Impact of Annexin A2 on virus life cycles.

Due to the limited size of viral genomes, hijacking host machinery by the viruses taking place throughout the virus life cycle is inevitable for the survival and proliferation of the virus in the infected hosts. Recent reports indicated that Annexin A2 (AnxA2), a calcium- and lipid-binding cellular protein, plays an important role as a critical regulator in various steps of the virus life cycle. The multifarious AnxA2 functions in cells, such as adhesion, adsorption, endocytosis, exocytosis, cell proliferation and division, inflammation, cancer metastasis, angiogenesis, etc., are intimately related to the various clinical courses of viral infection. Ubiquitous expression of AnxA2 across multiple cell types indicates the broad range of susceptibility of diverse species of the virus to induce disparate viral disease in various tissues, and intracellular expression of AnxA2 in the cytoplasmic membrane, cytosol, and nucleus suggests the involvement of AnxA2 in the regulation of the different stages of various virus life cycles within host cells. However, it is yet unclear as to the molecular processes on how AnxA2 and the infected virus interplay to regulate virus life cycles and thereby the virus-associated disease courses, and hence elucidation of the molecular mechanisms on AnxA2-mediated virus life cycle will provide essential clues to develop therapeutics deterring viral disease.

Relationship Between Childhood Sexual Abuse, Obesity, and Vulvodynia in Adulthood.

OBJECTIVE: The aim of the study is to assess the relationship between childhood sexual abuse, obesity, and vulvodynia among adult women participating in a population-based longitudinal vulvodynia study. MATERIALS AND METHODS: Surveys assessed health status, diagnoses, risk factors, and screening test outcomes for women with vulvodynia. Associations between childhood sexual abuse (CSA) and obesity, CSA and vulvodynia, and obesity and vulvodynia were investigated. A multivariate model was used to determine if obesity mediates and/or modifies the relationship between CSA and vulvodynia. RESULTS: Of 2,277 women participating in the study, 1,647 completed survey data on CSA at 18 months, body mass index at 24 months, and vulvodynia over the first 54 months of the survey. Mean age was 50.9 ± 15.8 years. Overall, race and ethnicity were 77.4% White, 15.7% Black, 2.4% Hispanic, and 4.5% other. Five hundred thirty-nine participants (32.7%) were obese (body mass index >30) and 468 (28.4%) were overweight. Physical CSA before age of 18 years was reported by 20.0% ( n = 329). During the study, 22.0% ( n = 362) screened positive for vulvodynia on one or more surveys. After controlling for demographic variables, both obesity and screening positive for vulvodynia were associated with a history of CSA before age of 18 years ( p = .013 and p < .001, respectively), but obesity was not associated with screening positive for vulvodynia ( p = .865). In addition, multivariate analysis indicated no mediation of the CSA/vulvodynia relationship by obesity. CONCLUSIONS: Although obesity and vulvodynia were independently associated with a history of CSA, obesity did not mediate or modify the relationship between CSA and vulvodynia in adulthood.

Factors Associated with Provider Practices Related to Infant Feeding in Primary Care Settings: Results from a Pilot Survey.

In 2020, only 25.6% of dyads in the US were exclusively breastfeeding at six months. Previous research has shown that breastfeeding continuation improves when patients receive both prenatal and postpartum support. Additionally, breastfeeding self-efficacy can be directly impacted by interactions with primary healthcare providers. To facilitate improved lactation support and positive interactions with providers related to infant feeding in the primary care setting, a 49-question survey was utilized to conduct a retrospective, cross-sectional study. Using multiple regression analysis, the researchers tested a model to determine if certain factors could predict patients receiving lactation education in the primary care setting. The full model was statistically significant and accounts for 81.8% of the variance (R2 = 0.818, F (7, 21) = 9.015, p < 0.001, CI = 0.728 to 0.910). Variables that contributed significantly to the model included provider age, provider years of experience in maternal-child health, population density of the practice, and average provider preparedness and comfort with lactation support and medical management. As the only modifiable predictor significantly contributing to the model, future research is necessary to develop educational interventions to improve provider preparedness and comfort with lactation support and medical management. Such interventions may significantly improve the frequency of lactation education in primary care settings.

