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1.
Cureus ; 16(4): e58947, 2024 Apr.
Article En | MEDLINE | ID: mdl-38800214

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) outcomes in small centers are commonly considered less favorable than in large-volume centers. New ECMO protocols and procedures were established in our regional community hospital system as part of a cardiogenic shock initiative. This retrospective study aims to evaluate the outcomes of veno-arterial extracorporeal membrane oxygenation (VA ECMO) and extracorporeal cardiopulmonary resuscitation (ECPR) in a community hospital system with cardiac surgery capability and assess whether protocol optimization and cannulation standards result in comparable outcomes to larger centers whether the outcomes of this new ECMO program at the community hospital setting were comparable to the United States averages. METHODS: Our regional system comprises five hospitals with 1500 beds covering southwestern New Jersey, with only one of these hospitals having cardiac surgery and ECMO capability. In May 2021, the new ECMO program was initiated. Patients were screened by a multidisciplinary call, cannulated by our ECMO team, and subsequently treated by the designated team. We reviewed our cardiac ECMO outcomes over two years, from May 2021 to April 2023, in patients who required ECMO due to cardiogenic shock or as a part of extracorporeal cardiopulmonary resuscitation (ECPR). RESULTS: A total of 60 patients underwent cardiac ECMO, and all were VA ECMO, including 18 (30%) patients who required ECPR for cardiac arrest. The overall survival rate for our cardiac ECMO program turned out to be 48% (29/60), with 50% (22/42) in VA ECMO excluding ECPR and 39% (7/18) in the ECPR group. The hospital survival rate for the VA ECMO and ECPR groups was 36% (15/42) and 28% (5/18), respectively. The ELSO-reported national average for hospital survival is 48% for VA ECMO and 30% for ECPR. Considering these benchmarks, the hospital survival rate of our program did not significantly lag behind the national average. CONCLUSIONS: With protocol, cannulation standards, and ECMO management optimized, the VA ECMO results of a community hospital system with cardiac surgery capability were not inferior to those of larger centers.

2.
J Adv Nurs ; 2024 May 13.
Article En | MEDLINE | ID: mdl-38738588

AIMS: To describe the process of breastfeeding relationships among stay-at-home mother and infant dyads at 1, 3, 5 and 6 months. DESIGN: A longitudinal qualitative online survey design was used. METHODS: Data were obtained at 1, 3, 5 and 6 months from 26 breastfeeding mothers who stayed home with their infants and directly breastfed at least once a day for the first 6 months between June 2022 and August 2023. Mothers' written responses to 3 open-ended questions were analysed to assess breastfeeding experiences at home, thoughts/comments while directly breastfeeding and breastfeeding concerns/problems and strategies they used. Based on grounded theory, inductive content analysis was used to analyse the data. Trustworthiness of results was established by coding to consensus, formal peer debriefing and maintaining an audit trail. RESULTS: 'Breastfeeding Relationships at Home,' the core construct, was identified and organized the process of breastfeeding relationships into 5 domains: (1) mothers' emotional well-being while breastfeeding, (2) infant-led feeding, (3) alternatives to breastfeeding, (4) evaluation of breastfeeding and (5) changes in breastfeeding as infants grow older. CONCLUSION: Breastfeeding is not simply about feeding breast milk but also involves nurturing and developing a relationship between mother and infant. Across the domains, mutual responsiveness, a central element of the breastfeeding relationship was clear. Mothers who were committed to breastfeeding with embedded infant suckling reached emotional well-being in return for their engagement which has potential to reduce maternal stress and prevent postpartum depression. IMPACT: Findings from the current study add to nurses' knowledge about the relationship building process between stay-at-home mothers and their infants in the first 6 months of breastfeeding during the COVID-19 pandemic. Nurses must remain sensitive to aid the development of breastfeeding relationships in the home environment to maximize mutual responsiveness. PATIENT OR PUBLIC CONTRIBUTION: No patients or public involved.

