have uncomplicated pregnancies that do not uniformly complicate disease symptomatology.

National Institutes of Health State-of-the-Science Conference Statement: Family History and Improving Health.

National Institutes of Health consensus and state-of-the science statements are prepared by independent panels of health professionals and public representatives on the basis of 1) the results of a systematic literature review prepared under contract with the Agency for Healthcare Research and Quality (AHRQ); 2) presentations by investigators working in areas relevant to the conference questions during a 2-day public session; 3) questions and statements from conference attendees during open discussion periods that are part of the public session; and 4) closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the panel and is not a policy statement of the National Institutes of Health or the U.S. government. The statement reflects the panel's assessment of medical knowledge available at the time the statement was written. Thus, it provides a "snapshot in time" of the state of knowledge on the conference topic. When reading the statement, keep in mind that new knowledge is inevitably accumulating through medical research.

Screening for fetal aneuploidy and neural tube defects.

Maternal serum screening for neural tube defects and fetal aneuploidy in the second trimester has been incorporated into obstetrical practice over the past two decades. Now, as a result of several multicenter trials, first trimester screening between 11 and 14 weeks has been shown to be an effective and reliable screening test for Down syndrome and trisomy 18. This policy updates the American College of Medical Genetics policy statement entitled Second Trimester Maternal Serum Screening for Fetal Open Neural Tube Defects and Aneuploidy (2004), incorporates First trimester diagnosis and screening for fetal aneuploidy (2008) and complements the sections of American College of Medical Genetic's Standards and Guidelines for Clinical Genetics Laboratories entitled Prenatal Screening for Down syndrome (2005) and Prenatal Screening for Open Neural Tube Defects (2005).

Screening for Down syndrome: changing practice of obstetricians.

OBJECTIVE: We sought to assess the impact of American College of Obstetrician and Gynecologists (ACOG) guidelines on the practices and knowledge of obstetricians regarding screening for Down syndrome 1 year later. STUDY DESIGN: A questionnaire on Down syndrome screening was mailed to 968 ACOG Fellows and Junior Fellows. RESULTS: The response rate was 53%. The majority (95%) of respondents offer Down syndrome screening to all pregnant patients; 70% of general obstetricians offer the first-trimester screen and 86% the quad screen. Almost two-thirds (63%) of respondents are offering patients >/= 1 combination of first- and second-trimester screening tests. For women aged < 35 years, 70% offer amniocentesis selectively and 15% routinely. Chorionic villus sampling is offered less frequently. Respondents who more closely read the bulletin were more likely to say their practice had changed, answered more knowledge questions correctly, and felt more qualified to counsel patients. Most (85%) obstetricians personally counsel patients about Down syndrome risk and screening tests. The majority (94-95%) of respondents have access to adequate resources for screening within a 90-minute drive. CONCLUSION: Obstetricians have adopted a new paradigm for Down syndrome screening. First-trimester screening has been incorporated into prenatal care. Experience with these current screening tests will likely influence future guidelines and challenge the long-standing tradition of offering diagnostic testing based on maternal age. This study highlights the need for concise, unambiguous guidelines and a need to address unresolved issues in Down syndrome screening.

Evaluation of potential modifiers of the cardiac phenotype in the 22q11.2 deletion syndrome.

BACKGROUND: The phenotype associated with deletion of the 22q11.2 chromosomal region is highly variable, yet little is known about the source of this variability. Cardiovascular anomalies, including tetralogy of Fallot, truncus arteriosus, interrupted aortic arch type B, perimembranous ventricular septal defects, and aortic arch anomalies, occur in approximately 75% of individuals with a 22q11.2 deletion. METHODS: Data from 343 subjects enrolled in a study of the 22q11.2 deletion syndrome were used to evaluate potential modifiers of the cardiac phenotype in this disorder. Subjects with and without cardiac malformations, and subjects with and without aortic arch anomalies were compared with respect to sex and race. In addition, in the subset of subjects from whom a DNA sample was available, genotypes for variants of four genes that are involved in the folate-homocysteine metabolic pathway and that have been implicated as risk factors for other birth defects were compared. Five variants in four genes were genotyped by heteroduplex or restriction digest assays. The chi-square or Fisher's exact test was used to evaluate the association between the cardiac phenotype and each potential modifier. RESULTS: The cardiac phenotype observed in individuals with a 22q11.2 deletion was not significantly associated with either sex or race. The genetic variants that were evaluated also did not appear to be associated with the cardiovascular phenotype. CONCLUSIONS: Variation in the cardiac phenotype observed between individuals with a 22q11.2 deletion does not appear to be related to sex, race, or five sequence variants in four folate-related genes that are located outside of the 22q11.2 region.

