Synergistic Activity of DNA Damage Response Inhibitors in Combination with Radium-223 in Prostate Cancer.

Radium-223 (Ra) and Lutetium-177-labelled-PSMA-617 (Lu-PSMA) are currently the only radiopharmaceutical treatments to prolong survival for patients with metastatic-castration-resistant prostate cancer (mCRPC); however, mCRPC remains an aggressive disease. Recent clinical evidence suggests patients with mutations in DNA repair genes associated with homologous recombination have a greater clinical benefit from Ra. In this study, we aimed to determine the utility of combining DNA damage response (DDR) inhibitors to increase the therapeutic efficacy of X-rays, or Ra.

Behavioral and physiological responses to an inspired-air supplemental cooling system for dairy cows in free-stall housing.

During heat stress, dairy cows spend less time lying down to dissipate heat. Heat stress abatement strategies generally target cows outside of their resting areas. However, cooling cows while in their stalls could help alleviate heat stress without compromising lying behavior.

A survey of Canadian dairy nutritionists to assess current trace element formulation practices.

The purpose of this study was to identify current practices and perceptions around trace element feeding for dairy cows through a Canadian dairy nutritionist survey. An online survey with 23 questions was used to collect data from Canadian dairy nutritionists with the help of professional associations and social media. The survey was active from November 2021 to April 2022.

Dairy cow hoof impact and slide measurements for common Ontario dairy farm floorings.

In the context of understanding lameness and injury from slipping, our objective was to characterize hoof impact and slide of 5 cows walking on 6 flooring surfaces commonly used in Ontario dairy farms: diamond-grooved concrete (DC), sanded epoxy-covered concrete (EC), grooved rubber mat (GR), high-profile rubber mat (HR), low-profile rubber mat (LR), and turf grass (TG; Kentucky bluegrass/fescue mix). Surface hardness was measured on each surface using a Clegg Impact Soil Tester. Five trained lactating Holstein cows were each walked over all 6 surfaces sequentially in a randomized order.

Detection of high-grade cervical neoplasia using extended genotyping: Performance data from the longitudinal phase of the Onclarity trial.

Objectives: The Onclarity cervical cancer screening trial was designed to establish the clinical validity of the Onclarity HPV assay for extended genotyping (xGT) during detection of high-grade cervical neoplasia grades 2 or 3 (≥CIN2 or ≥CIN3). Here, three-year follow up data is presented to evaluate the overall efficacy of these screening strategies, compared to the baseline data.

Methods: At baseline 29,513 women, ≥25 years, had evaluable cytology and valid high-risk HPV results.

Preferences of Dairy Cattle for Supplemental Light-Emitting Diode Lighting in the Resting Area.

Light from the environment is important for vision and regulating various biological processes. Providing supplemental lighting in the stall area could allow for individually targeted or group-level control of light. This study aimed to determine whether dairy cattle had preferences for short-term exposure to white (full-spectrum) light-emitting diode (LED) light or no LED light, yellow-green or white LED light, and blue or white LED light in the stall area.

Dermatofibrosarcoma Protuberans in Children.

Paediatric dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue malignant tumour which displays aggressive local behaviour and has low metastatic potential. The diagnosis is often delayed as DFSP is usually mistaken for other skin conditions, particularly in the early stages of disease. DFSP tends to follow an indolent course after the initial presentation with what is often described as a "rubbery lump".

Liposarcoma subtype recurrence and survival: A UK regional cohort study.

Background: Clinical outcome data in the United Kingdom, Europe, and the United States have yet to facilitate appropriately specific surveillance for liposarcoma histological subtypes, despite being one of the most common soft tissue sarcomas. Therefore, this study aims to demonstrate histologic-specific differences in liposarcoma recurrence, disease progression, and survival and discuss the implications.

Methods And Findings: This cohort study involves patients from a regional sarcoma service in the UK who have had a primary surgical excision of liposarcoma between October 2002 and September 2019.

Development of a novel stall design for dairy cattle: Part II. The effect of minimal stall partitioning on lying behavior, rumination, stall cleanliness, and preference.

Free-stalls for dairy cows promote cleanliness, provide cows with a defined space to lie down, and decrease labor and bedding required for maintenance. However, current stall features can restrict behavior and reduce stall use. The objective of this study was to assess the short-term effect of a novel free-stall design (flexible single-bar partition, no neck rail, increased slope) on stall cleanliness and the lying behavior, rumination, milk production, and preferences of dairy cows in comparison to standard free-stalls (metal loop partitions, neck rail).

Clinical Utility of Reflex Testing with Cancer Biomarkers to Improve Diagnostic Accuracy of Primary Human Papillomavirus Screening.

Background: Human papillomavirus (HPV) testing is the cornerstone of cervical cancer screening, with outstanding sensitivity but only moderate specificity. We evaluated whether reflex testing for cancer biomarkers improves the sensitivity/specificity balance of screening.

Methods: Cervical samples from women in Cape Town, South Africa, ages 30-65 years, were collected and tested with Xpert HPV and with real-time PCR to detect mRNA for cyclin-dependent kinase inhibitor 2A (CDKN2A), topoisomerase 2 alpha (TOP2A), and Ki67 (MKi67).

Development of a novel stall design for dairy cattle: Part I. The effect of an increased slope on lying behavior, rumination, cleanliness, and preference.