3.
Health Promot Pract ; : 15248399241245055, 2024 Apr 08.
Article En | MEDLINE | ID: mdl-38590221

While physical activity (PA) is a strong protective factor for adolescents, many youth experience discrimination and intimidation in traditional fitness spaces. This is especially true for youth of color, youth in larger bodies, and transgender youth. This manuscript describes the development of Move and Thrive, an online resource for PA promotion designed specifically for adolescents prioritizing inclusivity and diversity. Working with Community and Youth Advisory Boards, we developed guiding principles of Move and Thrive: to create resources that are 1) youth and community driven; 2) inclusive of diverse representation; 3) body and weight neutral; 4) trauma informed; and 5) accessible. We developed a guide for PA instructors to use trauma informed approaches; avoid mention of weight talk or physical appearance; use gender inclusive language; and offer multiple options to improve accessibility. Specific care was taken to hire instructors diverse in body size, race, ethnicity, and gender identity. The first iteration of Move and Thrive was launched in March 2021, and the current resource contains 72 PA videos. Over the course of 12 months, the site had more than the site had over 9,000 views in over 40 countries, including six continents. Users have reported high levels of satisfaction with Move and Thrive, and physicians have responded enthusiastically to sharing Move and Thrive as a free resource for adolescents. University of Minnesota Move and Thrive Project is currently available on an ad-free YouTube Channel. We believe that Move and Thrive has the potential to reach populations historically excluded from PA resources.

5.
Orphanet J Rare Dis ; 19(1): 86, 2024 Feb 25.
Article En | MEDLINE | ID: mdl-38403586

BACKGROUND: The Rare Pediatric Disease (RPD) Priority Review Voucher (PRV) Program was enacted in 2012 to support the development of new products for children. Prior to requesting a voucher, applicants can request RPD designation, which confirms their product treats or prevents a rare disease in which the serious manifestations primarily affect children. This study describes the trends and characteristics of these designations. Details of RPD designations are not publicly disclosable; this research represents the first analysis of the RPD designation component of the program. RESULTS: We used an internal US Food and Drug Administration database to analyze all RPD designations between 2013 and 2022. Multiple characteristics were analyzed, including the diseases targeted by RPD designation, whether the product targeted a neonatal disease, product type (drug/biologic), and the level of evidence (preclinical/clinical) to support designation. There were 569 RPD designations during the study period. The top therapeutic areas were neurology (26%, n = 149), metabolism (23%, n = 131), oncology (18%, n = 105). The top diseases targeted by RPD designation were Duchenne muscular dystrophy, neuroblastoma, and sickle cell disease. Neonatology products represented 6% (n = 33), over half were for drug products and 38% were supported by clinical data. CONCLUSIONS: The RPD PRV program was created to encourage development of new products for children. The results of this study establish that a wide range of diseases have seen development-from rare pediatric cancers to rare genetic disorders. Continued support of product development for children with rare diseases is needed to find treatments for all children with unmet needs.


Neoplasms , Rare Diseases , Child , Humans , Infant, Newborn , Drug Approval , Drug Development , Neoplasms/drug therapy , Orphan Drug Production , Rare Diseases/drug therapy , United States , United States Food and Drug Administration
6.
Nurse Educ Today ; 134: 106088, 2024 Mar.
Article En | MEDLINE | ID: mdl-38183906

BACKGROUND: A signature pedagogy is a unique approach that provides a blueprint for curricular decision-making, as it reflects how we teach (surface structures), why we teach (deep structures), and what we believe are vital concepts or values all learners should embody (implicit structures). OBJECTIVE: To investigate what is known from the existing literature about a signature pedagogy to support undergraduate nursing education. DESIGN: This scoping review adopted Arksey and O'Malley's framework to guide the analysis of data. Two electronic databases were used to explore studies on educational strategies, content, and values published in Arabic, English, Filipino, French, Portuguese, and Spanish between 1972 and 2022. RESULTS: A total of 258 articles were included in this review. The analysis revealed that the majority of articles were at the surface (n = 189), followed by the deep (n = 123), with the least number examining the implicit level (n = 90) associated with signature pedagogy levels. Results reflect a limited focus on implicit level; the core concepts and values that all learners should understand and grasp for their future practice to construct their professional identity and engage in healthcare transformation. CONCLUSIONS: The findings from this scoping review, should not be an isolated movement within nursing education. The first step is to engage in discourse amongst all stakeholders, educational and healthcare nurse leaders, regarding the state of the profession. As a profession we need to understand what is the preferred future of nursing and what are the necessary educational processes to ensure the profession is actualizing their mandate. A call to action to develop a unique signature pedagogy should provide synergy between education and practice to enhance learner's competencies as a future professional.


