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Background: Patients with chronic intestinal failure (CIF) may be predisposed to poor oral health outcomes. This study explored the self-reported oral health status, function, and psychological impacts of oral health of adult patients with CIF, their access to dental care, and how these compare with the broader population., Methods: All patients >18 years old receiving home intravenous therapies for CIF were invited to complete a self-reported questionnaire providing information on oral health status and access to oral health services. Collateral information was provided by treating clinicians. Descriptive data analysis was undertaken, including subgroup analysis of clinical characteristics, and was compared with the available population-level data., Results: Twenty-four patients participated. Short gut and dysmotility accounted for 88% of the etiologies of CIF. Respondents reported good preventative oral health behaviors (96%), accessing dental care within the last 12 months (75%), and limited barriers to receiving care. Dry mouth (96%), oral pain (59%), and temperature sensitivity (60%) were commonly reported across the cohort. Smoking history and reduced oral diet were associated with significantly worse self-reported oral health outcomes. Patients with CIF reported worse oral health outcomes despites better oral health access than the general population., Conclusion: Patients with CIF appear to be at risk of poor oral health outcomes, especially where smoking or reduced oral intake are concurrently involved. Clinicians involved in CIF care should be alert to the oral health needs of this population and consider oral and dental health as part of the multidisciplinary care required for optimal CIF care., (© 2024 American Society for Parenteral and Enteral Nutrition.)

Objective: We have previously demonstrated that maternal-plasma cell-free DNA (cfDNA)-testing can detect chromosomal anomalies in recurrent pregnancy loss (RPL) with 81.8% sensitivity and 90.3% specificity. Here we assess whether this is cost effective in guiding further workup in RPLs., Method: A decision-analytic model was developed to compare the cost of various RPL management pathways: (1) current American Society for Reproductive Medicine (ASRM) RPL workup; (2) microarray or karyotyping analysis of products of conception (POCs) and RPL workup only for euploid cases; and (3) cfDNA testing and RPL workup only for euploid cases. Sample accessibility, failure rates, and sensitivity were specified for each test. Costs of sample collection, genetic tests, and RPL workup were considered. Analysis outcomes included detection rate of chromosomal anomaly and cost per patient tested., Results: In comparison to existing cytogenetic testing on POCs, cfDNA testing pathway allowed for better sample accessibility with a lower cost per patient. In addition, using cfDNA to guide further workup significantly increases the number of causative fetal chromosome anomalies detected, reducing the number of patients undergoing unnecessary workup resulting in an overall cost savings., Conclusion: Our study showed that inclusion of cfDNA testing is a cost-effective approach to guide RPL workup., (© 2021 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

About 30% of the world population is infected with Mycobacterium tuberculosis (MTB). It is well known that the gene expression in MTB is highly variable, thus screening of traditional single-gene in MTB has been incapable to meet the desires of clinical diagnosis. In this report, the authors systemically analysed the transcription regulatory network (TRN) in MTB H37Rv. The complex interplay of these gene interactions has been revealed using exhaustive topological and global analysis of TRN using parameters including indegree, outdegree, degree, directed and undirected average path length (APL), and randomly performed. Results from indegree analysis reveal a set of important genes, including papA5 and Rv0177 which are associated with high indegree values. Gene ontology analysis suggested their importance in the virulence of MTB. In addition, APL and analysis of highly significant genes further identified some critical genes with different APL values. Among the list of genes identified, the csoR gene has the shortest directed APL score and high outdegree value, thus suggesting their importance in maintaining network topology. This study provides a comprehensive analysis of TRN and offers a good basis of understanding for developing experimental study in search of new therapeutic targets against MTB H37Rv pathogen.

