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1.
Semin Perinatol ; 48(4): 151923, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38960750

ABSTRACT

The COVID-19 pandemic exposed and exacerbated persistent health inequities in perinatal populations, resulting in disparities of maternal and fetal complications. In this narrative review, we present an adapted conceptual framework of perinatal social determinants of health in the setting of the COVID-19 pandemic and use this framework to contextualize the literature regarding disparities in COVID-19 vaccination and infection. We synthesize how elements of the structural context, individual socioeconomic position, and concrete intermediary determinants influence each other and perinatal COVID-19 vaccination and infection, arguing that systemic inequities at each level contribute to observed disparities in perinatal health outcomes. From there, we identify gaps in the literature, propose mechanisms for observed disparities, and conclude with a discussion of strategies to mitigate them.


Subject(s)
COVID-19 Vaccines , COVID-19 , Healthcare Disparities , Pregnancy Complications, Infectious , SARS-CoV-2 , Vaccination , Humans , COVID-19/prevention & control , Pregnancy , Female , Pregnancy Complications, Infectious/prevention & control , Social Determinants of Health , Infant, Newborn , Socioeconomic Factors , Perinatal Care/methods , Health Status Disparities
2.
Urogynecology (Phila) ; 29(2): 175-182, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36735431

ABSTRACT

IMPORTANCE: Constipation is common after pelvic surgery, and studies suggest that surgeons underestimate the negative impact of constipation on patients. Patients undergoing pelvic reconstructive surgery are a unique population requiring special consideration in the prevention and management of constipation. OBJECTIVE: This study aimed to systematically review the literature to identify evidence for prevention of postoperative constipation with medications or fiber in patients undergoing reconstructive pelvic surgery. STUDY DESIGN: A structured literature search was performed of five databases (MEDLINE, Embase, Scopus, Web of Science, the Cochrane Library) from inception to June 2022 for studies of postoperative laxative or fiber use in adult patients undergoing benign pelvic reconstructive surgery. Studies of preoperative bowel preparation and nonsurgical patients were excluded. Data on postoperative constipation were extracted for a qualitative analysis of the literature. Grading of Recommendations Assessment, Development, and Evaluation methodology was applied to assess the quality of evidence. RESULTS: We identified 86 references after deduplication. Only 4 studies with a total of 344 patients were eligible for inclusion in the review. The included studies were all randomized controlled trials assessing time to first bowel movement with the earliest published in 2010. Laxative use decreased constipation more than placebo. Multiple-agent laxative use appeared to decrease bothersome constipation more than single-agent docusate. Preoperative fiber did not decrease constipation. By Grading of Recommendations Assessment, Development, and Evaluation criteria, all four studies provide moderate-quality evidence. CONCLUSIONS: Few studies have investigated laxative regimens in patients after urogynecologic surgery. The available literature is moderate quality and suggests benefit of multiple-agent treatment over docusate only or no treatment.


Subject(s)
Dioctyl Sulfosuccinic Acid , Laxatives , Adult , Humans , Laxatives/therapeutic use , Dioctyl Sulfosuccinic Acid/pharmacology , Constipation/etiology , Defecation
3.
AACE Clin Case Rep ; 8(1): 19-21, 2022.
Article in English | MEDLINE | ID: mdl-35097196

ABSTRACT

BACKGROUND: Health care providers routinely discontinue testosterone in transgender men undergoing oocyte retrieval. To date, there is little literature to support such discontinuation. The sudden drop in testosterone levels can be distressing for transgender men. The objective of this report was to describe a case study of successful reciprocal in vitro fertilization (IVF) using oocytes retrieved from a transgender man who remained on testosterone during the entire course of gonadotropin controlled ovarian stimulation and retrieval. CASE REPORT: A 33-year-old gravida 0 transgender man and his partner, a 42-year-old gravida 0 cisgender woman, presented to an outpatient clinic in 2017 seeking reciprocal IVF. Both patients were healthy with no significant past medical history. The transgender patient reported a 10-year history of testosterone hormone therapy. Both patients reported no other medication use. The transgender man underwent a 14-day course of ovarian stimulation before oocytes were retrieved. An oocyte was then fertilized and implanted into the uterus of the patient's cisgender female partner. The reciprocal IVF resulted in an uncomplicated, full-term pregnancy with vaginal delivery. The child is now 2 years old and developmentally normal. DISCUSSION: To our knowledge, this is the first report of a live birth from an oocyte retrieved from a transgender man who continued to use testosterone throughout assisted reproduction. CONCLUSION: Fertility preservation options for transmasculine people may include stimulated egg retrieval if the ovaries are left in place even when the patients remain on testosterone therapy.