Education, Nursing, Baccalaureate , Education, Nursing , Students, Nursing , Humans , Education, Nursing, Baccalaureate/methods , Education, Nursing/methods , Curriculum , Delivery of Health Care
7.
Health Aff (Millwood) ; 43(1): 18-26, 2024 Jan.
Article En | MEDLINE | ID: mdl-38190603

The Orphan Drug Act of 1983 was enacted to provide financial incentives to stimulate drug development for rare diseases. In recent years, concerns have been raised regarding these orphan drugs, including how many are being approved for both rare and common diseases and the number of subsequent indication approvals. Policy makers have suggested modifications to the Orphan Drug Act's incentives to address these concerns. In this study we investigated the approval "family trees" of orphan drugs. We found that 491 novel orphan drugs were approved between 1990 and 2022. To date, 65 percent have been approved for a single rare disease, 15 percent have been approved for multiple rare diseases, and 20 percent have been approved for both rare and common diseases. Ten percent of orphan drugs received a subsequent indication approval for a pediatric population of an orphan disease. Revenue estimates from 2021 show that one-third of the drugs approved for both rare and common indications and 6 percent of rare-only drugs were among the 200 top-selling drugs worldwide. The results have implications for the possible externalities of modifying the incentives of the Orphan Drug Act, such as a potential decrease in the initiation of programs to develop pediatric rare disease drugs.


Orphan Drug Production , Rare Diseases , Child , Humans , Rare Diseases/drug therapy , Administrative Personnel , Cognition , Drug Development
9.
Patient ; 17(1): 25-37, 2024 Jan.
Article En | MEDLINE | ID: mdl-37833521

BACKGROUND: Rare diseases are estimated to affect more than one in ten Americans. However, most patients with a rare disease face significant emotional, physical, and social challenges. To better understand the burden of disease and unmet needs, the US Food and Drug Administration (FDA) conducts and supports multiple patient engagement platforms. We analyzed summaries from these discussions to identify commonalities among patients with disparate rare diseases, the results of which could inform priorities for cross-disease policies and medical product development. METHODS: We conducted a qualitative analysis of patient engagement session summaries to investigate shared experiences across rare diseases. Cross-disease similarities were identified within four dimensions: product development/regulatory, clinical/physical, social/psychological, and economic/financial. Summaries from 29 rare diseases were included in our analyses. RESULTS: Within the product development/regulatory dimension, we observed that patients and caregivers across rare diseases shared the desire for development of medical products that cured their disease or improved their overall quality of life. In the clinical/physical dimension, we found that patients had numerous common symptoms, including pain and fatigue. In the social/psychological dimension, we observed significant negative impact on mental health. Within the economic/financial dimension, patients and caregivers shared that disease burden caused significant financial hardships. CONCLUSION: We found remarkable similarities among patients with rare diseases across all four dimensions. Our results indicate that, even among rare diseases with diverse etiologies, patients share numerous commonalties due to their diseases: a lack of effective treatment options, certain physical symptoms, mental health challenges, and financial concerns.


Quality of Life , Rare Diseases , Humans , United States , Rare Diseases/psychology , Quality of Life/psychology , Patient Participation , United States Food and Drug Administration , Cost of Illness
10.
Article En | MEDLINE | ID: mdl-37908633

Rifampin is an effective and widely used for the treatment of both active and latent tuberculosis. Although significant side effects are rare, severe side effects such as acute renal failure have been reported in the literature, usually secondary to acute interstitial nephritis. We report a case of rifampin-induced acute renal failure due to heme pigment-related injury in a patient who was receiving daily rifampin as therapy for latent tuberculosis. The patient case illustrates considering rifampin as a potential cause of acute renal failure when no other cause is identified.