Vulvar Ulcers: An Algorithm to Assist With Diagnosis and Treatment.

OBJECTIVES: Vulvar ulcers can be challenging to diagnose, manage, and treat. Ulcers can be nonspecific in appearance and have many etiologies. Description of the lesion is very important. METHODS: An interactive vulvar ulcer algorithm was created to aid in the evaluation, diagnosis, and treatment of vulvar ulcers. RESULTS: The algorithm flowchart begins with careful history and physical examination. Pending these, specific tests can be obtained to aid in diagnosis. The algorithm also links to appropriate treatments. The algorithm can be accessed on the International Society for the Study of Vulvovaginal Disease Web site ( issvd.org ). Each underlined word in the algorithm is a hyperlink that leads to a wealth of information on the topic that providers can use to direct testing and aid in diagnosis and treatment. CONCLUSIONS: The vulvar ulcer algorithm can help clinicians with diagnosis and treatment plans.

Early childhood teachers' writing beliefs and practices.

This study examined the early writing beliefs, ideas, and practices of 54 early childhood teachers. Teachers completed a survey designed to examine their early writing beliefs and provided definitions about early writing development through a written response. Teachers were also observed in their classrooms and writing practices were coded for instructional strategy employed by the teacher (i.e., modeling and scaffolding approaches) and the instructional focus of these interactions with attention to early writing skill. Teachers' definitions of writing often emphasized specific writing skills, with most teachers emphasizing handwriting. Teachers were observed enacting a range of modeling and scaffolding practices to support early writing, but the majority of interactions focused on handwriting supports. Teachers' definitions of writing and their responses to the teacher belief survey were unrelated to each other, but differentially related to writing skills emphasized in interactions with children. Teachers who identified more than one writing component in their definition were more likely to enact practices to support children's writing concept knowledge, while teachers who espoused more developmentally appropriate early writing beliefs on the survey were more likely to engage children in spelling focused interactions. Findings have implications for the study of teachers' beliefs about writing as well as the need for professional learning supports for preschool teachers.

Resiliency and vulnerability in early grades writing performance during the COVID-19 pandemic.

To explore potential pandemic-related learning gaps on expressive writing skills, predominantly Hispanic (≈50%) and White (≈30%) primary-grade students responded to grade-specific writing prompts in the fall semesters before and after school closures. Responses were evaluated with an analytic rubric consisting of five traits (focus, organization, development, grammar, mechanics), each scored on a 1-4 scale. Data first were analyzed descriptively and, after propensity score weighting, with ordinal response models (for analytic scores) and generalized linear mixed effects models (for composite scores). Compared to first graders in 2019 (n = 310), those in 2020 (n = 203) scored significantly lower overall as well as on all rubric criteria and were more likely to write unintelligible responses. Second graders in 2020 (n = 194) performed significantly lower than those in 2019 (n = 328) in some traits but not all, and there was a widening gap between students who did/not score proficiently. A three-level longitudinal model analyzing the sample of students moving from first to second grade in fall 2020 (n = 90) revealed significant improvements, but students still performed significantly lower than second graders in the previous year. Implications for student resiliency and instructional planning are discussed.

Outcomes After Lysis of Adhesions and Dilator Placement for Treatment of Vulvovaginal Agglutination Due to Lichen Planus.

