FANCA Promotes DNA Double-Strand Break Repair by Catalyzing Single-Strand Annealing and Strand Exchange.

FANCA is a component of the Fanconi anemia (FA) core complex that activates DNA interstrand crosslink repair by monoubiquitination of FANCD2. Here, we report that purified FANCA protein catalyzes bidirectional single-strand annealing (SA) and strand exchange (SE) at a level comparable to RAD52, while a disease-causing FANCA mutant, F1263Δ, is defective in both activities. FANCG, which directly interacts with FANCA, dramatically stimulates its SA and SE activities. Alternatively, FANCB, which does not directly interact with FANCA, does not stimulate this activity. Importantly, five other patient-derived FANCA mutants also exhibit deficient SA and SE, suggesting that the biochemical activities of FANCA are relevant to the etiology of FA. A cell-based DNA double-strand break (DSB) repair assay demonstrates that FANCA plays a direct role in the single-strand annealing sub-pathway (SSA) of DSB repair by catalyzing SA, and this role is independent of the canonical FA pathway and RAD52.

Functional modulation of lysophosphatidic acid type 2 G-protein coupled receptor facilitates alveolar bone formation.

Lipid biosynthesis is recently studied its functions in a range of cellular physiology including differentiation and regeneration. However, it still remains to be elucidated in its precise function. To reveal this, we evaluated the roles of lysophosphatidic acid (LPA) signaling in alveolar bone formation using the LPA type 2 receptor (LPAR2) antagonist AMG-35 (Amgen Compound 35) using tooth loss without periodontal disease model which would be caused by trauma and usually requires a dental implant to restore masticatory function. In this study, in vitro cell culture experiments in osteoblasts and periodontal ligament fibroblasts revealed cell type-specific responses, with AMG-35 modulating osteogenic differentiation in osteoblasts in vitro. To confirm the in vivo results, we employed a mouse model of tooth loss without periodontal disease. Five to 10 days after tooth extraction, AMG-35 facilitated bone formation in the tooth root socket as measured by immunohistochemistry for differentiation markers KI67, Osteocalcin, Periostin, RUNX2, transforming growth factor beta 1 (TGF-ß1) and SMAD2/3. The increased expression and the localization of these proteins suggest that AMG-35 elicits osteoblast differentiation through TGF-ß1 and SMAD2/3 signaling. These results indicate that LPAR2/TGF-ß1/SMAD2/3 represents a new signaling pathway in alveolar bone formation and that local application of AMG-35 in traumatic tooth loss can be used to facilitate bone regeneration and healing for further clinical treatment.

Independently paced Ca2+ oscillations in progenitor and differentiated cells in an ex vivo epithelial organ.

Cytosolic Ca2+ is a highly dynamic, tightly regulated and broadly conserved cellular signal. Ca2+ dynamics have been studied widely in cellular monocultures, yet organs in vivo comprise heterogeneous populations of stem and differentiated cells. Here, we examine Ca2+ dynamics in the adult Drosophila intestine, a self-renewing epithelial organ in which stem cells continuously produce daughters that differentiate into either enteroendocrine cells or enterocytes. Live imaging of whole organs ex vivo reveals that stem-cell daughters adopt strikingly distinct patterns of Ca2+ oscillations after differentiation: enteroendocrine cells exhibit single-cell Ca2+ oscillations, whereas enterocytes exhibit rhythmic, long-range Ca2+ waves. These multicellular waves do not propagate through immature progenitors (stem cells and enteroblasts), of which the oscillation frequency is approximately half that of enteroendocrine cells. Organ-scale inhibition of gap junctions eliminates Ca2+ oscillations in all cell types - even, intriguingly, in progenitor and enteroendocrine cells that are surrounded only by enterocytes. Our findings establish that cells adopt fate-specific modes of Ca2+ dynamics as they terminally differentiate and reveal that the oscillatory dynamics of different cell types in a single, coherent epithelium are paced independently.

IL-6 Inhibitory Compounds from the Aerial Parts of Piper attenuatum and Their Anticancer Activities on Ovarian Cancer Cell Lines.