12.
bioRxiv ; 2023 Sep 02.
Article En | MEDLINE | ID: mdl-37693566

Assessing fertilized human embryos is crucial for in vitro-fertilization (IVF), a task being revolutionized by artificial intelligence and deep learning. Existing models used for embryo quality assessment and chromosomal abnormality (ploidy) detection could be significantly improved by effectively utilizing time-lapse imaging to identify critical developmental time points for maximizing prediction accuracy. Addressing this, we developed and compared various embryo ploidy status prediction models across distinct embryo development stages. We present BELA (Blastocyst Evaluation Learning Algorithm), a state-of-the-art ploidy prediction model surpassing previous image- and video-based models, without necessitating subjective input from embryologists. BELA uses multitask learning to predict quality scores that are used downstream to predict ploidy status. By achieving an AUC of 0.76 for discriminating between euploidy and aneuploidy embryos on the Weill Cornell dataset, BELA matches the performance of models trained on embryologists' manual scores. While not a replacement for preimplantation genetic testing for aneuploidy (PGT-A), BELA exemplifies how such models can streamline the embryo evaluation process, reducing time and effort required by embryologists.

13.
Orphanet J Rare Dis ; 18(1): 163, 2023 Jun 23.
Article En | MEDLINE | ID: mdl-37353796

BACKGROUND: Rare diseases affect more than 30 million Americans. The passage of the Orphan Drug Act (ODA) in the United States in 1983 represented a launching point for a rare disease drug development revolution for these patients. Financial incentives provided by the ODA through its Orphan Drug Designation Program, in addition to remarkable scientific advances over the past 40 years, have led to hundreds of drug approvals for rare diseases. Our research examines the rare diseases that have been targeted by orphan drug designations and subsequent approvals since the law was enacted. METHODS: Using an internal FDA database, we classified and analyzed all orphan drug designations and approvals from 1983 to 2022 by disease and therapeutic area. RESULTS: Over the 40 years of the ODA, 6,340 orphan drug designations were granted, representing drug development for 1,079 rare diseases. Additionally, 882 of those designations resulted in at least one FDA approval for use in 392 rare diseases. Much of this development has been concentrated in oncology as seven of the top ten most designated and approved diseases were rare cancers. CONCLUSIONS: Researchers have estimated that there may be 7000-10,000 rare diseases that have been identified and described. Based on our study, we can conclude that around 5% of rare diseases have an FDA-approved drug and up to 15% of rare diseases have at least one drug that has been developed and shown promise in their treatment, diagnosis or prevention. Funding of basic and translational science for rare disease drug development should continue in order to bring therapies to the millions of affected patients who remain without treatment options.


Neoplasms , Orphan Drug Production , Humans , United States , Rare Diseases/drug therapy , United States Food and Drug Administration , Drug Approval , Neoplasms/drug therapy
14.
Front Physiol ; 14: 1198615, 2023.
Article En | MEDLINE | ID: mdl-37304825

Introduction: Age-related changes in cerebral hemodynamics are controversial and discrepancies may be due to experimental techniques. As such, the purpose of this study was to compare cerebral hemodynamics measurements of the middle cerebral artery (MCA) between transcranial Doppler ultrasound (TCD) and four-dimensional flow MRI (4D flow MRI). Methods: Twenty young (25 ± 3 years) and 19 older (62 ± 6 years) participants underwent two randomized study visits to evaluate hemodynamics at baseline (normocapnia) and in response to stepped hypercapnia (4% CO2, and 6% CO2) using TCD and 4D flow MRI. Cerebral hemodynamic measures included MCA velocity, MCA flow, cerebral pulsatility index (PI) and cerebrovascular reactivity to hypercapnia. MCA flow was only assessed using 4D flow MRI. Results: MCA velocity between the TCD and 4D flow MRI methods was positively correlated across the normocapnia and hypercapnia conditions (r = 0.262; p = 0.004). Additionally, cerebral PI was significantly correlated between TCD and 4D flow MRI across the conditions (r = 0.236; p = 0.010). However, there was no significant association between MCA velocity using TCD and MCA flow using 4D flow MRI across the conditions (r = 0.079; p = 0.397). When age-associated differences in cerebrovascular reactivity using conductance were compared using both methodologies, cerebrovascular reactivity was greater in young adults compared to older adults when using 4D flow MRI (2.11 ± 1.68 mL/min/mmHg/mmHg vs. 0.78 ± 1.68 mL/min/mmHg/mmHg; p = 0.019), but not with TCD (0.88 ± 1.01 cm/s/mmHg/mmHg vs. 0.68 ± 0.94 cm/s/mmHg/mmHg; p = 0.513). Conclusion: Our results demonstrated good agreement between the methods at measuring MCA velocity during normocapnia and in response to hypercapnia, but MCA velocity and MCA flow were not related. In addition, measurements using 4D flow MRI revealed effects of aging on cerebral hemodynamics that were not apparent using TCD.

