Understanding the Role of Regulators of Homologous Recombination

DNA double strand breaks (DSB) are the most genotoxic lesions because they affect the integrity of the genome. DSBs can be caused by exogenous factors such as ionizing radiation or induced during meiosis. Failure to repair DSBs can cause genome instability, cancer and cell death. DSBs can be repaired by one of three main pathways, homologous recombination (HR), non-homologous end joining (NHEJ) and microhomology mediated end joining (MMEJ). NHEJ and MMEJ are error-prone but HR is relatively error-free since it relies on a homologous DNA sequence. Studies have shown that HR accounts for repair of about 50% of induced DSBs. HR is also essential for proper segregation of chromosomes and telomere maintenance in eukaryotes. Impaired HR is implicated in diseases like Bloom’s syndrome, Fanconi’s anemia and breast and ovarian cancer. In eukaryotes, the mechanism of HR is largely governed by two recombinases, Rad51 and Dmc1, the homologs of E. coli RecA. Dmc1 is meiosis-specific whereas Rad51 functions in mitosis and meiosis. Rad51 and Dmc1 mediate ATP-dependent DNA strand exchange and require recombination mediators and accessory factors to assist them in forming a presynaptic filament on single-stranded DNA and search for homology. This study involved examining the biochemical properties of a set of proteins with respect to their function in RAD51-mediated homologous recombination. The results indicated that HELLS, BCCIPα and BCCIPβ interact with RAD51 and bind single-stranded DNA. Further, these proteins function in HR by stabilizing the RAD51 presynaptic filament and preventing it from dissociation, thus promoting efficient recombination

The Shadows of Life: Medicaid\u27s Failure of Health Care\u27s Moral Test

North Carolina Medicaid covers one-fifth of the state’s population and makes up approximately one-third of the budget. Yet the state has experienced increasing costs and worsening health outcomes over the past decade, while socioeconomic disparities persist among communities. In this article, the authors explore the factors that influence these trends and provide a series of policy lessons to inform the state’s current reform efforts following the recent approval of North Carolina’s Section 1115 waiver by the Centers for Medicare and Medicaid Services. The authors used health, social, and financial data from the state Department of Health and Human Services, the Robert Wood Johnson Foundation, and the University of North Carolina to identify the highest cost counties in North Carolina. They found higher per beneficiary spending to be inversely related to population health, with many counties with the most expensive beneficiaries also reporting poor health outcomes. These trends appear to be attributed to a breakdown in access to basic health services, with high cost counties often lacking adequate numbers of health care providers and possessing limited health care services, leading patients to primarily engage the health care system in a reactive manner and predominantly in institutional care settings. To illustrate this pattern, the authors developed case studies of Tyrrell County and Graham County, which respectively are home to the state’s worst health outcomes and most expensive Medicaid beneficiaries. The authors combined stories of these counties with the larger historical trends to offer policy recommendations to help reorient North Carolina Medicaid around patient needs. The results shed light on traditionally understudied hotspots of cost and poor outcomes in North Carolina, while proposing tangible steps to support reform

Blue Bell Listeria Outbreak from 2013-2015

This paper won a first place writing flag award in the collaborative category. Shivani Shah and Henykumari Patel, writing for D’Arcy Randall 's CHE 333T course, "Engineering Communication".Randall, D'ArcyUndergraduate Studie

Predicting subsequent contralateral slipped capital femoral epiphysis: an evidence-based approach.

PurposeThe purpose of this study was to identify risk factors for developing a subsequent contralateral slipped capital femoral epiphysis (SCFE) and provide a prediction score to quantify risk of subsequent slip at the time of initial presentation.MethodsThis retrospective study included patients that presented with a unilateral SCFE between 2006 and 2017. Chart and radiographic review were performed to collect demographic, clinical and radiographic risk factors. Descriptive statistics, univariate analyses and multivariate regression analysis were used to compare risk factors between patients that did or did not develop a subsequent contralateral SCFE.ResultsThis study included 183 patients and 33 patients (18%) developed a subsequent contralateral SCFE. Younger age at time of initial presentation, lower modified Oxford Score and smaller difference in epiphyseal-diaphyseal angle between both sides during index presentation were significant predictors of subsequent contralateral SCFE. Specifically, age ≤ 11 years, modified Oxford Score ≤ 20 and difference in epiphyseal-diaphyseal angle of ≤ 21° between both hips were predictive of a contralateral slip (Area Under the Curve = 0.78; p < 0.05). The presence of each risk factor increased the risk of subsequent contralateral SCFE and having all three risk factors increased the risk to 73%.ConclusionThere is a significant risk of subsequent contralateral SCFE in patients with unilateral SCFE, and predictive risk factors include younger age, lower modified Oxford Score and smaller difference in epiphyseal-diaphyseal angle between the affected and unaffected hips.Level of evidenceLevel III

