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To define the prevalence of medical eye disease diagnoses among children enrolled in commercial insurance plans in the United States and to evaluate differences among groups based on the US census region, race/ethnicity, and familial net worth.: Retrospective study of de-identified claims data from the OptumLab® Data Warehouse (OLDW) between 2007 and 2018. All children (19 years) in the OLDW with coverage were studied and those with a claim for a significant eye disease (strabismus, amblyopia, nystagmus or structural eye disorders) with minimum 6-months follow-up were studied. Baseline characteristics were extracted for the calculation of eye disease prevalence, including age, sex, race/ethnicity, region of residence, and family net worth. The prevalence of each type of eye disease was calculated among all children and by baseline characteristics.: 10,759,066 children met the study criteria. The presence of any significant eye diagnosis was 6.7%. Disease was diagnosed more often in whites (6.9%) than blacks (5.6%) and Hispanics (5.9%). The most common eye disease diagnosed was strabismus (3.2%) followed by amblyopia (1.5%). In the North-East region, there was a 10.6% prevalence of any significant eye disease diagnosis, whereas in the Mid-West, it was 7.4% followed by the South and West (5.9% and 5.3%, respectively) (: Diagnosis of significant eye diseases is relatively common in American children. The most common medical eye disease diagnosis is strabismus. Prevalence of eye disease diagnosis from claims data varies between geographical regions and different income groups. This may reflect differences in healthcare utilization rather than true disease prevalence.

BackgroundThe true prevalence of low sexual desire among women is disputed among researchers due to the complex nature and presentation of women’s sexual problems.AimTo qualitatively analyze the aspects of libido/sexual desire frequently discussed by Reddit users and compare them with the current understanding of female sexual well-being and sexual desire disorders.MethodsBy using the Reddit application programming interface, the TwoXChromosomes subreddit was queried for posts with the keywords libido and sex drive. Posts that were deleted or unrelated to themes of libido/sex drive were excluded. A total of 85 threads—63 queried from the keyword libido and 22 from sex drive—and approximately 2900 comments were qualitatively analyzed per the grounded theory approach. Five independent researchers read and coded each thread to identify dominant themes and emergent concepts.OutcomesOutcomes of interest included codes related to sexual dysfunction, libido, orgasm, masturbation, types of sex, psychology, relationships, intimacy, treatment, medications, and health care.ResultsPosters were primarily heterosexual women in their 20s and 30s. The code categories with the highest frequency were relationships (22.7%, n = 272), libido (22.2%, n = 210), psychological (20.2%, n = 191), medications (7.29%, n = 69), and intimacy (6.0%, n = 57). Users frequently described a decrease in libido secondary to medications, particularly antidepressants and hormonal birth control. Many users discussed the challenges of navigating a relationship with low sexual desire and the resulting sexual distress. Posters described feelings of sadness, anxiety, and guilt due to their low desire. Additionally, users discussed the role that sex plays in relationships, whether as a way to develop intimacy between partners or to achieve orgasm. Finally, posters expressed dissatisfaction with health care addressing their concerns surrounding sexual desire.Clinical ImplicationsThe study findings—namely, the impact of medications on sexual health, the interaction of sexual desire and mental health, and cited examples of inadequate sexual health care—can help guide sexual well-being research, diagnosis, and public policy.Strengths and LimitationsUsing Reddit as a data source allowed for the analysis of women’s experiences outside the preestablished concepts of female sexual desire. Limitations to the study include the potential for posts to be deleted by moderator guidelines, the young demographic distribution of Reddit users, and the popularity-based structure of subreddit threads.ConclusionOur results emphasize the psychosocial aspects of sexual desire and the need to redefine sexual problems to encompass the complex nature of female sexual well-being.

Coronavirus disease (COVID)-related misinformation is prevalent online, including on social media. The purpose of this study was to explore factors associated with user engagement with COVID-related misinformation on the social media platform, TikTok. A sample of TikTok videos associated with the hashtag #coronavirus was downloaded on September 20, 2020. Misinformation was evaluated on a scale (low, medium, and high) using a codebook developed by experts in infectious diseases. Multivariable modeling was used to evaluate factors associated with number of views and presence of user comments indicating intention to change behavior. One hundred and sixty-six TikTok videos were identified and reviewed. Moderate misinformation was present in 36 (22%) videos viewed a median of 6.8 million times (interquartile range [IQR] 3.6–16 million), and high-level misinformation was present in 11 (7%) videos viewed a median of 9.4 million times (IQR 5.1–18 million). After controlling for characteristics and content, videos containing moderate misinformation were less likely to generate a user response indicating intended behavior change. By contrast, videos containing high-level misinformation were less likely to be viewed but demonstrated a nonsignificant trend towards higher engagement among viewers. COVID-related misinformation is less frequently viewed on TikTok but more likely to engage viewers. Public health authorities can combat misinformation on social media by posting informative content of their own.