15.
Exp Physiol ; 108(8): 1047-1056, 2023 Aug.
Article En | MEDLINE | ID: mdl-37170828

NEW FINDINGS: What is the central question of this study? What is the relationship between prostacyclin and cerebrovascular reactivity to hypercapnia before and after administration of a cyclooxygenase inhibitor, indomethacin, in healthy young and older adults? What is the main finding and importance? Serum prostacyclin was not related to cerebrovascular reactivity to hypercapnia before or after administration of indomethacin. However, in older adults, serum prostacyclin was related to the magnitude of change in cerebrovascular reactivity from before to after indomethacin administration. This suggests that older adults with higher serum prostacyclin may rely more on cyclooxygenase products to mediate cerebrovascular reactivity. ABSTRACT: Platelet activation may contribute to age-related cerebrovascular dysfunction by interacting with the endothelial cells that regulate the response to vasodilatory stimuli. This study evaluated the relationship between a platelet inhibitor, prostacyclin, and cerebrovascular reactivity (CVR) in healthy young (n = 35; 25 ± 4 years; 17 women, 18 men) and older (n = 12; 62 ± 2 years; 8 women, 4 men) adults, who were not daily aspirin users, before and after cyclooxygenase inhibition. Prostacyclin was determined by levels of 6-keto-prostaglandin F1α (6-keto PGF1α) in the blood. CVR was assessed by measuring the middle cerebral artery blood velocity response to hypercapnia using transcranial Doppler ultrasound before (CON) and 90 min after cyclooxygenase inhibition with indomethacin (INDO). In young adults, there were no associations between prostacyclin and middle cerebral artery CVR during CON (r = -0.14, P = 0.415) or INDO (r = 0.27, P = 0.118). In older adults, associations between prostacyclin and middle cerebral artery CVR during CON (r = 0.53, P = 0.075) or INDO (r = -0.45, P = 0.136) did not reach the threshold for significance. We also evaluated the relationship between prostacyclin and the change in CVR between conditions (ΔCVR). We found no association between ΔCVR and prostacyclin in young adults (r = 0.27, P = 0.110); however, in older adults, those with higher baseline prostacyclin levels demonstrated significantly greater ΔCVR (r = -0.74, P = 0.005). In conclusion, older adults with higher serum prostacyclin, a platelet inhibitor, may rely more on cyclooxygenase products for cerebrovascular reactivity to hypercapnia.


Epoprostenol , Hypercapnia , Male , Young Adult , Humans , Female , Aged , Epoprostenol/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Prostaglandin-Endoperoxide Synthases , Endothelial Cells , Indomethacin/pharmacology , Prostaglandins I/pharmacology , Cerebrovascular Circulation/physiology , Blood Flow Velocity/physiology , Carbon Dioxide
16.
J Econ Entomol ; 116(3): 823-834, 2023 06 13.
Article En | MEDLINE | ID: mdl-37178157