OBJECTIVE: The aim of the study is to determine intraoperative and postoperative surgical outcomes for the treatment of vulvovaginal agglutination secondary to lichen planus (LP) following a standard protocol using intraoperative dilator placement and postoperative intravaginal steroid use. MATERIALS AND METHODS: This was a retrospective chart review of patients who underwent surgical management of vulvovaginal agglutination due to LP following a protocol that included surgical lysis of vulvovaginal adhesions, intraoperative dilator placement and removal 48 hours later, and high-potency intravaginal corticosteroid and regular dilator use thereafter. Demographic and clinical data were abstracted from the medical record and analyzed using descriptive statistics. RESULTS: Thirty-four patients, with mean age 51.2 ± 11 years and body mass index 32.8 ± 8.5 kg/m 2 , underwent lysis of vulvovaginal adhesions between 1999 and 2021 with 8 different surgeons at a single institution. The mean preoperative, immediate postoperative, and 6-week postoperative vaginal lengths were 2.8 ± 1.8 cm ( n = 18), 8.0 ± 1.9 cm ( n = 21), and 7.9 ± 2.2 cm ( n = 16), respectively. The mean estimated blood loss intraoperatively was 16 ± 15 mL. No patients had a documented surgical site infection or reoperation within 30 days after surgery. Of patients who had it documented ( n = 26), 70% (18/26) reported postoperative sexual activity. Where documented, 100% (18/18) reported preoperative dyspareunia, while 17% (3/18) did postoperatively. Six percent (2/34) had recurrent severe agglutination and 3% (1/34) underwent reoperation. CONCLUSIONS: Lysis of vulvovaginal adhesions, intraoperative dilator placement, and postoperative intravaginal corticosteroids with dilator use is a safe and effective treatment option to restore vaginal length for those with vulvovaginal LP.

Impact of a single-session psychosocial counseling intervention for women with vulvodynia.

OBJECTIVE: To evaluate the impact of a single session of psychosocial counseling on patients with vulvodynia. METHODS: Patients diagnosed with vulvodynia at a vulvovaginal specialty clinic were randomly assigned to receive either a one-on-one 30- to 45-min psychosocial counseling session with a psychosexual counselor plus written educational materials (intervention group) or written materials alone (control group). They completed a survey before and 6 weeks after randomization that included demographic information and validated measures of sexual function and illness perception. RESULTS: Thirty-one of 38 (81.6%) women approached chose to participate; 26 of the 31 (83.9%) completed the 6-week follow-up survey. Only the intervention group showed improvement in knowledge about vulvovaginal and sexual health, as well as in most measures of improvement in illness perception, as measured by the Brief Illness Perception Questionnaire (P < 0.05). When compared directly with those in the control group, patients in the intervention group reported increased understanding of their vulvar symptoms (P < 0.005) and lessened emotional impact of these symptoms (P = 0.035). CONCLUSION: Patients receiving one session of the one-on-one psychosocial counseling intervention reported improved understanding and lessened emotional impact of their vulvar symptoms, compared with the control group. This study suggests that improvement may occur following minimal intervention and supports the need for further study.

Surgical Performance of En Bloc Total Capsulectomy Breast Implant Removal With Uninterrupted Breastfeeding.

INTRODUCTION: A 28-year-old woman was able to maintain lactation for her 21-month-old child through the process of an En Bloc Total Capsulectomy Breast Implant Removal. This case study is important as it exemplifies collaborative care to achieve maintenance of lactation through a surgical procedure. MAIN ISSUE: The participant was providing human milk to her 21-month-old child 4 times per day through breastfeeding and pumping and bottle feeding, and desired to continue lactation through explant surgery. The participant was experiencing Breast Implant Illness, yellowing of the skin and whites of the eyes, bottoming out of the right implant, severe capsular contracture of the right implant causing constant pain, limited mobility of the right arm and shoulder, and concern about an active recall on the brand implant she received. MANAGEMENT: The lactation management began 3 weeks prior to the procedure with the participant expressing enough milk prior to the surgery to allow for human milk feeding from a bottle during the 7-day recovery period as desired. The surgical team and IBCLC selected an appropriate bra for recovery to allow for both appropriate surgical site healing and ease of access for pumping. Exclusive pumping was utilized until surgical drains were removed, after which the participant was able to reintroduce breastfeeding. CONCLUSION: En Bloc Total Capsulectomy Breast Implant Removal can be performed while an individual is lactating without complication, given the appropriate multidisciplinary support. A temporary reduction of ease and efficiency of milk removal is possible post-operatively, in this case resolving within 24 hr.

Surgical Primary Tumor Resection Reduces Accumulation of CD11b+ Myeloid Cells in the Lungs Augmenting the Efficacy of an Intranasal Cancer Vaccination against Secondary Lung Metastasis.

