Caveolin-1 knockout mitigates breast cancer metastasis to the lungs via integrin α3 dysregulation in 4T1-induced syngeneic breast cancer model.

Caveolin-1 (Cav-1) is a critical lipid raft protein playing dual roles as both a tumor suppressor and promoter. While its role in tumorigenesis, progression, and metastasis has been recognized, the explicit contribution of Cav-1 to the onset of lung metastasis from primary breast malignancies remains unclear. Here, we present the first evidence that Cav-1 knockout in mammary epithelial cells significantly reduces lung metastasis in syngeneic breast cancer mouse models. In vitro, Cav-1 knockout in 4T1 cells suppressed extracellular vesicle secretion, cellular motility, and MMP secretion compared to controls. Complementing this, in vivo analyses demonstrated a marked reduction in lung metastatic foci in mice injected with Cav-1 knockout 4T1 cells as compared to wild-type cells, which was further corroborated by mRNA profiling of the primary tumor. We identified 21 epithelial cell migration genes exhibiting varied expression in tumors derived from Cav-1 knockout and wild-type 4T1 cells. Correlation analysis and immunoblotting further revealed that Cav-1 might regulate metastasis via integrin α3 (ITGα3). In silico protein docking predicted an interaction between Cav-1 and ITGα3, which was confirmed by co-immunoprecipitation. Furthermore, Cav-1 and ITGα3 knockdown corroborated its role in metastasis in the cell migration assay.

Ovarian hyperthecosis in adolescent females: two case reports and a review of the literature.

OBJECTIVES: Ovarian hyperthecosis (OHT) is a rare cause of severe hyperandrogenism in the adolescent age group. We describe two case reports, and present an approach to management in this age group based on a review of the literature. CASE PRESENTATION: Patient A presented at age 13 years with a 2 year history of androphonia and hirsuitism. Her testosterone level was elevated at 8.3 nmol/L, and there was marked enlargement of her ovaries bilaterally. There were no focal adrenal or ovarian lesions identified on imaging. She was treated with a gonadotropin releasing hormone (GnRH) agonist and spironolactone with biochemical and clinical improvement. Patient B presented at age 14 years with secondary amenorrhoea, and a 2 year history of androphonia, hirsutism and androgenetic alopecia. Her testosterone level was 12 nmol/L, and a pelvic ultrasound revealed numerous follicles in each ovary which were otherwise normal in size. She was managed with GnRH agonist initially, and now continues on a combined oral contraceptive pill. CONCLUSIONS: Ovarian hyperthecosis needs to be considered in pre-menopausal women presenting with severe hyperandrogenism, after exclusion of androgen-producing adrenal and ovarian tumours. The principles of management in this age group are gonadotropin suppression and hormone replacement.

Bilateral Oophorectomy Prevalence Among U.S. Women.

Background: Bilateral oophorectomy has been linked to numerous health outcomes, some of which can have a long latency period. Limited data are available on bilateral oophorectomy prevalence among U.S. women. Methods: The National Health Interview Survey fielded measures of bilateral oophorectomy most recently in 2010 and 2015. We pooled these 2 data years to present bilateral oophorectomy prevalence estimates by age-group, race, ethnicity, geographic region, and hysterectomy status. Results: Our study found bilateral oophorectomy was common among older women. Among women aged 70-79 years, 29% reported a bilateral oophorectomy, compared with <1% for women aged 20-29 years. By geographic region, bilateral oophorectomy prevalence among women 20-84 years was 12.3% in the South, 10.8% in the Midwest, 9.4% in the West, and 8.0% in the Northeast. Small numbers limited our ability to generate age-specific estimates for American Indian and Alaska Native women and subgroups of Asian and Hispanic women. Nearly half of women who had a bilateral oophorectomy reported their procedure occurred more than 20 years ago. Among women aged 20-84 years who reported a hysterectomy, 57% reported they also had both of their ovaries removed. Conclusion: Standard measures of incidence rates for ovarian cancer are not adjusted for oophorectomy status. These findings suggest that ovarian cancer incidence rates may be underestimated among older women. Continued monitoring of bilateral oophorectomy prevalence will be needed to track its potential impact on ovarian cancer incidence and numerous other chronic health outcomes.

Participation and psychosocial supports in the school setting for children with type 1 diabetes: A discrete choice experiment of carer priority.

School-based diabetes care is an important consideration for clinicians and families alike. This Discrete-Choice Experiment describes parental preference for enhanced psychosocial and activity-focused supports over academic supports for children with Type 1 diabetes in Australian primary and secondary schools.

Timely Completion of Direct Access Colonoscopy Is Noninferior to Office Scheduled for Screening and Surveillance.

