Publications by authors named "Danny Schust"
Article Synopsis
- A study explored the effectiveness of the oral human papillomavirus (HPV) vaccine IGMKK16E7 in treating cervical intraepithelial neoplasia, showing promising results where some patients experienced a complete histological response.
- Researchers analyzed cervix-exfoliated cell samples from 42 patients to identify biomarkers that could predict the success of the vaccine, focusing on various gene expressions related to immune response.
- The key finding was that lower levels of the biomarker CD86 correlated with a higher likelihood of achieving a complete response to the vaccine, with CD86-low patients demonstrating a significantly increased response rate compared to those with higher CD86 levels.
Obstructive sleep apnea in pregnancy: A review of the literature from the obstetrics practitioner's view and a proposed clinical approach.
Eur J Obstet Gynecol Reprod Biol
September 2024
Article Synopsis
- Obstructive sleep apnea (OSA) is common in pregnant women, particularly those who are obese, and can negatively affect both maternal and fetal health, necessitating further research.
- Current diagnostic criteria and screening tools for OSA in pregnancy are limited, hindering effective referrals for diagnosis and treatment by healthcare providers.
- The review aims to enhance screening and management strategies for OSA in pregnancy, ultimately equipping obstetric practitioners to better support and counsel their patients to reduce OSA-related risks.
Ectopic pregnancies are one of the most common causes of obstetric mortality worldwide. Interstitial ectopic pregnancies, defined as an extracavitary pregnancy within the portion of the Fallopian tube that transverses the myometrium, have reported mortality rates approximately seven times higher than all types of ectopic pregnancy combined. In contrast, intracavitary eccentric gestations, often labeled as "cornual" or "angular" pregnancies, have reportedly high rates of live birth.
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- * This review summarizes existing research on LPD, highlights the lack of validated diagnostic criteria, and discusses the controversial role of progesterone supplementation in treating RPL.
- * There's a need for better assessment tools for LPD and further research to understand its impact on fertility and find effective treatments.
Article Synopsis
- Suppressyn is a placental protein that inhibits syncytin-1, revealing complex regulation of cell fusion in the placenta.
- The study identified a promoter and a novel enhancer for suppressyn's gene, both crucial for its tissue-specific expression.
- Regulation of suppressyn expression involves DNA methylation and hypoxia-sensitive transcription factors, which could impact normal and abnormal placental development in conditions like preeclampsia and fetal growth restriction.
Article Synopsis
- A clinical trial tested an oral vaccine, IGMKK16E7, derived from lacticaseibacillus to treat patients with HPV-16-positive cervical lesions, aiming to promote local immune responses as opposed to systemic ones.
- Results showed that among high-dose recipients, 31.7% experienced complete regression of lesions compared to only 12.5% in the placebo group, indicating potential effectiveness of the vaccine.
- The study found no significant difference in adverse effects between high-dose and placebo groups, suggesting that IGMKK16E7 is safe while leading to promising immune responses against HPV-16.
Importance: Prenatal cannabis use is rising and is a major public health issue. Cannabis use in pregnancy and during lactation has been associated with increased maternal and offspring morbidity and mortality.
Objective: This review aims to summarize the existing literature and current recommendations for cannabis use during pregnancy or lactation.
Article Synopsis
- The study investigates the effects of edible cannabis use during pregnancy on the fetal and placental epigenome, particularly focusing on DNA methylation.
- In trials, pregnant rhesus macaques consumed either THC-infused edibles or a placebo, revealing that THC exposure resulted in significant differential methylation at 581 CpG sites, mostly in the placenta.
- The findings suggest that prenatal THC exposure may disrupt gene regulation involved in neurobehavioral development, potentially impacting long-term outcomes for offspring, highlighting the need for better guidance on cannabis use during pregnancy.
Article Synopsis
- The study aimed to assess a new hCG threshold model for classifying pregnancies as viable or nonviable in individuals with unknown pregnancy viability.
- The research analyzed data from a cohort of 688 patients, revealing that the new model accurately identified 100% of viable intrauterine pregnancies while reducing misclassification of early pregnancy losses and ectopic pregnancies.
- Results indicated that the new model decreased incorrect classifications from 24.1% to 12.1% for ectopic pregnancies and from 9.5% to 5.6% for early pregnancy losses over a 6-day period after the initial hCG test.
Article Synopsis
- Substance use rates are increasing among individuals of reproductive age, with important implications for offspring health.
- Emerging research indicates that substance use by both parents before conception and during pregnancy can affect gene expression in their children, potentially leading to issues with neurodevelopment and mental health later in life.
- This review discusses the need for more understanding of these effects, suggesting that targeting public health initiatives and counseling for expectant parents could help reduce health risks for their children.
Article Synopsis
- Career development awards are essential for helping OBGYN physician-scientists gain investigative independence and advance their careers.
- Careful selection of the right funding award, particularly the NIH K-series awards, is crucial for maximizing the chances of success.
- The Reproductive Scientist Development Program (RSDP) serves as a key example of a mentorship-based award that supports OBGYN scientific training and is vital for nurturing future leaders in women’s health.