First trimester diagnosis and screening for fetal aneuploidy.

Maternal serum screening for neural tube defects and fetal aneuploidy in the second trimester has been incorporated into obstetrical practice over the past two decades. Now, as a result of several multicenter trials, first trimester screening between 11 and 14 weeks has been shown to be an effective and reliable screening test for Down syndrome and trisomy 18. Benefits of first trimester screening include earlier identification of the pregnancy at risk for fetal aneuploidy and anatomic defects, in particular, cardiac anomalies, and the option of earlier diagnosis by chorionic villus sampling, if available. This policy updates the American College of Medical Genetics policy statement entitled Second Trimester Maternal Serum Screening for Fetal Open Neural Tube Defects and Aneuploidy (2004) and complements the sections of American College of Medical Genetic's Standards and Guidelines for Clinical Genetics Laboratories entitled "Prenatal screening for Down syndrome that includes first trimester biochemistry and/or ultrasound measurements."

Insulin-like factor 3 levels in amniotic fluid of human male fetuses.

BACKGROUND: Rodent studies suggest that the peptide hormone insulin-like factor 3 (Insl3) made by the fetal testis is responsible for the first transabdominal phase of testicular descent, and may be affected by xenobiotics to disrupt male reproductive tract development. To date, there is very little information on the production of INSL3 by the human fetus during gestation. The objective of the present study was to determine the concentrations and time course during pregnancy of INSL3 and testosterone production in human fetuses and their associations with maternal characteristics, pregnancy complications and outcome. METHODS: This is a retrospective cohort study in which women who contributed amniotic fluid specimens to a bank from 2003-2006 were followed to determine their pregnancy complications and pregnancy outcome. Amniotic fluid specimens were collected from the Reproductive Genetics Laboratory of the Hospital of the University of Pennsylvania subsequent to routine amniocentesis. INSL3 and total testosterone levels were measured in amniotic fluid (from n = 50 female, n = 237 male fetuses) by validated immunoassays and correlated with maternal characteristics, pregnancy complications and outcomes. RESULTS: INSL3 was only detectable in amniotic fluid from male fetuses, and highest levels occurred from weeks 15-17 of gestation. INSL3 concentration was positively associated with increased birth weight, the occurrence of pre-eclampsia and advanced maternal age, but not with testosterone levels. CONCLUSIONS: INSL3 concentration in human amniotic fluid is potentially predictive of fetal sex and pre-eclampsia, and presumably reflects the functioning of the fetal Leydig cell population.

Characterization of a putative ovarian oncogene, elongation factor 1alpha, isolated by panning a synthetic phage display single-chain variable fragment library with cultured human ovarian cancer cells.

PURPOSE: In an effort to identify cell surface targets and single short-chain antibody (scFv) for ovarian cancer therapy, we used a phage display approach to isolate an antibody with high reactivity against ovarian cancer. EXPERIMENTAL DESIGN: A phage scFv library was subjected to panning against human SK-OV-3 ovarian cancer cells. A clone with high reactivity was selected and tested in immunoperoxidase staining on a panel of normal tissues and ovarian carcinoma. Using immunoprecipitation, a differentially expressed band was analyzed by mass spectrometry. The antigen subclass was characterized with reverse transcription-PCR on cDNA library of normal tissues, and 91 ovarian cancer specimens, and correlated with clinicohistopathologic characteristics. RESULTS: Ninety-six individual scFv clones were screened in ELISA following panning. scFv F7 revealed high reactivity with ovarian cancer cell lines and showed intense staining of 15 fresh ovarian cancer specimens and no staining of a panel of normal tissues. A 40-kDa protein was identified to be translation elongation factor 1alpha1 (EEF1A1; P < 0.05). The expression of EEF1A2, a highly homologous and functionally similar oncogene, was found to be restricted only to the normal tissues of the heart, brain, and skeletal muscle. Aberrant EEF1A2 mRNA expression was found in 21 of 91 (23%) of ovarian cancer specimens and significantly correlated with increased likelihood of recurrence (P = 0.021). CONCLUSIONS: scFv F7 may represent an ovarian cancer-specific antibody against translation EEF1A family of translational factors. We propose that EEF1A2 may be a useful target for therapy of human ovarian cancer.

Author Correction: Enabling precision medicine in neonatology, an integrated repository for preterm birth research.

The original version of the Data Descriptor contained errors in the author list and affiliations. Rita Leite's first name was misspelled as "Rite" and affiliations 4 and 5 were incorrectly swapped. In addition, members of the March of Dimes Prematurity Research Center consortium were not listed in the agreed positions within the author list. These errors have now been corrected in the HTML and PDF versions.