HD 4915: A Maunder Minimum Candidate

We study the magnetic activity cycle of HD 4915 using the \ion{Ca}{2} H \& K emission line strengths measured by Keck I/HIRES spectrograph. The star has been observed as a part of California Planet Search Program from 2006 to present. We note decreasing amplitude in the magnetic activity cycle, a pattern suggesting the star's entry into a Magnetic Grand Minimum (MGM) state, reminiscent of the Sun's Maunder and Dalton Minima. We recommend further monitoring of the star to confirm the grand minimum nature of the dynamo, which would provide insight into the state of the Sun's chromosphere and the global magnetic field during its grand minima. We also recommend continued observations of H \& K emission lines, and ground or space based photometric observations to estimate the sunspot coverage.Comment: To be submitted to AAS Journals; comments welcom

ReGAE 5: Can we improve the surgical journey for African-Caribbean patients undergoing glaucoma filtration surgery? Some preliminary findings

Vinette Cross, Peter Shah, Martin Glynn, Shivani ChidrawarCentre for Health and Social Care Improvement, University of Wolverhampton, Wolverhampton, United KingdomAim: To explore the experiences of African-Caribbean patients who had undergone filtration surgery for advanced glaucoma.Methods: Semi-structured qualitative interviews were used to collect the data and an interview guide was developed. Participants recounted when they first became aware of a problem with their eyes and their feelings at the time. Subsequently they were probed about their subjective experiences of becoming a glaucoma patient, receiving treatment, the decision to undergo surgery, and its aftermath. The perceptions of three participants from three different generations of African-Caribbean men were selected from the larger study for presentation in this paper. Interview transcripts were subjected to narrative analysis.Results: The concept of patient-partnership was re-framed in terms of mentorship. Surgeon–patient relationships are central to developing effective coping strategies. Support to face the ordeals ahead, challenge to take on new responsibilities, and help to envision a meaningful life with glaucoma are fundamental to fostering trust and maintaining motivation to continue.Conclusions: The use of patient narratives provides a valuable a resource for enhancing communication skills and patient-centered care in the hospital eye service.Keywords: glaucoma, secondary eye-care, African-Caribbean, filtration surgery, trabeculectom

Modified mattress sutures vs running sutures in uterine closure: which is better?

Background: Conventional closure of uterus has been known to bear risk of scar dehiscence and scar rupture in subsequent pregnancies and thus, a study was conducted to compare the outcome of uterine closure with modified mattress manner and running manner and to establish a better method of uterine closure during caesarean section. Objective was to compare the conventional single layer running sutures and single layer modified mattress sutures for closure of uterus in caesarean section and find out which method is superior.Methods: This prospective interventional study was carried out in Dhiraj Hospital, a tertiary care hospital in Vadodara. 60 pregnant women in the study criteria were equally divided randomly into 2 groups. Uterine closure was done in single layered sutures, one by running sutures and other group by modified mattress sutures.Results: Uterine scar thickness on 8th day and 6 months post-operatively was significantly more in single layered suturing by modified mattress suture compared to running suture (p <0.05).Conclusions: Uterine closure by single layered modified mattress suture is better in comparison to conventional single layer running suture

Engineering CHO cell lines for the production of biosimilars of murine cell derived reference products

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Colectomy averted: A successful case report of Fidaxomicin administration through a loop ileostomy for fulminant, Clostridioides difficile infection

Clostridioides difficile infection is considered an urgent public health threat by the Centers for Disease Control and Prevention. Recent practice guidelines recommend either vancomycin or fidaxomicin for an initial episode of C. difficile infection and further recommend a subtotal colectomy in severe cases. There are limited data discussing novel approaches for fidaxomicin administration in severe C. difficile infection to avert colectomy. We describe an off-label route of fidaxomicin administration through a loop ileostomy twice daily with successful outcome

The role of foetal assessment by ultrasound at 11-13+6 weeks of gestation

Background: The prevalence of congenital anomalies has been increasing over the years, and it is estimated that every year 1 in 33 infants are affected by some sort of congenital anomaly. At 12 weeks of intrauterine gestation, most of the major foetal structures complete their development and also proper delineation of the foetal anatomy is possible by the time of routine NT scan at 11-13+6 weeks. Methods: This was a prospective study of 110 cases who underwent a first trimester 11-13+6 weeks scan for congenital foetal abnormalities. The eligibility criteria for selection of cases were first trimester pregnancy between the 11-13+6 weeks gestation and CRL between 45 mm and 84 mm. Results: The study found that the detection rate of foetus abnormalities was 15.4% in mothers over 35 years old. Total 2.7% of the present study population were detected to be high risk for trisomy 21. All the 110 cases in present study were followed up till delivery/ termination. MTP was performed in 8.1% cases with lethal anomalies and in 1 cases of structural anomaly with missed abortion, D and E was done. 91% delivered live and healthy babies. There was no intrauterine foetal death or still born in present study. Conclusions: Ultrasound at 11-13+6 weeks must be mandatory, not only for the detection of major foetal anomalies but also for diagnosis of multiple pregnancy and abnormal pregnancy like missed abortion, molar pregnancy and ectopic pregnancy