Article Synopsis
- The placenta protects against harmful substances during pregnancy, and issues with its development can cause serious complications like preeclampsia and preterm birth.
- Researchers previously found that the immune regulator B7-H4/VTCN1 shows increased expression during the early differentiation of human embryonic stem cells into trophoblasts.
- This study examines how B7-H4/VTCN1 affects trophoblast development, antiviral responses, and influences on MHC class I expression and natural killer cell (NK cell) behavior.
Uterine glands and, by inference, their secretions impact uterine receptivity, blastocyst implantation, stromal cell decidualization, and placental development. Changes in gland function across the menstrual cycle are primarily governed by the steroid hormones estrogen (E2) and progesterone (P4) but can also be influenced by extrinsic factors from the stroma. Using a human endometrial epithelial organoid system, transcriptome and proteome analyses identified distinct responses of the organoids to steroid hormones and prostaglandin E2 (PGE2).
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- Suppressyn (SUPYN) is a protein that inhibits cell fusion and is primarily found in the placenta, where it helps regulate cell formation.
- Research indicates that in placentas affected by Down syndrome (TS21), there are changes in SUPYN levels, which correlate with delays in placental cell development and fusion.
- Increased SUPYN levels in both the placenta and maternal serum in Down syndrome pregnancies suggest it could be a potential diagnostic marker for the condition.
Article Synopsis
- Understanding human placentation is crucial for developing treatments for pregnancy complications and has evolved to include animal and human model systems.
- Recent advancements involve using stem cell-derived models that closely mimic placental development, improving insights into both normal and abnormal trophoblast development.
- New RNA-sequencing technologies, especially single nuclei RNA sequencing (snRNA-seq), are being used to study the syncytiotrophoblast, enhancing our understanding of its roles and enabling more focused research on conditions like preeclampsia and intrauterine growth retardation.
Article Synopsis
- There is a notable sex difference in COVID-19 severity, with males generally experiencing worse outcomes, although the reasons for this are not fully understood.
- The study investigates how maternal-fetal interactions related to antibody transfer and interferon responses are influenced by fetal sex in pregnancies affected by SARS-CoV-2.
- Findings reveal that pregnant women with male fetuses display different levels of placental immune responses and antibody transfer, indicating that fetal sex affects maternal immunity to the virus.
Article Synopsis
- Proper placental development depends on regulated trophoblast differentiation and maternal cell interaction, with human endogenous retroviruses (HERVs) playing a key role in cell fusion within trophoblast cells.
- Syncytin-1 (ERVW-1) promotes the fusion of cytotrophoblast (CTB) cells to form the syncytiotrophoblast (STB), while Suppressyn (ERVH48-1) counteracts this fusion through competition for the same receptor.
- Research indicates that HERV expression levels vary among trophoblast cell types, suggesting that imbalances in HERV expression may lead to adverse pregnancy outcomes by affecting the regulation of fusion events in the placenta.
Article Synopsis
- A model using pluripotent stem cells exposed to BMP4 and specific inhibitors generated various types of trophoblasts, including cytotrophoblast and syncytiotrophoblast.
- At day 8, single nuclei RNA sequencing identified two main groups of trophoblast clusters with differing characteristics and gene expressions related to trophoblast identity.
- The findings suggest a complex emergence of trophoblast lineages and emphasize the need for further studies to understand these developmental processes better.
Background: Expression of angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), host molecules required for viral entry, may underlie sex differences in vulnerability to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated whether placental ACE2 and TMPRSS2 expression vary by fetal sex in the presence of maternal SARS-CoV-2 infection.
Methods: Placental ACE2 and TMPRSS2 expression was quantified by quantitative reverse transcription polymerase chain reaction (RT-PCR) and by Western blot in 68 pregnant women (38 SARS-CoV-2 positive, 30 SARS-CoV-2 negative) delivering at Mass General Brigham from April to June 2020.
Background: SARS-CoV-2 infection in term placenta is rare. However, growing evidence suggests that susceptibility of the human placenta to infection may vary by gestational age and pathogen. For several viral infections, susceptibility appears to be greatest during early gestation.
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- Phantom hCG is a condition where nonpregnant patients test positive for hCG, which can mislead clinicians to mistakenly diagnose cancer.
- This situation often leads to unnecessary treatments like chemotherapy or hysterectomy due to the false diagnosis.
- The article discusses various causes for elevated hCG levels in nonpregnant individuals and suggests a structured diagnostic method for clinicians to address this issue effectively.
Article Synopsis
- Gestational diabetes mellitus (GDM) is a common pregnancy complication leading to abnormalities in placental growth and function.
- Research aims to explore how GDM affects placentas and when these changes occur during pregnancy, particularly comparing them to uncomplicated pregnancies.
- The role of maternal obesity in influencing placental development in GDM pregnancies is under-explored, warranting more investigation into early pregnancy disruptions.
There is a persistent male bias in the prevalence and severity of COVID-19 disease. Underlying mechanisms accounting for this sex difference remain incompletely understood. Interferon responses have been implicated as a modulator of disease in adults, and play a key role in the placental anti-viral response.
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