Nearly all maize seed sold in the United States includes a neonicotinoid seed treatment (NST), meant to protect seedlings against early-season insect pests. For key pests, including western corn rootworm (Diabrotica virgifera virgifera LeConte) (D.v.v), insecticidal proteins derived from Bacillus thuringiensis (Bt) are expressed in plant tissues as alternatives to soil-applied insecticides. Insect resistance management (IRM) plans use non-Bt "refuges" to encourage survival of Bt-susceptible D.v.v., which maintains susceptible alleles in the population. In non-cotton producing regions, IRM guidelines require a minimum 5% blended refuge for maize expressing more than 1 trait targeting D.v.v. Prior work has shown that 5% blends yield insufficient proportions of refuge beetles to contribute reliably to IRM. Whether NSTs interfere with survivorship of refuge beetles is unknown. Our objective was to determine whether NSTs affect proportions of refuge beetles, and secondarily, to determine whether NSTs provide agronomic advantages over Bt seed alone. To reveal host plant type (i.e., Bt or refuge), we used a stable isotope (15N) to mark refuge plants in plots with 5% seed blends. To assess refuge performance between treatments, we compared proportions of beetles from respective natal hosts. In all site-years, NSTs showed inconsistent effects on proportions of refuge beetles. Treatment comparisons showed inconsistent agronomic benefits of NSTs when combined with Bt traits. Our results demonstrate that NSTs have a negligible impact on refuge performance and reinforces the assertion that 5% blends are serving little benefit for IRM. Plant stand and yield were not improved by NSTs.


Bacillus thuringiensis , Coleoptera , Insecticides , Animals , Zea mays/genetics , Neonicotinoids , Crop Protection , Plants, Genetically Modified/genetics , Bacterial Proteins/genetics , Endotoxins , Hemolysin Proteins/genetics , Insecticides/pharmacology , Bacillus thuringiensis/genetics , Seeds , Insecticide Resistance , Larva
17.
Curr Opin HIV AIDS ; 18(3): 119-125, 2023 05 01.
Article En | MEDLINE | ID: mdl-37144613

PURPOSE OF REVIEW: We review the intersection between the HIV and COVID-19 pandemics, particularly the impact of HIV infection on the development of severe COVID-19. RECENT FINDINGS: Studies early in the COVID-19 pandemic did not find a clear link between HIV infection and increased COVID-19 severity or mortality. People with HIV (PWH) were more likely to have severe COVID-19, but much of the risk for worse outcomes was related to high rates of comorbidities and social determinants of health. Although comorbidities and social determinants of health are certainly critically important reasons for severe COVID-19 among PWH, recent large studies have found HIV infection - particularly when the CD4 cell count is low or HIV RNA is not suppressed - is an independent risk factor for COVID-19 severity. The link between HIV and severe COVID-19 highlights the need to diagnose and treat HIV as well as the importance of COVID-19 vaccination and treatment among PWH. SUMMARY: People with HIV have faced increased challenges during the COVID-19 pandemic because of high rates of comorbidities and social determinants of health as well as the impact of HIV on COVID-19 severity. Information on the intersection of the two pandemics has been crucial to improving care for people with HIV.


COVID-19 , HIV Infections , Humans , HIV Infections/complications , COVID-19/epidemiology , COVID-19 Vaccines , Pandemics , Risk Factors
18.
Contemp Clin Trials ; 129: 107198, 2023 06.
Article En | MEDLINE | ID: mdl-37068589

BACKGROUND: Since 1983, the Orphan Product Grants Program, administered by the US Food and Drug Administration, provides funding for clinical trials and natural history studies in rare diseases. The COVID-19 pandemic created new challenges in rare disease product development. This study sought to determine the effects of the pandemic on rare disease studies using data from grantees of this program, and determine lessons learned that can potentially be applied to future trials in rare diseases. METHODS: All grants that were being funded by the Orphan Products Grants Program between March 2020 and March 2021 were included in the study. Data was gathered from grantees and described the effects of the pandemic on multiple aspects of the studies including enrollment, patient follow-up, protocol, and budget. RESULTS: There were 62 grants active during the study period, and of these 54 (87%) were clinical trials and 8 (13%) were natural history studies. 94% of the grantees reported their studies being affected by the COVID-19 pandemic, and the addition of virtual capabilities was reported by 34 (55%) of grantees. CONCLUSIONS: This study suggested two important lessons learned. First, virtual capabilities, when appropriate, can be an important component of trials because they decrease the travel burden on participants and reduce in-person risks, which should increase patient recruitment and retention. Second, building in flexibility in clinical trials is critical in the post-COVID era and could include increasing the use of multi-site trials, clinical networks, and innovative designs and collaborations to speed up trials without compromising study data.