A hallmark of effective cancer treatment is the prevention of tumor reoccurrence and metastasis to distal organs, which are responsible for most cancer deaths. However, primary tumor resection is expected to be curative as most solid tumors have been shown both experimentally and clinically to accelerate metastasis to distal organs including the lungs. In this study, we evaluated the efficacy of our engineered nasal nano-vaccine (CpG-NP-Tag) in reducing accelerated lung metastasis resulting from primary tumor resection. Cytosine-phosphate-guanine oligonucleotide [CpG ODN]-conjugated nanoparticle [NP] encapsulating tumor antigen [Tag] (CpG-NP-Tag) was manufactured and tested in vivo using a syngeneic mouse mammary tumor model following intranasal delivery. We found that our nasal nano-vaccine (CpG-NP-Tag), compared to control NPs administered after primary mammary tumor resection, significantly reduced lung metastasis in female BALB/c mice subjected to surgery (surgery mice). An evaluation of vaccine efficacy in both surgery and non-surgery mice revealed that primary tumor resection reduces CD11b+ monocyte-derived suppressor-like cell accumulation in the lungs, allowing increased infiltration of vaccine-elicited T cells (IFN-γ CD8+ T cells) in the lungs of surgery mice compared to non-surgery mice. These findings suggest that the combination of the target delivery of a nasal vaccine in conjunction with the standard surgery of primary tumors is a plausible adjunctive treatment against the establishment of lung metastasis.

Comparison of the Effectiveness of Four Commercial DNA Extraction Kits on Fresh and Frozen Human Milk Samples.

For-profit donor human milk organizations have DNA-based proprietary methodology for testing incoming milk for adulteration with other species' milk. However, there is currently no standardized methodology for extracting DNA from human milk. Microbiome research has shown that DNA purity and quantity can vary depending on the extraction methodology and storage conditions. This study assessed the purity and quantity of DNA extracted from four commercially available DNA extraction kits-including one kit that was developed for human milk. This study was for method validation only. One donor provided a 90 mL human milk sample. The sample was aliquoted into 70 × 1 mL microcentrifuge tubes. Aliquots were randomized into one of three categories: fresh extraction, extraction after freezing, and extraction after purification and storage at room temperature. DNA was analyzed for purity and quantity using a NanoDrop Spectrophotometer. Results confirmed differences in DNA purity and quantity between extraction kits. The Plasma/Serum Circulating DNA Purification Mini Kit (Norgen Biotek, ON, Canada) provided significantly more DNA, and consistent purity as measured by 260/280 and 260/230 ratios. DNA quantity and purity were similar between fresh and frozen human milk samples. These results suggest that DNA purity and quantity is highest and most consistent when extracted from human milk using the Plasma/Serum Circulating DNA Purification Mini Kit amongst the kits tested in this study. Standardized methodology for extracting DNA from human milk is necessary for improvement of research in the field of human milk. To do this, future studies are recommended for optimization of DNA extraction from human milk using larger sample sizes and multiple donor parents.

A Novel Technique for Securing a Bolster For Skin Grafting after Extensive Vulvar Resection.

Patients with stage III hidradenitis suppurativa of the vulva and adjacent areas, unresponsive to other therapies, may require extensive surgeries. These include excision of diseased areas on the buttocks, vulva, groins, and abdomen, followed by delayed skin grafting. Negative pressure wound therapy has been used over grafts, but it can be difficult to maintain a seal when extensive areas have been resected. We present a novel technique to bolster skin grafts for optimal success. A total vulvectomy and resection of the buttocks, groins, and abdomen are first performed for stage III HS, incorporating all diseased tissue. Negative pressure wound therapy is applied and changed on postoperative day 3-4. On postoperative day 7, split-thickness skin grafts are applied. The skin grafts are covered by Adaptic gauze (3M Company, Minn.), cotton, and a layer of Reston foam (3M Company, St. Paul, Minn.) which is cut to fit the size of the wound. Ostomy skin barriers (Hollister Incorporated, Libertyville, Ill.) are placed on the skin surrounding the excised areas. Pediatric Foley catheters are then placed through the ostomy skin barriers and tied together to prevent movement of the bolster. The use of ostomy skin barriers and pediatric Foley catheters to secure bolsters has not previously been described. We demonstrate a well-tolerated technique, using common surgical supplies, to provide consistent uniform pressure over the graft site. This technique also allows for easy bedside dressing change(s) when indicated.