Background: Patients with advanced cancer and their caregivers have substantial misperceptions regarding hospice, which contributes to its underuse., Methods: The authors conducted a single-site randomized trial of a video educational tool versus a verbal description of hospice in 150 hospitalized patients with advanced cancer and their caregivers. Patients without a caregiver were eligible. Intervention participants (75 patients and 18 caregivers) viewed a 6-minute video depicting hospice. Control participants (75 patients and 26 caregivers) received a verbal description identical to the video narrative. The primary outcome was patient preference for hospice. Secondary outcomes included patient and/or caregiver knowledge and perceptions of hospice, and hospice use., Results: Between February 2017 and January 2019, approximately 55.7% of eligible patients (150 of 269 eligible patients) and 44 caregivers were enrolled. After the intervention, there was no difference noted with regard to patients' preferences for hospice (86.7% vs 82.7%; P = .651). Patients in the video group reported greater knowledge regarding hospice (9.0 vs 8.4; P = .049) and were less likely to endorse that hospice is only about death (6.7% vs 21.6%; P = .010). Among deceased patients, those assigned to the intervention were more likely to have used hospice (85.2% vs 63.6%; P = .01) and to have had a longer hospice length of stay (median, 12 days vs 3 days; P < .001). After the intervention, caregivers assigned to view the video were more likely to prefer hospice for their loved ones (94.4% vs 65.4%; P = .031), reported greater knowledge concerning hospice (9.7% vs 8.0%; P = .001), and were less likely to endorse that hospice is only about death (0.0% vs 23.1%; P = .066)., Conclusions: A hospice video did not significantly impact patients' preferences for hospice care. Patients with advanced cancer and their caregivers who were assigned to view the video were more informed regarding hospice and reported more favorable perceptions of hospice. Patients were more likely to use hospice and to have a longer hospice length of stay., (© 2020 American Cancer Society.)

We designed and implemented a novel automated negative non-invasive prenatal test (NIPT) result disclosure process using a proprietary, HIPAA-compliant web-based portal. High-risk pregnant patients who opted for NIPT from 04/2017 to 12/2018 were given the option to receive their negative result through the automated process. Patients were required to watch a brief educational video and answer evaluative questions before downloading their result. After completing the process, patients completed a survey regarding their opinion of the efficiency and convenience of the process and their satisfaction. A total of 10,170 women registered online during the study period, and 8,965 completed the automated process (88%). Out of 8,965 women, 2,121 women responded to the survey (24%). Most (2,030 of 2,101) strongly agreed/agreed that they could easily navigate the patient portal (97%); 1,852 of 1,966 strongly agreed/agreed that disclosure was efficient and convenient (94%); 1,852 of 1,960 strongly agreed/agreed that they felt informed after watching a short educational video (94%); and 1,903 of 1,967 strongly agreed/agreed that they preferred downloading results rather than waiting for their next doctor's appointment (97%). This study demonstrates high patient satisfaction with this automated and scalable solution in a high-volume health system. As the utilization of genetic testing increases, we predict greater need for innovative healthcare delivery models., (© 2019 Metis Genetics. Journal of Genetic Counseling published by Wiley Periodicals, Inc. on behalf of the National Society of Genetic Counselors.)

Purpose: Fluorescence lifetime imaging microscopy (FLIM) of endogenous fluorescent metabolites permits the measurement of cellular metabolism in cell, tissue and animal models. In parallel, magnetic resonance spectroscopy (MRS) of dynamic nuclear (hyper)polarized (DNP) 13 C-pyruvate enables measurement of metabolism at larger in vivo scales. Presented here are the design and initial application of a bioreactor that connects these 2 metabolic imaging modalities in vitro, using 3D cell cultures., Methods: The model fitting for FLIM data analysis and the theory behind a model for the diffusion of pyruvate into a collagen gel are detailed. The device is MRI-compatible, including an optical window, a temperature control system and an injection port for the introduction of contrast agents. Three-dimensional printing, computer numerical control machining and laser cutting were used to fabricate custom parts., Results: Performance of the bioreactor is demonstrated for 4 T1 murine breast cancer cells under glucose deprivation. Mean nicotinamide adenine dinucleotide (NADH) fluorescence lifetimes were 10% longer and hyperpolarized 13 C lactate:pyruvate (Lac:Pyr) ratios were 60% lower for glucose-deprived 4 T1 cells compared to 4 T1 cells in normal medium. Looking at the individual components of the NADH fluorescent lifetime, τ 1 (free NADH) showed no significant change, while τ 2 (bound NADH) showed a significant increase, suggesting that the increase in mean lifetime was due to a change in bound NADH., Conclusion: A novel bioreactor that is compatible with, and can exploit the benefits of, both FLIM and 13 C MRS in 3D cell cultures for studies of cell metabolism has been designed and applied., (© 2019 International Society for Magnetic Resonance in Medicine.)