Piper attenuatum Buch-Ham, a perennial woody vine belonging to the Piperaceae family, is traditionally used in Southeast Asia for treating various ailments such as malaria, headache, and hepatitis. This study described the isolation and identification of three new compounds, piperamides I-III (1-3), which belong to the maleimide-type alkaloid skeletons, along with fifteen known compounds (4-18) from the methanol extract of the aerial parts of P. attnuatum. Their chemical structures were elucidated using spectroscopic methods (UV, IR, ESI-Q-TOF-MS, and 1D/2D NMR). All the isolates were evaluated for their ability to inhibit IL-6 activity in the human embryonic kidney-Blue™ IL-6 cell line and their cytotoxic activity against ovarian cancer cell lines (SKOV3/SKOV3-TR) and chemotherapy-resistant variants (cisplatin-resistant A2780/paclitaxel-resistant SKOV3). The compounds 3, 4, 11, 12, 17, and 18 exhibited IL-6 inhibition comparable to that of the positive control bazedoxifene. Notably, compound 12 displayed the most potent anticancer effect against all the tested cancer cell lines. These findings highlight the importance of researching the diverse activities of both known and newly discovered natural products to fully unlock their potential therapeutic benefits.

The role of O-GlcNAcylation mediated by OGT during tooth development.

To understand the mechanisms underlying tooth morphogenesis, we examined the developmental roles of important posttranslational modification, O-GlcNAcylation, which regulates protein stability and activity by the addition and removal of a single sugar (O-GlcNAc) to the serine or threonine residue of the intracellular proteins. Tissue and developmental stage-specific immunostaining results against O-GlcNAc and O-GlcNAc transferase (OGT) in developing tooth germs would suggest that O-GlcNAcylation is involved in tooth morphogenesis, particularly in the cap and secretory stage. To evaluate the developmental function of OGT-mediated O-GlcNAcylation, we employed an in vitro tooth germ culture method at E14.5, cap stage before secretory stage, for 1 and 2 days, with or without OSMI-1, a small molecule OGT inhibitor. To examine the mineralization levels and morphological changes, we performed renal capsule transplantation for one and three weeks after 2 days of in vitro culture at E14.5 with OSMI-1 treatment. After OGT inhibition, morphological and molecular alterations were examined using histology, immunohistochemistry, real-time quantitative polymerase chain reaction, in situ hybridization, scanning electron microscopy, and ground sectioning. Overall, inhibition of OGT resulted in altered cellular physiology, including proliferation, apoptosis, and epithelial rearrangements, with significant changes in the expression patterns of ß-catenin, fibroblast growth factor 4 (fgf4), and sonic hedgehog (Shh). Moreover, renal capsule transplantation and immunolocalizations of Amelogenin and Nestin results revealed that OGT-inhibited tooth germs at cap stage exhibited with structural changes in cuspal morphogenesis, amelogenesis, and dentinogenesis of the mineralized tooth. Overall, we suggest that OGT-mediated O-GlcNAcylation regulates cell signaling and physiology in primary enamel knot during tooth development, thus playing an important role in mouse molar morphogenesis.

Developmental function of Piezo1 in mouse submandibular gland morphogenesis.

Mechanically activated factors are important in organogenesis, especially in the formation of secretory organs, such as salivary glands. Piezo-type mechanosensitive ion channel component 1 (Piezo1), although previously studied as a physical modulator of the mechanotransduction, was firstly evaluated on its developmental function in this study. The detailed localization and expression pattern of Piezo1 during mouse submandibular gland (SMG) development were analyzed using immunohistochemistry and RT-qPCR, respectively. The specific expression pattern of Piezo1 was examined in acinar-forming epithelial cells at embryonic day 14 (E14) and E16, which are important developmental stages for acinar cell differentiation. To understand the precise function of Piezo1 in SMG development, siRNA against Piezo1 (siPiezo1) was employed as a loss-of-function approach, during in vitro organ cultivation of SMG at E14 for the designated period. Alterations in the histomorphology and expression patterns of related signaling molecules, including Bmp2, Fgf4, Fgf10, Gli1, Gli3, Ptch1, Shh, and Tgfß-3, were examined in acinar-forming cells after 1 and 2 days of cultivation. Particularly, altered localization patterns of differentiation-related signaling molecules including Aquaporin5, E-cadherin, Vimentin, and cytokeratins would suggest that Piezo1 modulates the early differentiation of acinar cells in SMGs by modulating the Shh signaling pathway.

Exosomal miR-184 in the aqueous humor of patients with central serous chorioretinopathy: a potential diagnostic and prognostic biomarker.