Describe patient-reported pain and function within 24 months of a pelvic fracture treated with posterior screw fixation and identify factors associated with increased pain.Prospective case series.Academic trauma center.Eighty-eight patients with adult pelvic fracture treated with sacroiliac or transiliac screws.Average pain measured with the Brief Pain Inventory (BPI); function measured with the Majeed Pelvic Outcome Score from 6 to 24 months postinjury.The mean pain from 6 to 24 months postinjury was 2.22 on the 10-point BPI scale (95% CI, 0.64-3.81). Sixty-nine patients (78.4%) reported mild to no pain at 6 months; 12 (13.6%) patients had severe pain. Two years after injury, 71 patients (80.6%) exhibited mild to no pain. Within 24 months of injury, the mean pelvic function was 71 on the 100-point Majeed scale (95% CI, 60-82). Half of the sample (n = 44) had good to excellent pelvis function by 6 months postinjury; 55 patients (62.5%) attained this level of function by 24 months. A history of chronic pain (1.31; 95% CI, 0.26-2.37; P = 0.02), initial fracture displacement (≥5 mm) (0.99; 95% CI, 0.23-1.69; P = 0.01), and socioeconomic deprivation (0.28; 95% CI, 0.11-0.44; P0.01) were significantly associated with increased pain.Our findings suggest that most patients with unstable pelvic ring fractures treated with posterior screw fixation achieve minimal to no pelvis pain and good to excellent pelvic function 6-24 months after injury.Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Background The hybridizing field crickets, Gryllus firmus and Gryllus pennsylvanicus have several barriers that prevent gene flow between species. The behavioral pre-zygotic mating barrier, where males court conspecifics more intensely than heterospecifics, is important because by acting earlier in the life cycle it has the potential to prevent a larger fraction of hybridization. The mechanism behind such male mate preference is unknown. Here we investigate if the female cuticular hydrocarbon (CHC) profile could be the signal behind male courtship. Results While males of the two species display nearly identical CHC profiles, females have different, albeit overlapping profiles and some females (between 15 and 45%) of both species display a male-like profile distinct from profiles of typical females. We classified CHC females profile into three categories: G. firmus-like (F; including mainly G. firmus females), G. pennsylvanicus-like (P; including mainly G. pennsylvanicus females), and male-like (ML; including females of both species). Gryllus firmus males courted ML and F females more often and faster than they courted P females (p Gryllus pennsylvanicus males were slower to court than G. firmus males, but courted ML females more often (p p G. firmus males). Conclusions Our results suggest that male mate preference is at least partially informed by female CHC profile and that ML females elicit high courtship behavior in both species. Since ML females exist in both species and are preferred over other heterospecific females, it is likely that this female type is responsible for most hybrid offspring production.

Since their development, dental implants have become one of the most common procedures to rehabilitate patients with single missing teeth or fully edentulous jaws. As implants become more mainstream, determining the factors that affect osseointegration is extremely important. Medical risk factors identified to negatively affect osseointegration include diabetes and osteoporosis. However, other systemic conditions and medications that interfere with wound healing have not been as widely investigated. The aim of this systematic review was to evaluate the effect of systemic disorders including diabetes and osteoporosis on implant osseointegration. The aim was also to evaluate the effect of other diseases, such as neurocognitive diseases, cardiovascular disease, human immunodeficiency virus (HIV), hypothyroidism, rheumatoid arthritis, and medications, such as selective serotonin reuptake inhibitors (SSRIs), proton pump inhibitors (PPIs), and antihypertensives. Although the literature does not demonstrate that diabetes negatively affects implant osseointegration, most studies focus on well-controlled diabetics and the use of prophylactic antibiotics. In addition, studies have shown increased long-term bone and soft tissue complications. For osteoporosis, recent studies and reviews also fail to demonstrate a lower osseointegration rate. However, caution must be exercised in these patients due to the risk for osteonecrosis of the jaws (ONJ), especially in patients with bone malignancies. There is also no direct evidence that patients with HIV, cardiovascular disease, neurologic disorders, hypothyroidism, or rheumatoid arthritis have a decreased rate of implant osseointegration. However, some preliminary evidence suggests that medications such as SSRIs or PPIs may have a negative effect on implant osseointegration. These studies are fairly recent and must be validated with continuous research. Moreover, disease control, concomitant medications, and other comorbidities complicate implant osseointegration and must guide our treatment approaches and clinical guidelines.