Curcumin, a natural diarylheptanoid, is extensively used as a food additive or dietary supplement on the regular basis. It is known to have potential to encumber the drug transporters and hepatic drug metabolizing enzymes that lead to pharmacokinetic interactions with drug or food. Daclatasvir is a new orally acting drug for the treatment of chronic Hepatitis C Virus infections. This is a substrate of P-glycoprotein and CYP3A4 that are involved in the major pharmacokinetic interaction. Hence, the studies' aim is to assess for any possible pharmacokinetic interactions. Pharmacokinetic studies of daclatasvir in presence or absence of curcumin were carried out in Wistar rats following oral administration. Parallelly, the oral pharmacokinetics of daclatasvir was also determined in the presence of ketoconazole or quinidine. Studies revealed that plasma level of daclatasvir was not altered significantly during concomitant single dose administration of curcumin, whereas significantly decreased upon pretreatment for 7 days with curcumin at high dose level. Ketoconazole and quinidine markedly increase daclatasvir exposure following concomitant administration with daclatasvir. It can be concluded that dose adjustment is unlikely to be required for intermittent use of curcumin at low dose but cautious for chronic and concomitant use of curcumin at a high dose., (Copyright © 2018 John Wiley & Sons, Ltd.)

Objectives: To determine the underlying biological basis for noninvasive prenatal testing (NIPT) results of multiple aneuploidies or autosomal monosomies., Methods: Retrospective analysis of 113,415 tests to determine the study cohort, consisting of 138 (0.12%) cases reported as a single autosomal monosomy (n = 65), single trisomy with a sex chromosome aneuploidy (n = 36), or with multiple aneuploidies (n = 37). Clinical outcome information was reviewed and stratified into eight categories according to whether the karyotype or sonographic information agreed or disagreed with sequencing results., Results: Of 67 cases with fetal or neonatal karyotypes available, 16 (24%) were partially or fully concordant with the NIPT result, 4 (6%) had aneuploidy on a reference chromosome, and 47 (70%) had normal fetal chromosomes, in which 5/47 had maternal malignancies reported. One case of maternal mosaic trisomy 8 was also detected. Of cases with no fetal karyotype information, ten had an abnormal clinical outcome, one was a normal live birth, and one reported maternal malignancy., Conclusions: Noninvasive prenatal test results of autosomal monosomy or multiple aneuploidies are rare but have a diversity of underlying biologic causes. Some reflect the fetal karyotype; some reflect the presence of other maternal or fetal chromosome abnormalities, and a small number are linked to maternal disease., (© 2016 Illumina. Prenatal Diagnosis published by John Wiley & Sons, Ltd.)

Objective: The primary goal of this study was to provide clinically relevant information for appropriate patient counseling., Method: Demographics and test metrics were reviewed for 86 658 clinical cases. Outcome information was requested for samples reported as aneuploidy detected or suspected for chromosomes 21, 18, or 13; voluntary outcome reporting was encouraged for all discordant outcomes., Results: Of 86 658 cases, 85 298 (98.4%) met inclusion criteria for result reporting. Of the 1360 (1.6%) cancellations, only 101 (0.1%) were for technical reasons. Average time to result was 3.3 business days. Aneuploidy was detected or suspected in 2142 (2.5%) samples. For aneuploidy detected cases with known clinical outcomes, the overall positive predictive value (PPV) was 83.5% (608/728); observed PPVs for trisomies 21, 18, and 13 ranged from 50.0 to 92.8%. As individual PPVs are determined by a patient's prior risk, we developed a chart for counseling patients on positive predictive value based on maternal age., Conclusion: This large-scale report reinforces that noninvasive prenatal testing is a highly accurate screen for fetal aneuploidy in the general obstetric population. Test improvements have facilitated a reduction in failure rates, time to result, and borderline results/unclassifiable results. We have developed a positive predictive value counseling tool to ensure appropriate patient education, counseling, and clinical utilization., (© 2015 John Wiley & Sons, Ltd.)