GOALS: We aimed to evaluate whether direct access colonoscopy (DAC) is noninferior to office-scheduled colonoscopy (OSC) for achieving successful colonoscopy. BACKGROUND: DAC may improve access to colonoscopy. We developed an algorithm assessing eligibility, risk for inadequate preparation, and need for nursing/navigator assistance. STUDY: This was a retrospective, single-center study of DAC and OSC patients from June 5, 2018, to July 31, 2019. Patients were 45 to 75 years old with an indication of screening or surveillance. A successful colonoscopy met 3 criteria: complete colonoscopy (cecum, anastomosis, or ileum), adequate preparation (Boston Score ≥2/segment), and performed <90 days from initial patient contact. Unsuccessful colonoscopy did not meet ≥1 criteria. Secondary end points included days to successful colonoscopy, preparation quality, polyp detection, and 10-year recall rate. Noninferiority against risk ratio value of 0.85 was tested using 1-sided alpha of 0.05. RESULTS: A total of 1823 DAC and 828 OSC patients were eligible. DAC patients were younger, with a greater proportion of black patients and screening indications. For the outcome of successful colonoscopy, DAC was noninferior to OSC (DAC vs. OSC: 62.7% vs. 57.1%, RR 1.16, 95% LCL 1.09, P=0.001). For DAC, days to colonoscopy were fewer, and likelihood of 10-year recall after negative screening greater. Boston Score and polyp detection were similar for groups. Black patients were less likely to achieve successful colonoscopy; otherwise, groups were similar. For unsuccessful colonoscopies, proportionally more DAC patients canceled or no-showed while more OSC patients scheduled >90 days. DAC remained noninferior to OSC at 180 days. CONCLUSIONS: DAC was noninferior to OSC for achieving successful colonoscopy, comparing similarly in quality and efficiency outcomes.

Constitutive Innate Immunity and Systemic Responses to Infection of the American Alligator (Alligator mississippiensis).

Uninfected alligators (Alligator mississippiensis) exhibited high constitutive levels of hepatic gene expression related to immune function, whereas the highest-expressed hepatic genes of uninfected mice were related to metabolism. Intraperitoneal challenge of mice with bacterial lipopolysaccharide results in dramatic inflammatory effects including peritoneal ascites, febrile response, dramatic alterations in electrophoretic serum profile, and mortality. In contrast, coelomic injection of alligators with 200× the murine LD50 of intraperitoneal bacterial lipopolysaccharide resulted in no changes in serum protein profiles, behavioral effects, mortality, and no coelomic ascites. However, injection of juvenile alligators with live bacteria resulted in a titer-dependent decrease in metabolic rate, as measured by oxygen consumption. These results are the opposite of those observed for mammalian and avian species. The decreased oxygen consumption was not accompanied by changes in heart or respiration rate, indicating that this phenomenon was not due to bradycardia or bradypnea. Interestingly, challenge of alligators with bacteria resulted in the complete expulsion of digestive tract contents within four hours. We interpret these activities as temporary minimization of other biological systemic activities to redirect and devote energy to immune function. The reallocation of resources within an organism to fight infection without increases in metabolic rate has not been described in other animals.

Disseminated Aspergillus citrinoterreus and concurrent localized dermal phaeohyphomycosis in an immunosuppressed dog.

Key Clinical message: We report on a dog with immune-mediated hemolytic anemia (IMHA) treated with immunomodulatory therapy that developed phaeohyphomycosis and Aspergillus citrinoterreus infections. This is the first reported case of A. citrinoterreus in dogs. It details cytological and microbiological findings leading to diagnosis and highlights the importance of investigating new lesions in immunocompromised patients. Abstract: A 5-year-old Staffordshire terrier mix treated with immunosuppressive therapy for IMHA was diagnosed with concurrent disseminated A. citrinoterreus and localized Curvularia lunata infections. This case highlights the potential development of multiple concurrent opportunistic fungal infections and is the first reported case of A. citrinoterreus infection in a dog.

Recent advances in phase change materials for thermal energy storage.

Efficient storage of thermal energy can be greatly enhanced by the use of phase change materials (PCMs). The selection or development of a useful PCM requires careful consideration of many physical and chemical properties. In this review of our recent studies of PCMs, we show that linking the molecular structures of organic molecules to their physical properties can be used to focus attention on the most useful PCMs, including eutectic mixtures. Two of the major limitations concerning broader use of phase change materials are low thermal conductivity, especially for organic phase change materials, and suitable containment. We have addressed both issues in our recent investigations of novel form-stable composite PCMs with a freeze-cast matrix. The use of thorough experimental investigations, including cycling of materials hundreds or thousands of times through the melt-freeze processes, promotes our goals of advancing the use of PCMs for increased energy efficiency and sustainability.