Previous studies have shown an association between injury risk and strabismus in aged Medicare beneficiaries and children. The injury prevalence in strabismic children was 30% in a study of10 million patients in the OptumLabs Data Warehouse. The purpose of this study was to determine whether strabismus surgery decreases the risk of injury.Retrospective cohort study.The OptumLabs Data Warehouse is a deidentified, longitudinal health database that was queried for strabismic patients aged19 years. The patients who underwent strabismus surgery were compared with those strabismic patients who did not undergo surgery for injury. Injury risk (fractures, musculoskeletal injuries, and head injuries) during their insurance enrollment was calculated in the nonsurgical patients after their first strabismus claim and compared with the risk in surgical patients postoperatively.There were 344,794 patients with strabismus. Surgery was performed in 26,459 (7.7%). Esotropia was the most common diagnosis (n = 181,195, 52.6%) followed by exotropia (n = 161,712, 46.9%) and hypertropia (n = 43,831, 12.7%). Within these groups, patients with hypertropia were significantly more likely to undergo surgery (24.2%) compared with patients with esotropia and exotropia (10.2% and 9.6%, respectively). Injuries were diagnosed after the first strabismus claim in 94,960 (29.8%) nonsurgical patients vs 5790 (21.9%) postsurgical patients (P.001) with a mean follow-up of 4.3 ± 3.1 vs 3.8 ± 3.1 years, respectively. The adjusted hazard ratio for injuries was 0.85 (95% confidence interval [CI]: 0.83-0.87) for the risk of any injury after strabismus surgery. The hazard ratio was significantly decreased after surgery for each type of strabismus: esotropia (0.91, 95% CI: 0.88-0.94), exotropia (0.82, 95% CI: 0.80-0.85), and hypertropia (0.89, 95% CI: 0.85-0.93).Strabismus surgery was associated with a 15% decrease in the risk of physical injury over approximately 4 years of follow-up. Surgery may be a factor in decreasing injury risk in strabismic patients, particularly in exotropia. Given the large number of children with strabismus in the United States, further assessment of strategies such as strabismus surgery to reduce injuries in children with strabismus is needed.

In the earliest stages of tumor development, epithelial tumors (carcinomas) are physically confined to the area of the tissue in which they form. These nascent lesions (carcinomas in situ) are sequestered from the tissue parenchyma by the basement membrane. Within the tissue parenchyma lie a myriad of cell types comprised of fibroblasts, immune and inflammatory cells and endothelial cells. Upon invasion across the basement membrane and into the tissue parenchyma, tumors must manipulate the expression of pro- and anti-tumorigenic proteins such that pro-tumorigenic factors are produced in excess to anti-tumorigenic proteins. One such anti-tumorigenic protein is Thrombospondin-1 (Tsp-1). We have previously demonstrated that stimulation of Tsp-1 in the tumor microenvironment (TME) potently inhibits tumor growth and progression and in some cases induces tumor regression. Here, we identify a novel tumor-mediated mechanism to repress the expression of Tsp-1 in the TME via secretion of the serine protease PRSS2. We demonstrate that PRSS2 represses Tsp-1, not via its enzymatic activity, but by binding to low-density lipoprotein receptor-related protein 1 (LRP1). These findings describe a novel activity for PRSS2 through binding to LRP1 and represent a potential therapeutic strategy to treat cancer by blocking the PRSS2-mediated repression of Tsp-1.