COVID-19 , Humans , Pandemics , Patient Selection , Rare Diseases/drug therapy , Rare Diseases/epidemiology , United States/epidemiology , United States Food and Drug Administration , Clinical Trials as Topic
19.
Am J Hum Genet ; 110(4): 565-574, 2023 04 06.
Article En | MEDLINE | ID: mdl-36977411

Preimplantation genetic testing commonly employs simplistic copy-number analyses to screen for aneuploidy in blastocyst trophectoderm biopsies. Interpreting intermediate copy number alone as evidence of mosaicism has led to suboptimal estimation of its prevalence. Because mosaicism originates from mitotic nondisjunction, utilizing SNP microarray technology to identify the cell-division origins of aneuploidy might provide a more accurate estimation of its prevalence. The present study develops and validates a method of determining the cell-division origin of aneuploidy in the human blastocyst by using both genotyping and copy-number data in parallel. The concordance of predicted origins with expected results was demonstrated in a series of truth models (99%-100%). This included determination of X chromosome origins from a subset of normal male embryos, determination of the origins of translocation chromosome-related imbalances via embryos from couples with structural rearrangements, and prediction of either mitotic or meiotic origins via multiple rebiopsies of embryos with aneuploidy. In a cohort of blastocysts with parental DNA (n = 2,277), 71% were euploid, 27% were meiotic aneuploid, and 2% were mitotic aneuploid, indicating a low frequency of bona fide mosaicism in the human blastocyst (mean maternal age: 34.4). Chromosome-specific trisomies in the blastocyst were also consistent with observations previously established in products of conception. The ability to accurately identify mitotic-origin aneuploidy in the blastocyst could benefit and better inform individuals whose IVF cycle results in all aneuploid embryos. Clinical trials with this methodology might also help provide a definitive answer regarding the reproductive potential of bona fide mosaic embryos.


Preimplantation Diagnosis , Pregnancy , Female , Humans , Male , Adult , Preimplantation Diagnosis/methods , Blastocyst , Aneuploidy , Genetic Testing/methods , Mosaicism
20.
LGBT Health ; 10(3): 220-227, 2023 04.
Article En | MEDLINE | ID: mdl-36796003

Purpose: Latine transgender/gender diverse (TGD) adolescents may be at increased risk of emotional distress due to structural oppression affecting their intersecting nondominant identities. Multiple protective factors may buffer emotional distress among Latine TGD adolescents. We studied how these protective factors relate to emotional distress, comparing Latine with non-Latine TGD students. Methods: We conducted a cross-sectional analysis of the 2019 Minnesota Student Survey, which included 3861 TGD and gender questioning (GQ) youth (10.9% Latine) in grades 8, 9, and 11 across Minnesota. We used multiple logistic regression with interaction terms to examine associations between protective factors (school connectedness, family connectedness, and internal assets) and emotional distress (depressive symptoms, anxiety symptoms, self-harm, suicidal ideation, and suicide attempt) between Latine TGD/GQ students and non-Latine TGD/GQ students. Results: There was a significantly higher rate of suicide attempts in Latine TGD/GQ students (36.2%) compared with non-Latine TGD/GQ students (26.3%, χ2 = 15.53, p < 0.001). In unadjusted models, school connectedness, family connectedness, and internal assets were associated with lower odds of all five indicators of emotional distress. In fully adjusted models, family connectedness and internal assets remained associated with significantly lower odds of all five indicators of emotional distress; these protective associations were similar across all TGD/GQ students regardless of Latine identity. Conclusion: Higher rates of suicide attempts in Latine TGD/GQ youth emphasize the need to better understand protective factors in youth with multiple nondominant social identities and identify programming that supports well-being. Family connectedness and internal assets can protect against emotional distress among both Latine and non-Latine TGD/GQ youth.


Psychological Distress , Transgender Persons , Humans , Adolescent , Protective Factors , Cross-Sectional Studies , Suicide, Attempted
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