BACKGROUND: Central serous chorioretinopathy (CSC) is the fourth most prevalent retinal disease leading to age-related macular degeneration (AMD) and retinal atrophy. However, CSC's pathogenesis and therapeutic target need to be better understood. RESULTS: We investigated exosomal microRNA in the aqueous humor of CSC patients using next-generation sequencing (NGS) to identify potential biomarkers associated with CSC pathogenesis. Bioinformatic evaluations and NGS were performed on exosomal miRNAs obtained from AH samples of 62 eyes (42 CSC and 20 controls). For subgroup analysis, patients were divided into treatment responders (CSC-R, 17 eyes) and non-responders (CSC-NR, 25 eyes). To validate the functions of miRNA in CECs, primary cultured-human choroidal endothelial cells (hCEC) of the donor eyes were utilized for in vitro assays. NGS detected 376 miRNAs. Our results showed that patients with CSC had 12 significantly upregulated and 17 downregulated miRNAs compared to controls. miR-184 was significantly upregulated in CSC-R and CSC-NR patients compared to controls and higher in CSC-NR than CSC-R. In vitro assays using primary cultured-human choroidal endothelial cells (hCEC) demonstrated that miR-184 suppressed the proliferation and migration of hCECs. STC2 was identified as a strong candidate for the posttranscriptional down-regulated target gene of miR-184. CONCLUSION: Our findings suggest that exosomal miR-184 may serve as a biomarker reflecting the angiostatic capacity of CEC in patients with CSC.

Ultrasonographic analysis of facial skin thickness in relation to age, site, sex, and body mass index.

BACKGROUND: Numerous nonsurgical but invasive cosmetic procedures are performed blindly in the dermis or subcutaneous fat layer of the facial skin. OBJECTIVES: To measure the numerical skin thickness of the facial areas where dermatological procedures are performed by applying ultrasound techniques, and to make it possible to estimate the skin thickness by investigating the influence of several individual constitutional factors such as age, sex, and body mass index (BMI), so that these variables can be applied to estimate skin thickness. MATERIALS AND METHODS: Skin thickness was measured at eight different facial points using an ultrasound machine (Affiniti 50; Philips Inc.). Demographic data were gathered using questionnaires. Manual BMI was calculated from the weight and height of each participant, and individual BMI measurements were performed using a body composition analyzer. RESULTS: In terms of whole skin thickness, the thickest point was the mouth corner, and the thinnest point was the lateral forehead. The thickest point in the epidermis was the chin, and the thinnest point was the nasolabial fold. The thickest point in the dermis was the corner of the mouth, and the thinnest was the lateral forehead. Full skin thickness and dermal thickness were mostly lower in females. Skin thickness was not significantly correlated with BMI. CONCLUSION: The skin thickness at different points on the face was variable, and realistic data about skin thickness can be obtained by in vivo ultrasonographic analysis of the skin.

The effects of xeno-free cryopreservation on the contractile properties of human iPSC derived cardiomyocytes.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have advanced our ability to study the basic function of the heart and model cardiac diseases. Due to the complexities in stem cell culture and differentiation protocols, many researchers source their hiPSC-CMs from collaborators or commercial biobanks. Generally, the field has assumed the health of frozen cardiomyocytes is unchanged if the cells adhere to the substrate and commence beating. However, very few have investigated the effects of cryopreservation on hiPSC-CM's functional and transcriptional health at the cellular and molecular level. Here we review methods and challenges associated with cryopreservation, and examine the effects of cryopreservation on the functionality (contractility and calcium handling) and transcriptome of hiPSC-CMs from six healthy stem cell lines. Utilizing protein patterning methods to template physiological cell aspect ratios (7:1, length:width) in conjunction with polyacrylamide (PA) hydrogels, we measured changes in force generation and calcium handling of single hiPSC-CMs. We observed that cryopreservation altered the functionality and transcriptome of hiPSC-CMs towards larger sizes and contractile force as assessed by increased spread area and volume, single cell traction force microscopy and delayed calcium dynamics. hiPSC-CMs are broadly used for basic science research, regenerative medicine, and testing biological therapeutics. This study informs the design of experiments utilizing hiPSC-CMs to avoid confounding functional changes due to cryopreservation with other treatments.

Cardiovascular Autonomic Regulation, ETCO2 and the Heart Rate Response to the Tilt Table Test in Patients with Orthostatic Intolerance.