Expression of synovial sarcoma X (SSX) antigens in epithelial ovarian cancer and identification of SSX-4 epitopes recognized by CD4+ T cells.

PURPOSE: Synovial sarcoma X (SSX) breakpoint genes are expressed in a variety of cancers but not in normal tissues, except for testis, and are potential targets for immunotherapy. The aims of this study were to determine the expression and immunogenicity of these antigens in patients with epithelial ovarian cancer (EOC). EXPERIMENTAL DESIGN: SSX-1-, SSX-2-, and SSX-4-specific reverse transcription-PCR were done on a panel of EOC specimens. Sera from a subgroup of the patients were tested for SSX-2 and SSX-4 antibody by ELISA and recombinant antigen expression on yeast surface (RAYS). In vitro stimulation of peripheral blood mononuclear cells from a patient bearing SSX-4-expressing tumor with a pool of long peptides spanning the protein sequence was used for assessment of SSX-4-specific CD4(+) T cells recognizing distinct antigenic sequences restricted by HLA class II alleles. RESULTS: Our results indicate expression of SSX-1, SSX-2, and SSX-4 in 2.5%, 10%, and 16% of 120 EOC specimens, respectively. When all three SSX antigens are considered, aberrant expression was found in 26% of ovarian tumors. Antibodies to SSX-2 and SSX-4 were detectable by ELISA and RAYS in two patients. SSX-4-specific CD4(+) T cells recognizing two previously undescribed SSX-4-derived T-cell epitopes in association with HLA-DR (SSX-4: 51-70 and SSX-4: 61-180) were identified. CONCLUSIONS: Our study shows aberrant expression of SSX antigens in a proportion of patients with EOC. The evidence of humoral immunity to SSX-2 and SSX-4, and SSX-4-specific CD4(+) T cells among circulating lymphocytes in patients with antigen expressing EOC suggest that these antigens are attractive targets for specific immunotherapy in EOC.

OY-TES-1 expression and serum immunoreactivity in epithelial ovarian cancer.

OY-TES-1 is a novel target that belongs to the family of 'cancer/testis' (CT) antigens. Our goal was to examine the expression and immunogenicity of OY-TES-1 in epithelial ovarian cancer (EOC) to determine its potential as a target for vaccine therapy. OY-TES-1 expression was determined by one-step reverse transcriptase PCR on 100 EOC samples, 5 EOC cell lines, and a panel of normal tissues. Immunohistochemistry (IHC) was performed on the same panel of EOC tissues. Sera from a sub-group of patients were tested for OY-TES-1 antibody by ELISA. Thymus and leukocytes were weakly positive for OY-TES-1 while the remaining 5 normal tissues were negative. Expression of OY-TES-1 by either RT-PCR and/or IHC was demonstrable in 69/100 (69%) tumors. Humoral immunity to OY-TES-1 was demonstrated in 1/10 (10%) serum samples from patients whose tumors expressed the antigen. The median follow-up of the patient population was 34 months. There was no correlation between antigen expression and stage, grade, histology and survival. OY-TES-1 is expressed in 69% of patients with EOC, is absent from normal ovarian tissue, and a proportion of patients show evidence of a specific humoral immune response. These findings make OY-TES-1 an attractive target for antigen-specific immunotherapy in EOC.

Molecular and genetic aspects of DiGeorge/velocardiofacial syndrome.

Cytogenetic, molecular, and clinical genetic studies have contributed to our understanding of the etiology, pathogenesis, and natural history of DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS). Submicroscopic deletions of chromosome 22ql 1.2 are the leading cause of both of these disorders. The 22q 11.2 deletion syndrome is recognized as one of the most common microdeletion syndromes. The clini'cal features are highly variable and include a variety of congenital anomalies, medical problems, and cognitive and neuropsychological difficulties. Infrequently, other chromosomal rearrangements are found in patients with DGS/VCFS, and, rarely, point mutations in the gene TBX1, a transcription factor, that maps to the deleted region. The most sensitive and widely used diagnostic test for detecting the 22ql 1.2 deletion is fluorescence in situ hybridization using probes from the commonly deleted region. Alternatively, polymerase chain reaction can be performed to confirm failure to inherit a parental allele in the region or to determine copy number. Prenatal diagnosis is also available, particularly when a conotruncal cardiac defect is identified during a pregnancy or when a parent carries a deletion. Genetic counseling is recommended before testing to review the natural history of the disorder, testing options, and test sensitivity and limitations.