4.
Hum Genet ; 138(10): 1183-1200, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31471722

ABSTRACT

The glutamate pyruvate transaminase 2 (GPT2) gene produces a nuclear-encoded mitochondrial enzyme that catalyzes the reversible transfer of an amino group from glutamate to pyruvate, generating alanine and alpha-ketoglutarate. Recessive mutations in GPT2 have been recently identified in a new syndrome involving intellectual and developmental disability (IDD), postnatal microcephaly, and spastic paraplegia. We have identified additional families with recessive GPT2 mutations and expanded the phenotype to include small stature. GPT2 loss-of-function mutations were identified in four families, nine patients total, including: a homozygous mutation in one child [c.775T>C (p.C259R)]; compound heterozygous mutations in two siblings [c.812A>C (p.N271T)/c.1432_1433delGT (p.V478Rfs*73)]; a novel homozygous, putative splicing mutation [c.1035C>T (p.G345=)]; and finally, a recurrent mutation, previously identified in a distinct family [c.1210C>T (p.R404*)]. All patients were diagnosed with IDD. A majority of patients had remarkably small stature throughout development, many < 1st percentile for height and weight. Given the potential biological function of GPT2 in cellular growth, this phenotype is strongly suggestive of a newly identified clinical susceptibility. Further, homozygous GPT2 mutations manifested in at least 2 of 176 families with IDD (approximately 1.1%) in a Pakistani cohort, thereby representing a relatively common cause of recessive IDD in this population, with recurrence of the p.R404* mutation in this population. Based on variants in the ExAC database, we estimated that approximately 1 in 248 individuals are carriers of moderately or severely deleterious variants in GPT2.


Subject(s)
Developmental Disabilities/diagnosis , Developmental Disabilities/genetics , Genes, Recessive , Genetic Predisposition to Disease , Mutation , Phenotype , Transaminases/genetics , Adolescent , Alleles , Amino Acid Substitution , Developmental Disabilities/metabolism , Enzyme Activation , Exons , Female , Gene Frequency , Genetic Association Studies , Genetics, Population , Genotype , Humans , Intellectual Disability/diagnosis , Intellectual Disability/genetics , Magnetic Resonance Imaging , Male , Mitochondria/genetics , Mitochondria/metabolism , Models, Molecular , Pedigree , Protein Conformation , RNA Splice Sites , Sequence Analysis, DNA , Structure-Activity Relationship , Transaminases/chemistry , Transaminases/metabolism
5.
Nat Chem ; 10(12): 1267, 2018 12.
Article in English | MEDLINE | ID: mdl-30420778

ABSTRACT

In the version of this Article originally published online, the upper right panel of Fig. 5a was mistakenly a repeat of the lower right panel. This has now been corrected in all versions of the Article.

6.
Nat Chem ; 10(12): 1213-1221, 2018 12.
Article in English | MEDLINE | ID: mdl-30297750

ABSTRACT

Inhibiting the interaction between amyloid-ß (Aß) and a neuronal cell surface receptor, LilrB2, has been suggested as a potential route for treating Alzheimer's disease. Supporting this approach, Alzheimer's-like symptoms are reduced in mouse models following genetic depletion of the LilrB2 homologue. In its pathogenic, oligomeric state, Aß binds to LilrB2, triggering a pathway to synaptic loss. Here we identify the LilrB2 binding moieties of Aß (16KLVFFA21) and identify its binding site on LilrB2 from a crystal structure of LilrB2 immunoglobulin domains D1D2 complexed to small molecules that mimic phenylalanine residues. In this structure, we observed two pockets that can accommodate the phenylalanine side chains of KLVFFA. These pockets were confirmed to be 16KLVFFA21 binding sites by mutagenesis. Rosetta docking revealed a plausible geometry for the Aß-LilrB2 complex and assisted with the structure-guided selection of small molecule inhibitors. These molecules inhibit Aß-LilrB2 interactions in vitro and on the cell surface and reduce Aß cytotoxicity, which suggests these inhibitors are potential therapeutic leads against Alzheimer's disease.


Subject(s)
Alzheimer Disease/drug therapy , Amyloid beta-Peptides/antagonists & inhibitors , Amyloid beta-Peptides/toxicity , Drug Design , Membrane Glycoproteins/metabolism , Receptors, Immunologic/metabolism , Small Molecule Libraries/pharmacology , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Amyloid beta-Peptides/chemistry , Amyloid beta-Peptides/metabolism , Animals , Cell Survival/drug effects , Dose-Response Relationship, Drug , Humans , Membrane Glycoproteins/chemistry , Mice , Molecular Structure , Neurons/drug effects , Receptors, Immunologic/chemistry , Small Molecule Libraries/chemical synthesis , Small Molecule Libraries/chemistry , Structure-Activity Relationship
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