Chronic orthostatic intolerance (COI) is defined by changes in heart rate (HR), blood pressure (BP), respiration, symptoms of cerebral hypoperfusion and sympathetic overactivation. Postural tachycardia syndrome (POTS) is the most common form of COI in young adults and is defined by an orthostatic increase in heart rate (HR) of ≥ 30 bpm in the absence of orthostatic hypotension. However, some patients referred for evaluation of COI symptoms do not meet the orthostatic HR response criterion of POTS despite debilitating symptoms. Such patients are ill defined, posing diagnostic and therapeutic challenges. This study explored the relationship among cardiovascular autonomic control, the orthostatic HR response, EtCO2 and the severity of orthostatic symptoms and fatigue in patients referred for evaluation of COI. Patients (N = 108) performed standardized testing protocol of the Autonomic Reflex Screen and completed the Composite Autonomic Symptom Score (COMPASS-31) and the Fatigue Severity Scale (FSS). Greater severity of COI was associated with younger age, larger phase IV amplitude in the Valsalva maneuver and lower adrenal baroreflex sensitivity. Greater fatigue severity was associated with a larger reduction in ETCO2 during 10 min of head-up tilt (HUT) and reduced low-frequency (LF) power of heart rate variability. This study suggests that hemodynamic changes associated with the baroreflex response and changes in EtCO2 show a stronger association with the severity of orthostatic symptoms and fatigue than the overall orthostatic HR response in patients with COI.

Chronic Alcohol Exposure Promotes Cancer Stemness and Glycolysis in Oral/Oropharyngeal Squamous Cell Carcinoma Cell Lines by Activating NFAT Signaling.

Alcohol consumption is associated with an increased risk of several cancers, including oral/oropharyngeal squamous cell carcinoma (OSCC). Alcohol also enhances the progression and aggressiveness of existing cancers; however, its underlying molecular mechanism remains elusive. Especially, the local carcinogenic effects of alcohol on OSCC in closest contact with ingestion of alcohol are poorly understood. We demonstrated that chronic ethanol exposure to OSCC increased cancer stem cell (CSC) populations and their stemness features, including self-renewal capacity, expression of stem cell markers, ALDH activity, and migration ability. The ethanol exposure also led to a significant increase in aerobic glycolysis. Moreover, increased aerobic glycolytic activity was required to support the stemness phenotype of ethanol-exposed OSCC, suggesting a molecular coupling between cancer stemness and metabolic reprogramming. We further demonstrated that chronic ethanol exposure activated NFAT (nuclear factor of activated T cells) signaling in OSCC. Functional studies revealed that pharmacological and genetic inhibition of NFAT suppressed CSC phenotype and aerobic glycolysis in ethanol-exposed OSCC. Collectively, chronic ethanol exposure promotes cancer stemness and aerobic glycolysis via activation of NFAT signaling. Our study provides a novel insight into the roles of cancer stemness and metabolic reprogramming in the molecular mechanism of alcohol-mediated carcinogenesis.

Dynamic thermal imaging for pigmented basal cell carcinoma and seborrheic keratosis.

BACKGROUND: Clinical differentiation between pigmented basal cell carcinoma (BCC) and seborrheic keratosis (SK) can sometimes be difficult. Noninvasive diagnostic technologies, such as thermal imaging, can be helpful in these situations. This study explored the use of dynamic thermal imaging (DTI), which records thermal images after the application of external thermal stimuli (heat or cold) for the differential diagnosis of pigmented BCC and SK. MATERIALS AND METHODS: Twenty-two patients with pigmented BCC and 15 patients with SK participated in this study. Dynamic thermal images of lesions (pigmented BCC or SK) and control sites (contralateral normal skin) were recorded after the heat and cold stimuli. Temperature changes in the region of interest (ROI) are plotted as a thermal response graph. After fitting an exponential equation to each thermal response graph, the rate constants were compared between groups (pigmented BCC versus control, SK versus control). RESULTS: The thermal response graphs revealed that the average temperature of pigmented BCC showed faster thermal recovery to baseline than the control site. There was a significant difference in the rate constants of the fitted exponential equations between the pigmented BCCs and the control sites (p<.001). However, we did not find a significantly different thermal recovery pattern between SK lesions and control sites. CONCLUSIONS: DTI can be used as a diagnostic tool for distinguishing pigmented BCC from SK by comparing thermal recovery patterns between target lesions (pigmented BCC or SK) and the control site.

Retinal VEGFA maintains the ultrastructure and function of choriocapillaris by preserving the endothelial PLVAP.