The longitudinal slope of a stall is important for positioning cows in the stall and maintaining cleanliness of the stall surface. The objectives of this study were to determine the short-term effect of increasing free-stall slope from 4.5% to 9.

Clinical validation of p16/Ki-67 dual-stained cytology triage of HPV-positive women: Results from the IMPACT trial.

Triage strategies are needed for primary human papillomavirus (HPV)-based cervical cancer screening to identify women requiring colposcopy/biopsy. We assessed the performance of p16/Ki-67 dual-stained (DS) immunocytochemistry to triage HPV-positive women and compared it to cytology, with or without HPV16/18 genotyping. A prospective observational screening study enrolled 35 263 women aged 25 to 65 years at 32 U.

Abiraterone Is Superior to Enzalutamide in Response to Ionizing Radiation.

Abiraterone acetate and Enzalutamide are novel anti-androgens that are key treatments to improve both progression-free survival and overall survival in patients with metastatic castration-resistant prostate cancer. In this study, we aimed to determine whether combinations of AR inhibitors with radiation are additive or synergistic, and investigated the underlying mechanisms governing this. This study also aimed to compare and investigate a biological rationale for the selection of Abiraterone versus Enzalutamide in combination with radiotherapy as currently selection is based on consideration of side effect profiles and clinical experience.

The CERTAIN Study Results: Adjunctive p16 Immunohistochemistry Use in Cervical Biopsies According to LAST Criteria.

The Lower Anogenital Squamous Terminology (LAST) Project recommends the use of p16 immunohistochemistry as an adjunct to morphologic assessment of cervical biopsies according to a specific set of criteria. We analyzed the effect of adjunctive p16 according to LAST criteria in a US-based diagnostic utility study involving 70 surgical pathologists providing a total of 38,500 reads on cervical biopsies. Compared with the results obtained using hematoxylin and eosin-stained slides only, including p16-stained slides per LAST criteria increased sensitivity and specificity for diagnosing histologic high-grade squamous intraepithelial lesions across all cases by 8.

Orthoplastic management of open tibial fractures in children : a consecutive five-year series from a paediatric major trauma centre.

Aims: Open tibial fractures are limb-threatening injuries. While limb loss is rare in children, deep infection and nonunion rates of up to 15% and 8% are reported, respectively. We manage these injuries in a similar manner to those in adults, with a combined orthoplastic approach, often involving the use of vascularised free flaps.

The IMproving Primary Screening And Colposcopy Triage trial: human papillomavirus, cervical cytology, and histopathologic results from the baseline and 1-year follow-up phase.

Background: An increase in human papillomavirus test volumes is expected in the near future because human papillomavirus-based screening protocols are expected to become more widely adopted.

Objective: The IMproving Primary Screening And Colposcopy Triage trial, a prospective, multicenter, US-based cervical cancer screening trial, was conducted to obtain US Food and Drug Administration approvals for the new, high-throughput cobas human papillomavirus (cobas HPV) test for use on the cobas 6800/8800 Systems (cobas HPV) for detecting cervical precancerous and cancerous cells (cervical intraepithelial neoplasia of grade 2 or worse and grade 3 or worse). Here, the baseline demographics, human papillomavirus test results, cervical cytology, and histopathologic results are presented.

Performance of Xpert HPV on Self-collected Vaginal Samples for Cervical Cancer Screening Among Women in South Africa.

Objectives: Self-sampling may increase access to cervical cancer screening in low-resource settings. Using Xpert HPV, we compared test performance of self- and clinician-collected samples in HIV-positive and HIV-negative women in South Africa.

Materials And Methods: Three hundred thirty HIV-positive and 375 HIV-negative women in the screening group and 202 HIV-negative and 200 HIV-positive women in the referral group, aged 30-65 years, participated in the study.

Anxiety and somatization: prevalence and correlates of mental health in older people (60+ years) in Botswana.

Objective: This study explored key factors that influence mental health in older people in Botswana. The prevalence of anxiety and somatization in the elderly population was also calculated.

Methods: A cross-sectional study stratified by district was done to collect information on the elderly ( = 378; age:  = 71.

Analysis of Ugandan cervical carcinomas identifies human papillomavirus clade-specific epigenome and transcriptome landscapes.

Cervical cancer is the most common cancer affecting sub-Saharan African women and is prevalent among HIV-positive (HIV) individuals. No comprehensive profiling of cancer genomes, transcriptomes or epigenomes has been performed in this population thus far. We characterized 118 tumors from Ugandan patients, of whom 72 were HIV, and performed extended mutation analysis on an additional 89 tumors.

Selecting human papillomavirus genotypes to optimize the performance of screening tests among South African women.

Human papillomavirus (HPV) testing is highly sensitive compared to cytology, with the trade-off of being less specific. We investigated whether select combinations of HPV genotypes, ascertained by Linear Array (LA) and Xpert HPV (GX), can optimize sensitivity/specificity trade-offs to detect high-grade cervical intraepithelial neoplasia (CIN2+). In a study in Cape Town, South Africa, 586 women living without and 535 living with HIV, aged 30-65 years, were recruited.

The medial sural artery perforator (MSAP) flap: A versatile flap for lower extremity reconstruction.

Background: The medial sural artery perforator (MSAP) flap provides a thin, pliable and durable soft tissue reconstruction with adequate pedicle length and low donor morbidity. It is an ideal choice for small-to-moderate defects of the lower extremity, although it does have limitations. We report our experience of the flap in a three-pronged anatomical, clinical and patient reported outcome-based study.