Objective: The aim of this study is to report the experience of noninvasive prenatal DNA testing using massively parallel sequencing in an accredited clinical laboratory., Methods: Laboratory information was examined for blood samples received for testing between February and November 2012 for chromosome 21 (Chr21), Chr18, and Chr13. Monosomy X (MX) testing was available from July 2012 for cystic hygroma indication. Outcomes were collected from providers on samples with positive results., Results: There were 5974 samples tested, and results were issued within an average of 5.1 business days. Aneuploidy was detected in 284 (4.8%) samples (155 Chr21, 66 Chr18, 19 Chr13, 40 MX, and four double aneuploidy). Follow-ups are available for 245/284 (86%), and 77/284 (27.1%) are confirmed, including one double-aneuploidy case concordant with cytogenetics from maternal malignancy. Fourteen (0.2%) discordant (putative false-positive) results (one Chr21, six Chr18, three Chr13, three MX, and one Chr21/13) have been identified. Five (0.08%) false-negative cases are reported (two trisomy 21, two trisomy 18, and one MX). In 170 (2.8%) cases, the result for a single chromosome was indefinite., Conclusions: This report suggests that clinical testing of maternal cell-free DNA for fetal aneuploidy operates within performance parameters established in validation studies. Noninvasive prenatal testing is sensitive to biological contributions from placental and maternal sources., (©2013 Verinata Health, Inc. Prenatal Diagnosis published by John Wiley & Sons, Ltd.)

Objective: We evaluated the trends in uptake of amniocentesis and chorionic villi sampling (CVS) for prenatal diagnosis compared with uptake of first and second trimester prenatal serum screening for Down syndrome among patients referred for genetic counseling for advanced maternal age (AMA)., Methods: Patients referred for AMA genetic counseling from 2001 through 2008 were informed of both prenatal serum screening and invasive diagnostic testing options. Testing offered and testing decisions were entered in a computer database and uptake rates calculated for each year with trends compared using logistic regression analysis., Results: From 2001 through 2007, we observed a decline in amniocentesis and CVS uptake (p = 0.0001). This trend reversed in 2008 for both invasive procedures (p = 0.0001). Uptake of prenatal serum screening increased over the study period with uptake of first trimester screening increasing 1.7 fold in 2008., Conclusion: Improved prenatal screening tests and increased availability of screening for AMA patients has led to a steady decline in uptake of invasive testing from 2001 through 2007. This trend reversed from 2007 through 2008. Possible reasons for this reversal are discussed., (Copyright (c) 2010 John Wiley & Sons, Ltd.)

Objective: To evaluate the clinical significance of the supernumerary marker chromosomes (SMCs) detected during prenatal diagnosis., Methods: We retrospectively studied cytogenetic/fluorescence in situ hybridization (FISH) results and clinical evaluation of 110 marker cases identified from approximately 100,000 cases referred for prenatal diagnosis. The clinical follow-up performed was focused on cases with de novo markers not derived from chromosome 15., Results: Among the 110 SMCs, 79 (71.8%) were de novo, 24 (21.8%) were familial, and the origin was undetermined in 7 cases. Fifty-eight of the SMCs originated from nonacrocentric chromosomes and 52 SMCs were derived from acrocentric chromosomes, with 27 originating from chromosome 15. Twenty-two of the SMCs from chromosome 15 did not contain the Prader-Willi/Angelman syndrome critical region, and uniparental disomy was ruled out in 19/19 cases. Clinical information ranging from birth to 4 years was obtained for 46 de novo cases with nonchromosome-15-derived SMCs. Of these cases, 11/11 acrocentric SMCs resulted in normal phenotype. In contrast, 4/23 cases with single nonacrocentric SMCs and 3/5 cases with two or more SMCs resulted in an abnormal phenotype., Conclusions: Our data suggests an overall low risk for acrocentric SMCs and a higher risk for nonacrocentric SMCs. Phenotypes associated with markers derived from some specific chromosomes are also discussed., (2006 John Wiley & Sons, Ltd.)