Fenestrations in choriocapillaris act as a window for molecular transports between the retina and choroid, and is crucial for maintaining visual function. Plasmalemma vesicle-associated protein (PLVAP) is essential for the development of endothelial fenestrations. There is little knowledge about how the choriocapillaris maintains the fenestrated endothelium. This study aimed to evaluate the role of vascular endothelial growth factor-A (VEGFA)-PLVAP axis in the maintenance of choroidal fenestrations using oxygen-induced retinopathy (OIR) model. In C57BL/6 J mice, the mice with OIR on postnatal day 12 (P12) presented thicker endothelium and less fenestration compared to the non-OIR mice. However, the OIR on 17 mice showed thinner endothelium with more fenestration compared to OIR on P12. In vivo angiography demonstrated the presence of hyperpermeable choroidal vessels on P17 in OIR mice. These dramatic changes in choriocapillaris were not observed in the BALB/cJ OIR model. The ultrastructural changes in the choriocapillaris were correlated with temporal variations in the expression of VEGFA and PLVAP. VEGFA stimulated expression of PLVAP in the choroidal endothelial cells. Loss of PLVAP disrupts the polarized structure of the choriocapillaris leading to retinal degeneration. These results indicate that the expression of retinal VEGFA is essential for maintaining the structure and function of choriocapillaris by preserving the endothelial PLVAP.

Psychopharmacology of COVID-19.

Background: With the rapid, global spread of severe acute respiratory syndrome coronavirus 2, hospitals have become inundated with patients suffering from coronavirus disease 2019. Consultation-liaison psychiatrists are actively involved in managing these patients and should familiarize themselves with how the virus and its proposed treatments can affect psychotropic management. The only Food and Drug Administration-approved drug to treat COVID-19 is remdesivir, and other off-label medications used include chloroquine and hydroxychloroquine, tocilizumab, lopinavir/ritonavir, favipiravir, convalescent plasma therapy, azithromycin, vitamin C, corticosteroids, interferon, and colchicine. Objective: To provide an overview of the major safety considerations relevant to clinicians who prescribe psychotropics to patients with COVID-19, both related to the illness and its proposed treatments. Methods: In this targeted review, we performed structured literature searches in PubMed to identify articles describing the impacts of COVID-19 on different organ systems, the neuropsychiatric adverse effects of treatments, and any potential drug interactions with psychotropics. The articles most relevant to this one were included. Results: COVID-19 impacts multiple organ systems, including gastrointestinal, renal, cardiovascular, pulmonary, immunological, and hematological systems. This may lead to pharmacokinetic changes that impact psychotropic medications and increase sensitivity to psychotropic-related adverse effects. In addition, several proposed treatments for COVID-19 have neuropsychiatric effects and potential interactions with commonly used psychotropics. Conclusions: Clinicians should be aware of the need to adjust existing psychotropics or avoid using certain medications in some patients with COVID-19. They should also be familiar with neuropsychiatric effects of medications being used to treat this disease. Further research is needed to identify strategies to manage psychiatric issues in this population.

The Role of Amino Acids in Neurotransmission and Fluorescent Tools for Their Detection.

Neurotransmission between neurons, which can occur over the span of a few milliseconds, relies on the controlled release of small molecule neurotransmitters, many of which are amino acids. Fluorescence imaging provides the necessary speed to follow these events and has emerged as a powerful technique for investigating neurotransmission. In this review, we highlight some of the roles of the 20 canonical amino acids, GABA and ß-alanine in neurotransmission. We also discuss available fluorescence-based probes for amino acids that have been shown to be compatible for live cell imaging, namely those based on synthetic dyes, nanostructures (quantum dots and nanotubes), and genetically encoded components. We aim to provide tool developers with information that may guide future engineering efforts and tool users with information regarding existing indicators to facilitate studies of amino acid dynamics.

Building evidence to reduce inequities in youth physical activity and obesity: Introduction to the Physical Activity Research Center (PARC) Special Section.

This guest editorial introduces the rationale and goals of the Physical Activity Research Center. It provides an overview of the five papers in this Special Section plus six commissioned studies intended to inform advocacy efforts.

Increased risk of hospital admission for ICD-9-CM psychotic episodes following admission for epilepsy.