Paediatric diabetes-related presentations to emergency departments in Victoria, Australia from 2008 to 2018.

OBJECTIVES: Despite significant treatment advances in paediatric diabetes management, ED presentations for potentially preventable (PP) complications such as diabetic ketoacidosis (DKA) remains a major issue. We aimed to examine the characteristics, rates and trends of diabetes-related ED presentations and subsequent admissions in youth aged 0-19 years from 2008 to 2018. METHODS: Data were obtained from the Victorian Emergency Minimum Dataset and the National Diabetes Register. A diabetes-related ED presentation is defined using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification diagnosis codes. 'Non-preventable' presentations were the number of youths with newly diagnosed diabetes, and the remaining are classified as PP diabetes-related presentations. Poisson regression model was used to examine the trends in incidence rate and prevalence. RESULTS: Four thousand eight hundred and seventy-two (59%) of 8220 presentations were PP, 4683 (57%) were for DKA whereas 6200 (82%) required hospital admission. Diabetes-related ED presentations decreased from 38.4 to 27.5 per 100 youth with diabetes per year between 2008 and 2018 (ß = -0.04; confidence interval [CI] -0.04 to -0.03; P < 0.001). Females, those aged 0-4 years and rural youth had higher rates of ED presentations than males, older age groups and metropolitan youth. DKA presentations decreased from 20.1 presentations per 100 youth with diabetes in 2008-2009 to 14.9 presentations per 100 youth with diabetes in 2017-2018. The rate of DKA presentations was 68% higher in rural areas compared to metropolitan areas (incidence rate ratio 1.68; CI 1.59-1.78; P < 0.001). CONCLUSIONS: Although the rates of diabetes-related ED presentations declined, PP diabetes-related presentations and subsequent hospitalisation remain high. Patient level research is required to understand the increased DKA presentations in rural youth.

Have interventions aimed at assisting general practitioners in facilitating earlier diagnosis of type 1 diabetes in children been successful? A systematic review protocol.

BACKGROUND: Early diagnosis of type 1 diabetes in children is critical to prevent deterioration to diabetic ketoacidosis (DKA), a state where the body's insulin levels are critically low resulting in the use of fat for fuel and the accumulation of ketones. DKA is a life-threatening emergency where dehydration and cerebral oedema can quickly develop and lead to death. Despite treatment, DKA also has harmful impacts on cognition and brain development. Most children admitted to a hospital with DKA see their general practitioner in the week leading up to their admission. A delay in referral from general practice can result in delays in commencing lifesaving insulin therapy. Prior systematic reviews have explored publicity campaign interventions aimed at recognising type 1 diabetes earlier; however, no reviews have explored these interventions targeted at reducing the delay after presentation to the general practitioner. This systematic review aims to summarise interventions that target the diagnostic delay emerging from general practice and to evaluate their effectiveness in reducing DKA admissions. METHODS: Six databases (Ovid (MEDLINE), Web of Science, EMBASE, CINAHL, Evidence-Based Medicine Reviews (EBMR) and Google Scholar) will be searched to identify studies exploring interventions to reduce diagnostic delay in children with type 1 diabetes, and hence DKA, in general practice. The primary outcome will be the number of DKA admissions to a hospital following a delay in general practice. The secondary outcome will be the behaviour of general practitioners with respect to urgent referral of children with type 1 diabetes. Title, abstract and full-text screening for exclusion and inclusion of publications will be completed by two independent reviewers. Any risks of bias within individual studies will be assessed by two independent reviewers, using the Risk Of Bias In Non-Randomized Studies of Interventions tool. Our confidence in the overall body of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation. ETHICS AND DISSEMINATION: The systematic review will be disseminated via publication and potentially in conference presentations. Ethics is not required for a systematic review of secondary data. PROSPERO REGISTRATION NUMBER: CRD42023412504.

Understanding the hospital discharge planning process for medical patients with dementia.

Background: Poor hospital discharge processes can result in the readmission of patients and potentially increase the stress levels of carers. Therefore, this study sought to understand the factors related to the discharge planning process for patients with dementia.Methods: The researchers interviewed 32 carers of patients with dementia and 20 hospital staff who worked on medical wards in a United Kingdom (UK) hospital. The semi-structured interviews were analysed thematically using a systems theory (patient-carer-staff relationships, hospital equipment and policies).Results: The findings indicated that the following factors could either have a positive or negative impact on discharge planning: patient (e.g. cognitive capacity), carer (e.g. preconceived ideas about care homes), staff (e.g. communication skills), policy (e.g. procedures such as discharge meetings), equipment (e.g. type of service provider delivering the equipment) and the wider social context (e.g. availability of specialist dementia beds in care homes).Conclusion: It is important for hospital staff to adopt a systems perspective and to integrate the different elements of the hospital system when planning for patients' discharge.