Physically active learning in preschoolers: Improved self-regulation, comparable quantity estimation.

BACKGROUND: Providing physical activity during the school day may mitigate increasingly sedentary lifestyles among children. Young children may be susceptible to interference during learning and consolidation when performing physical activity concurrently with academic instruction. METHODS: Preschoolers (N = 72, mean age 5.1 ± 0.8 years, 50% female) completed a quantity estimation task before, following, and one week after engaging in either a 20-min physically active or sedentary lesson. Physical activity intensity and volume were measured using heart rate and pedometer step counts, respectively. Off-task behavior was recorded prior to and following the lesson. RESULTS: Children exhibited similar learning and retention, but an added benefit of physically active lessons was a 1900% step increase and a 58% reduction in off-task behavior. CONCLUSION: Providing physically active lessons instead of sitting for extended periods of time in early childhood classrooms reduces sedentary behavior and improves self-regulation while not interfering with educational outcomes.

Expanding the Morphologic, Immunohistochemical, and HPV Genotypic Features of High-grade Squamous Intraepithelial Lesions of the Vulva With Morphology Mimicking Differentiated Vulvar Intraepithelial Neoplasia and/or Lichen Sclerosus.

Squamous cell carcinoma of the vulva can arise through 2 pathways: human papillomavirus (HPV)-dependent high-grade squamous intraepithelial lesions (previously termed usual vulvar intraepithelial neoplasia) or HPV-independent (differentiated vulvar intraepithelial neoplasia, dVIN). Distinguishing between the 2 types can be clinically and histologically difficult. A subset of high-grade squamous intraepithelial lesions with superimposed chronic inflammation mimicking dVIN has recently been reported; p53 shows characteristic mid-epithelial staining (with basal sparing) in such cases. The pathology databases of 2 academic institutions were searched for vulva specimens with corresponding p53 and p16 immunohistochemical stains, yielding 38 specimens (from 27 patients). In situ hybridization and multiplex polymerase chain reaction-MassArray for high-risk HPV were performed on at least 1 block from each patient. All cases resembled dVIN or lichen sclerosus morphologically, but with a higher degree of atypia. All but 1 case demonstrated mid-epithelial p53 staining with basal sparing by immunohistochemistry. All cases showed block positivity for p16 and at least patchy positivity by HPV in situ hybridization. Of the 23 cases with valid HPV DNA polymerase chain reaction results, 15 were positive and 8 were negative. Of the positive cases, HPV16 was identified in 10 cases, with other high-risk types in the remaining 5. To our knowledge, this is the largest cohort of high-grade squamous intraepithelial lesions mimicking dVIN reported to date. Prior studies reported positivity for HPV16 in all cases tested, however, we found HPV16 in only 67% of HPV positive cases. This case series highlights the importance of immunohistochemistry, and occasionally HPV in situ hybridization, for accurate diagnosis, and expands the spectrum of associated HPV types.

Revisiting the remember-know task: Replications of Gardiner and Java (1990).

One of the most evidential behavioral results for two memory processes comes from Gardiner and Java (Memory & Cognition, 18, 23-30 1990). Participants provided more "remember" than "know" responses for old words but more know than remember responses for old nonwords. Moreover, there was no effect of word/nonword status for new items. The combination of a crossover interaction for old items with an invariance for new items provides strong evidence for two distinct processes while ruling out criteria or bias explanations. Here, we report a modern replication of this study. In three experiments, (Experiments 1, 2, and 4) with larger numbers of items and participants, we were unable to replicate the crossover. Instead, our data are more consistent with a single-process account. In a fourth experiment (Experiment 3), we were able to replicate Gardiner and Java's baseline results with a sure-unsure paradigm supporting a single-process explanation. It seems that Gardiner and Java's remarkable crossover result is not replicable.

Vulvar pseudotumoral acyclovir-resistant herpes in an HIV-negative, non-immunosuppressed patient: A therapeutic challenge.