OBJECTIVE: To determine whether epilepsy admissions are associated with a higher readmission risk for psychotic episodes compared to admissions for other medical causes. METHODS: The Nationwide Readmissions Database is a nationally representative dataset from 2013. We used International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes to identify medical conditions. There were 58 278 index admissions for epilepsy, and this group was compared against admissions for stroke (n = 215 821) and common medical causes (pneumonia, urinary tract infection [UTI], congestive heart failure [CHF], and chronic obstructive pulmonary disease [COPD], n = 973 078). Readmission rates for psychotic episodes within 90 days from discharge for index hospitalizations were calculated. Cox regression was used to test for associations between admission type and readmission for psychotic episodes up to 1 year after index admission, in univariate models and adjusted for multiple medical, social, and psychiatric variables. RESULTS: Up to 90 days from index admission, there were 683/100 000 readmissions for psychotic episodes in the epilepsy group, 92/100 000 in the stroke group, and 58-206/100 000 in the medical group. The relative rate of readmission in the epilepsy group was highest in the first 30 days following index admission (311/100 000). Unadjusted hazard ratio (HR) for readmission for psychotic episodes within 1 year in the epilepsy group compared to the stroke group was 6.58 (95% confidence interval [CI] 5.69-7.61, P < 2 × 10-16 ), and 4.41 compared to the medical group (95% CI 4.00-4.85, P < 2 × 10-16 ). The fully adjusted HR for readmission in the epilepsy group remained elevated at 3.63 compared to the stroke group (95% CI 3.08-4.28, P < 2 × 10-16 ), and 1.95 compared to the medical group (95% CI 1.76-2.15, P < 2 × 10-16 ). Confounding factors most strongly associated with psychosis readmission were documented psychosis history at the time of index admission, younger age, and lower income quartile. SIGNIFICANCE: An epilepsy admission was independently associated with subsequent hospital readmission for psychotic episodes, even after adjustment for confounding variables.

Risk of readmission for suicide attempt after epilepsy hospitalization.

OBJECTIVE: The objective of this study was to examine if epilepsy admissions are associated with a higher readmission risk for suicide attempt, independent of psychiatric comorbidity, compared with index admissions for other medical causes. METHODS: The Nationwide Readmissions Database is a nationally representative dataset containing data from roughly 15 million hospital discharges. Analysis of International Classification of Disease Clinical Modification 9 (ICD-9-CM) codes in the year 2013 revealed 58,278 index admissions for epilepsy; this group was compared with admissions for stroke (N=215,821) and common medical causes (N=973,078). Ninety-day readmission rates for suicide attempts were calculated. Cox regression tested for associations between admission type and suicide attempt readmissions up to 1year following index admission. RESULTS: There were 402/100,000 readmissions for suicide attempt within 90days from index admission in the group with epilepsy; 43/100,000 in the stroke group; and between 37 and 89/100,000 in the medical group. Unadjusted hazard ratios (HR) for suicide readmissions within 1year in the group with epilepsy compared with the stroke group were 9.61 (95% confidence interval (CI): 7.69-11.90, p<2.0×10-16) and 5.02 compared with the medical group (95% CI: 4.40-5.73, p<2.0×10-16). The HR for readmission in the group with epilepsy, after adjustment for sociodemographic and psychiatric variables, were elevated at 4.91 compared with the stroke group (95% CI: 3.83-6.27, p<2.0×10-16), and 2.66 compared with the medical group (95% CI: 2.32-3.05, p<2.0×10-16). CONCLUSION: Independent of psychiatric comorbidities, epilepsy admissions may be independently associated with more than a threefold increased risk of hospital readmission for suicide in the year following index admission in comparison with patients recently hospitalized because of stroke or other common medical disorders.

Vulvar Varicosities: A Review.

BACKGROUND: Vulvar varicosities (VV) are dilated and tortuous veins occurring within the external female genitalia. Patients may seek treatment of these varices for both medical and cosmetic purposes. In some patients, VV may be associated with a chronic pelvic pain syndrome called pelvic congestion syndrome (PCS). OBJECTIVE: To review the English language literature on VV in both pregnant and nonpregnant women. MATERIALS AND METHODS: A literature search pertaining to vulvar varicosities and PCS was performed using PubMed and Google Scholar databases. RESULTS: There is an overall paucity of literature discussing VV, particularly in nonpregnant women without PCS. Management options for VV include compression, sclerotherapy, embolization, and surgical ligation. Treatment can be dependent on the coexistence of pelvic or leg varicosities and may require referral to a vein specialist for advanced imaging techniques and procedures. Direct sclerotherapy to VV may not provide adequate treatment if pelvic or leg varices are also present. CONCLUSION: In women with persistent VV, imaging studies should be obtained before treatment to evaluate the surrounding venous anatomy of the pelvis and leg, as the results often affect the treatment approach. Patients presenting with VV and chronic pelvic pain should be evaluated for PCS.