Bowlesaldridge1104
Senescence is a tumor suppressor response that prevents the proliferation of mutated cells and alert the immune system for their elimination. However, this program is not perfect and with time additional genetic and epigenetic changes can impair tumor suppression and promote cancer progression both in cell autonomous and non-cell autonomous manners. A polyploid barrier is implemented in senescent cells to further prevent cell expansion but polyploid cells can generate highly malignant tumor cells via de-polyploidization. The nuclear lamina can act as an additional fail safe to prevent cancer in these cells and drugs able to stabilize the nuclear lamina may help to treat cancers by preventing senescence escape.Microglia are immune cells of the central nervous system capable of distinct phenotypic changes and migration in response to injury. These changes most notably include the retraction of fine dendritic structures and adoption of a globular, phagocytic morphology. Due to their characteristic responses, microglia frequently act as histological indicators of injury progression. While algorithms seeking to automate microglia counts and morphological analysis are becoming increasingly popular, few exist that are adequate for use within the retina and manual analysis remains prevalent. To address this, we propose a novel segmentation routine, implemented within FIJI-ImageJ, to perform automated segmentation and cell counting of retinal microglia. We show that our routine could perform cell counts with accuracy similar to manual observers using the I307N Rho model. Tracking cell position relative to retinal vasculature, we observed population migration towards the photoreceptor layer beginning 12 h post light damage. Using feature selection with Chi2 and principal component analysis, we resolved cells along a morphological gradient, demonstrating that extracted features were sufficiently descriptive to capture subtle morphological changes within cell populations in I307N Rho and Balb/c TLR2-/- retinal degeneration models. Birinapant research buy Taken together, we introduce a novel automated routine capable of efficient image processing and segmentation. Using data retrieved following segmentation, we perform morphological analysis simultaneously on whole populations of cells, rather than individually. Our algorithm was built entirely with open-source software, for use on retinal microglia.
For research on circadian intraocular pressure (IOP), rebound tonometers are widely used with or without general anesthesia as a non-invasive approach to obtain IOP values. However, whether general anesthesia such as inhalation anesthesia with isoflurane affects the circadian rhythm of IOP and in turn IOP measurements is currently unclear. As such, data reporting IOP values obtained under general anesthesia should be interpreted with caution. The purpose of this study was to evaluate how general anesthesia with isoflurane inhalation affects the circadian rhythm of IOP.
C57Bl/6J strain mice maintained using a 12h12h light/dark cycle (lights on and off at ZT0 and ZT12, respectively) were used. IOPs were measured using a rebound tonometer (Icare TonoLab) before and 3, 5, 10, 15, and 30min after initiating anesthesia in both light and dark phases (ZT 2-6 and ZT 14-18, respectively). Awake IOPs and IOPs at 3 and 5min after anesthesia initiation were also obtained at ZT5, 8, 11, 14, 17, and 20 to assess IOP diuul to monitor the circadian rhythm of IOP in mice.
Both awake and anesthetized mice demonstrated a robust circadian rhythm for IOP. Murine IOP showed similar gradual decreases under inhalation anesthesia with isoflurane in both the light and dark phases. IOPs measured using a rebound tonometer within 3 min of initiating isoflurane anesthesia were comparable to awake IOPs, and thus may be useful to monitor the circadian rhythm of IOP in mice.Microbial keratitis is an infectious disease of the eye, in which the cornea is inflamed. Under severe conditions, keratitis can lead to significant loss of vision and enucleation of the eye. Ocular trauma is the major risk factor causing keratitis and microorganisms viz., bacteria, fungi, viruses are the causative agents. The current study characterized the conjunctival bacterial microbiomes of healthy individuals and individuals with bacterial keratitis (BK) and assessed whether ocular microbiome dysbiosis is prevalent in BK patients. Ocular bacterial microbiomes were generated from the conjunctival swabs of healthy controls (HC-SW) and conjunctival swabs (BK-SW) and corneal scrapings (BK-CR) of BK patients using V3-V4 amplicon sequencing and data analysed using QIIME and R software. The Alpha diversity indices, diversity and abundance of different phyla and genera, heat map analysis, NMDS plots and inferred functional pathway analysis clearly discriminated the bacterial microbiomes of conjunctival swabs of healthy controls from that of BK patients. Preponderance of negative interactions in the hub genera were observed in BK-CR and BK-SW compared to HC-SW. In addition, a consistent increase in the abundance of pathogenic bacteria, as inferred from published literature, was observed in the conjunctiva of BK patients compared to HC and this may be related to causing or exacerbating ocular surface inflammation. This is the first study demonstrating dysbiosis in the ocular bacterial microbiome of conjunctiva of bacterial keratitis patients compared to the eye of healthy controls. The bacterial microbiome associated with the corneal scrapings of keratitis individuals is also described for the first time.