Results from conventional cytogenetic studies on 21 609 amniotic fluid specimens were analyzed retrospectively to determine the residual risk for a cytogenetic abnormality if interphase FISH, capable of only detecting aneuploidy for chromosomes 13, 18, 21, X and Y, was performed and did not reveal an abnormality. Detection rates (the probability of detecting a cytogenetic abnormality when an abnormality is present) and residual risks (the likelihood of a cytogenetic abnormality, in view of normal interphase FISH results) were calculated for the four major clinical indications for prenatal diagnosis (advanced maternal age, abnormal maternal serum screen indicating increased risk for trisomy 18 or trisomy 21, abnormal maternal serum screen indicating increased risk for neural tube defects and ultrasound abnormality). Differences in detection rates were observed to depend on clinical indication and presence or absence of ultrasound abnormalities. The detection rate ranged from 18.2 to 82.6% depending on the clinical indication. The detection rates of abnormalities significant to the pregnancy being evaluated (i.e. abnormalities excluding familial balanced rearrangements and familial markers) were between 28.6 and 86.4%. The presence of ultrasound abnormalities increased the detection rate from 72.2 to 92.5% for advanced maternal age and from 78.6 to 91.3% for abnormal maternal serum screen, indicating increased risk for trisomy 18 or trisomy 21. With regard to residual risk, the risk for a clinically significant abnormality decreased from 0.9-10.1%, prior to the interphase FISH assay, to a residual risk of 0.6-1.5% following a normal interphase FISH result in the 4 groups studied. Providing patients with detection rates and residual risks, most relevant to their situation (clinical indication and presence or absence of ultrasound abnormality) during counseling, could help them better understand the advantages and limitations of interphase FISH in their prenatal diagnostic evaluation., (Copyright 2003 John Wiley & Sons, Ltd.)

Objectives: Mosaicism involving a 45,X cell line is relatively common in prenatal diagnosis. In prenatally diagnosed cases, the prognosis of non-mosaic 45,X and 45,X/46,XY mosaicism are different. Therefore, accurate identification of a cell line containing Y chromosome is critical for genetic counseling and postnatal management., Methods: We investigated the ultrasound findings and outcomes of pregnancies with a 45,X cell line identified during mid-trimester cytogenetic analysis., Results: A total of 105 cases were found to have a 45,X cell line by standard cytogenetic analysis. Seventy-four cases were found to have non-mosaic 45,X at initial diagnosis. Of these 74 cases, 68 had abnormal ultrasound findings that were characteristic of Turner syndrome. Of the six cases with normal ultrasound findings, ultrasound examination was normal with male genitalia identified in three cases. Thorough cytogenetic and fluorescent in situ hybridization (FISH) analysis identified Y chromosome material in all three cases, one with a dicentric Y;14 chromosome and the other two cases with a marker chromosome containing Sex-determining Region (SRY) material in a small portion of the cells. In contrast, in 31 cases with a mosaic 45,X karyotype, ultrasound abnormality was identified only in one case., Conclusions: The present data suggest the need for follow-up ultrasound examination and thorough cytogenetic and molecular analysis for Y chromosome material in 45,X cases with normal ultrasound findings., (Copyright 2002 John Wiley & Sons, Ltd.)

Mesenchymal chondrosarcoma, an uncommon lesion of bone and extraskeletal tissue, is rare in the orbit. A case of extraskeletal mesenchymal chondrosarcoma of the orbit in a 28-year-old woman presenting with proptosis and diminution of vision in the left eye is reported. Histologically, the tumor showed areas of undifferentiated mesenchymal cells with islands of cartilage. Immunohistochemical analysis for S-100 protein showed focal positivity in chondroid areas. The eye was preserved and the patient has good vision after 2 years of follow-up.