Current treatment of triple negative breast cancer patients is hindered by a high incidence of chemoresistance (30-50%). The prevailing theory is that resistance and subsequent recurrence is driven by cancer stem cells. Unfortunately, the functional characterization of cancer stem cells at the molecular level is still incomplete. We show here, that within the canonical breast cancer stem cell population, a subset of cells characterized by high Notch1 expression possesses the tumor-initiating property associated with cancer stem cells. Moreover, the tumor initiating property of these high Notch1-expressing breast cancer stem cells is mediated by a cleavage independent Notch signaling pathway culminating in the repression of SIRT1. Of note, the Notch1-mediated repression of SIRT1 is required not only for tumor initiation, but also for chemoresistance in breast cancer stem cells. Strikingly, inhibition of SIRT1 obviates the requirement for Notch1, marking the first example of conferring cancer stem cell function by inhibiting the activity of a single protein. We also demonstrate that progenitor-like mammary epithelial cells, which possess both luminal and basal properties, are also characterized by high Notch1 expression and repression of SIRT1 via the non-canonical pathway. These findings provide the first functional mechanistic requirements for tumor initiation by breast cancer stem cells and suggest that activation of the non-canonical Notch1 pathway is hardwired into tumor-initiating progenitor cells and thus a prerequisite for tumor initiation.Statement of SignificanceWe demonstrate that chemoresistant and tumor-initiating properties of breast cancer stem cells are driven by repression of SIRT1 via non-canonical Notch signaling, suggesting a novel therapeutic strategy for triple negative breast cancer.

IMPORTANCE: For critically ill patients with advanced medical illnesses and poor prognoses, overuse of invasive intensive care unit (ICU) treatments may prolong suffering without benefit. OBJECTIVE: To examine whether use of time-limited trials (TLTs) as the default care-planning approach for critically ill patients with advanced medical illnesses was associated with decreased duration and intensity of nonbeneficial ICU care. DESIGN, SETTING, AND PARTICIPANTS: This prospective quality improvement study was conducted from June 1, 2017, to December 31, 2019, at the medical ICUs of 3 academic public hospitals in California. Patients at risk for nonbeneficial ICU treatments due to advanced medical illnesses were identified using categories from the Society of Critical Care Medicine guidelines for admission and triage. INTERVENTIONS: Clinicians were trained to use TLTs as the default communication and care-planning approach in meetings with family and surrogate decision makers. MAIN OUTCOMES AND MEASURES: Quality of family meetings (process measure) and ICU length of stay (clinical outcome measure). RESULTS: A total of 209 patients were included (mean [SD] age, 63.6 [16.3] years; 127 men [60.8%]; 101 Hispanic patients [48.3%]), with 113 patients (54.1%) in the preintervention period and 96 patients (45.9%) in the postintervention period. Formal family meetings increased from 68 of 113 (60.2%) to 92 of 96 (95.8%) patients between the preintervention and postintervention periods (P

Atropine and patching are standard treatments for amblyopia, but the prevalence of atropine therapy in the United States is unknown. This study used the OptumLabs Data Warehouse to evaluate pharmacy claims for topical atropine to evaluate the frequency of its treatment for amblyopia and to compare demographic factors in cohorts of amblyopic children who were and were not prescribed atropine. Overall, 55.2% of amblyopic children were prescribed atropine more than once. The children who were prescribed atropine had a higher likelihood of living in geographic regions in the South or Midwest.

Current treatment of triple negative breast cancer is hindered by a high incidence of chemoresistance (30-50%). The prevailing theory is that resistance and subsequent recurrence is driven by cancer stem cells. Unfortunately, the functional characterization of cancer stem cells at the molecular level is still incomplete. We show here, that within the canonical breast cancer stem cell population (CD24low/CD44+/ESA+) of triple negative breast cancer cells, a subset of cells characterized by high Notch1 expression possesses the tumor-initiating and chemoresistance properties associated with cancer stem cells. Moreover, the tumor initiating property of these Notch1-high expressing breast cancer stem cells is mediated by the repression of SIRT1. We also demonstrate that Notch1 represses SIRT1 through a non-canonical, cleavage independent pathway via PI3K/Akt/mTORC2. Strikingly, the repression of SIRT1 obviates the requirement for high Notch1 expression. These findings provide the first functional mechanistic requirements for breast cancer stem cell tumor initiation and chemoresistance. Our results also identify a novel non-canonical Notch1 signaling pathway regulating breast cancer stem cell function. We postulate that this pathway can be exploited as a potential therapeutic strategy to eradicate cancer stem cells and reduce the incidence of chemoresistance and recurrence. Citation Format: Lufei Sui, Suming Wang, Danielle Sim, Randolph S. Watnick. Notch1 non-canonical pathway drives breast cancer stem cell function [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4963.