Permanent contraception has historically been more prevalent among non-White women with lower education and income. Given increasing popularity of long-acting reversible contraception (LARC), we examine changing sociodemographic patterns of permanent contraception and LARC.
We performed a descriptive analysis of the National Survey of Family Growth (NSFG) from 2006 to 2017, with multivariable analyses of the 2006 to 2010 and 2015 to 2017 cohorts. Using multinomial logistic regression, we investigate predictors of contraceptive category (permanent contraception vs LARC, lower-efficacy contraception vs LARC) in reproductive-aged women.
Total 8161 respondents were included in 2 distinct but analogous regression analyses (1) the most recent survey cohort, 2015 to 2017 and (2) the cohort a decade prior, 2006 to 2010. Over this period, the prevalence of LARC increased nearly 3-fold (6.2%-16.7%), while permanent contraception use trended downwards (22%-18.6%). Yet, in adjusted models, we observed little changeo chooses permanent contraception, with urban, educated, higher income women more likely to use LARC. Ongoing efforts are needed to understand and reduce economic barriers to LARC.
Comparing 2006-2010 to 2015-2017, reliance on female permanent contraception decreased while LARC use increased, making prevalence more similar. However, significant socioeconomic differences persist in who chooses permanent contraception, with urban, educated, higher income women more likely to use LARC. Ongoing efforts are needed to understand and reduce economic barriers to LARC.
This study examines receipt of formal sex education as a potential mechanism that may explain the observed associations between disability status and contraceptive use among young women with disabilities.
Using the 2011-2017 National Survey of Family Growth, we analyzed data from 2861 women aged 18 to 24 years, who experienced voluntary first sexual intercourse with a male partner. Women whose first intercourse was involuntary (7% of all women reporting sexual intercourse) were excluded from the analytic sample. Mediation analysis was used to estimate the indirect effect of receipt of formal sex education before first sexual intercourse on the association between disability status and contraceptive use at first intercourse.
Compared to nondisabled women, women with cognitive disabilities were less likely to report receipt of instruction in each of 6 discrete formal sex education topics and received instruction on a fewer number of topics overall (B=-0.286, 95% CI=-0.426 to -0.147), prior to first voluntary intercourse. In turn, the greater number of topics received predicted an increased likelihood of contraceptive use at first voluntary intercourse among these women (B=0.188, 95% CI=0.055-0.321). No significant association between noncognitive disabilities and receipt of formal sex education or contraceptive use at first intercourse was observed.
Given the positive association between formal sex education and contraceptive use among young adult women with and without disabilities, ongoing efforts to increase access to formal sex education are needed. Special attention is needed for those women with cognitive disabilities.
Given the positive association between formal sex education and contraceptive use among young adult women with and without disabilities, ongoing efforts to increase access to formal sex education are needed. Special attention is needed for those women with cognitive disabilities.
Telemedicine for medication abortion (teleMAB) is safe and effective, yet little is known about how its introduction affects service delivery. We assessed changes in service delivery patterns 1 year after introducing teleMAB at Planned Parenthood in 2 U.S. states.
Retrospective records analysis using electronic health record data from Planned Parenthood health centers in Montana and Nevada from 2015 to 2018. We included all patients receiving medication or aspiration abortion in the year before and after introducing site-to-site teleMAB. Outcomes included the proportion of medication abortions (vs. aspiration); gestational age at abortion; time to appointment; and distance traveled. We compared outcomes pre- and postimplementation using χ
, t tests, and Mann-Whitney U tests.
We analyzed data for 3,038 abortions 1,314 pre- and 1,724 postimplementation. In Montana, the proportion of medication abortions increased postimplementation (60% vs. 65%, p=0.04). Mean gestational age was similar 58 versus 57 dayscess to medication abortion and should be taken to scale where feasible. Continued efforts are needed to mitigate or reverse policy restrictions on telemedicine for medication abortion.Primary cardiac tumor can arise from any location in the right and left cardiac chamber. Complete excision is generally recommended due to uncertainty regarding malignancy; however, it is important to minimize the resultant functional deterioration after surgery. We have reported a case of endocardial hemangioma (4x3x3 cm) on the free wall of the right ventricle, located between the anterior and posterior papillary muscles. We have described details of the procedure to preserve the right ventricular volume and competence of the tricuspid valve.Reconstruction of extensive chest wall defects is challenging in young children. Rigid prosthetic plates, designed to prevent paradoxical respiration, do not grow with the child and may result in progressive chest and spinal deformity. Also, because of the greater proportionate size of the thorax relative to the limbs in young children, extra-thoracic soft tissue flaps may be too small for an adequate reconstruction. Here, we report reconstruction of a large chest wall defect following resection of a Ewing's sarcoma in a two-year-old boy, using Permacol® membrane supported by a diagonally translocated seventh rib and covered by a latissimus dorsi flap.