BACKGROUND: Vulvar pseudotumoral herpes infections have been reported in HIV-positive patients. A 32-year-old HIV-negative woman presented with a 6-month history of a vulvar pseudotumor that had been unresponsive to oral acyclovir and valacyclovir, as well as topical imiquimod. OBJECTIVE: This study aimed to evaluate the therapeutic efficacy of a multidrug regimen for vulvar pseudotumor herpes infection in an HIV-negative patient. METHODS: Histology revealed multinucleated giant cells, consistent with a herpes infection. The patient's herpes simplex virus type 2 was resistant to acyclovir. Immunomodulatory agents (thalidomide and topical imiquimod) were started. RESULTS: The lesion enlarged after 6 weeks of treatment. Topical cidofovir 1% gel was added. There was gradual decrease in the pseudotumor size. After 7 months, the Pseudotumor had resolved. CONCLUSION: This is the first reported case of vulvar pseudotumoral herpes in an immunocompetent, HIV-negative patient. Oral thalidomide, in association with topical imiquimod and topical cidofovir, was effective in treating acyclovir-resistant pseudotumoral herpes of the vulva.

Association Between Vulvar Squamous Intraepithelial Lesions and Psychiatric Illness.

OBJECTIVES: The aims of the study were to describe and to compare demographics and the prevalence of psychiatric disorders among patients with low- and high-grade vulvar squamous intraepithelial lesions. METHODS: A retrospective chart review was performed for patients presenting to a vulvar diseases clinic between 1996 and 2019 (N = 2,462). Intake questionnaire data were entered into a deidentified database. Results were compared between 80 patients with biopsy-confirmed high-grade squamous intraepithelial lesions (HSILs) and 48 patients with biopsy-confirmed low-grade squamous intraepithelial lesions (LSILs). Bivariate analysis was performed to compare demographics and psychiatric treatment and outcomes across HSIL and LSIL groups. RESULTS: Among 128 patients with vulvar disease, 80 (62.5%) had HSILs and 48 (37.5%) had LSILs. Patients with HSILs were significantly older (HSIL median [interquartile range] = 49.0 (39.0-61.0) vs LSIL = 36.0 [29.0-53.0], p = .006). There were no significant differences between groups across race/ethnicity, education, marital status, or self-reported household income categories. Forty percent of HSIL patients reported depression compared with 20.8% of LSIL patients (p = .03), whereas 31.3% of HSIL patients and 8.3% of LSIL patients reported anxiety (p = .002). Bipolar disorder was reported in 3.8% of HSIL patients and no LSIL patients (p = .29). There were no differences in the proportion of patients receiving psychiatric counseling, medications, or hospitalizations between groups. CONCLUSIONS: Squamous intraepithelial lesions of the vulva are associated with psychiatric disorders above age-matched national averages; these disorders are more prominent in the HSIL group. Combining mental health services with ongoing disease treatment seem to be part of a comprehensive approach to caring for this patient population.

The prevalence of self-reported medical comorbidities in patients with vulvar lichen sclerosus: A single-center retrospective study.

OBJECTIVE: To compare the demographics and self-reported medical comorbidities of patients with vulvar lichen sclerosus (VLS) with those of women with other vulvar conditions. METHODS: Intake questionnaires for patients presenting to the University of Michigan Center for Vulvar Diseases between 1996 and 2019 were entered into a de-identified database (n = 1983). Responses to questions about thyroid disease, urinary symptoms and signs, gastrointestinal conditions, and pain conditions were collected. RESULTS: A total of 1983 women, including 865 patients with VLS and 1118 patients without VLS were enrolled. Pearson's χ2 analysis showed that age, hypertension, anorectal fissures, peptic ulcer disease/gastroesophageal reflux disease, urinary incontinence, fibromyalgia, thyroid disease, kidney problems, liver problems, and cancer were significantly associated with VLS when compared between the VLS and non-VLS groups (P < 0.01). However, multiple regression analysis demonstrated that only age, thyroid disease, and anorectal fissures were strongly associated with VLS (P < 0.01). CONCLUSION: Increasing age, thyroid disease, and anorectal fissures were significantly associated with VLS. The association between anorectal fissures and VLS likely represents a sequela of the disease rather than a true comorbidity.