Up-to-Date Breast, Cervical, and Colorectal Cancer Screening Test Use in the United States, 2021.

INTRODUCTION: We examined national estimates of breast, cervical, and colorectal cancer (CRC) screening test use and compared them with Healthy People 2030 national targets. Test use in 2021 was compared with prepandemic estimates. METHODS: In 2022, we used 2021 National Health Interview Survey (NHIS) data to estimate proportions of adults up to date with US Preventive Services Task Force recommendations for breast (women aged 50-74 y), cervical (women aged 21-65 y), and CRC screening (adults aged 50-75 y) across sociodemographic and health care access variables. We compared age-standardized estimates from the 2021 and 2019 NHIS. RESULTS: Percentages of adults up to date in 2021 were 75.7% (95% CI, 74.4%-76.9%), 75.2% (95% CI, 73.9%-76.4%), and 72.2% (95% CI, 71.2%-73.2%) for breast, cervical, and CRC screening, respectively. Estimates were below 50% among those without a wellness check in 3 years (all screening types), among those without a usual source of care or insurance (aged <65 y) (breast and CRC screening), and among those residing in the US for less than 10 years (CRC screening). Percentages of adults who were up to date with breast and cervical cancer screening and colonoscopy were similar in 2019 and 2021. Fecal occult blood/fecal immunochemical test (FOBT/FIT) use was modestly higher in 2021 (P < .001). CONCLUSIONS: In 2021, approximately 1 in 4 adults of screening age were not up to date with breast, cervical, and CRC screening recommendations, and Healthy People 2030 national targets were not met. Disparities existed across several characteristics, particularly those related to health care access. Breast, cervical, and colonoscopy test use within recommended screening intervals approximated prepandemic levels. FOBT/FIT estimates were modestly higher in 2021.

Variation in hysterectomy prevalence and trends among U.S. States and Territories-Behavioral Risk Factor Surveillance System, 2012-2020.

PURPOSE: We estimated up-to-date state- and territory-level hysterectomy prevalence and trends, which can help correct the population at risk denominator and calculate more accurate uterine and cervical cancer rates. METHODS: We analyzed self-reported data for a population-based sample of 1,267,013 U.S. women aged ≥ 18 years who participated in the Behavioral Risk Factor Surveillance System surveys from 2012 to 2020. Estimates were age-standardized and stratified by sociodemographic characteristics and geography. Trends were assessed by testing for any differences in hysterectomy prevalence across years. RESULTS: Hysterectomy prevalence was highest among women aged 70-79 years (46.7%) and ≥ 80 years (48.8%). Prevalence was also higher among women who were non-Hispanic (NH) Black (21.3%), NH American Indian and Alaska Native (21.1%), and from the South (21.1%). Hysterectomy prevalence declined by 1.9 percentage points from 18.9% in 2012 to 17.0% in 2020. CONCLUSIONS: Approximately one in five U.S. women overall and half of U.S. women aged ≥ 70 years reported undergoing a hysterectomy. Our findings reveal large variations in hysterectomy prevalence within and between each of the four census regions and by race and other sociodemographic characteristics, underscoring the importance of adjusting epidemiologic measures of uterine and cervical cancers for hysterectomy status.

Twenty years of collaborative research to enhance community practice for cancer prevention and control.

The Cancer Prevention and Control Research Network (CPCRN) was established in 2002 to conduct applied research and undertake related activities to translate evidence into practice, with a special focus on the unmet needs of populations at higher risk of getting cancer and dying from it. A network of academic, public health and community partners, CPCRN is a thematic research network of the Prevention Research Centers Program at the Centers for Disease Control and Prevention (CDC). The National Cancer Institute's Division of Cancer Control and Population Sciences (DCCPS) has been a consistent collaborator. The CPCRN has fostered research on geographically dispersed populations through cross-institution partnerships across the network. Since its inception, the CPCRN has applied rigorous scientific methods to fill knowledge gaps in the application and implementation of evidence-based interventions, and it has developed a generation of leading investigators in the dissemination and implementation of effective public health practices. This article reflects on how CPCRN addressed national priorities, contributed to CDC's programs, emphasized health equity and impacted science over the past twenty years and potential future directions.

A narrative review of staff views about dementia care in hospital through the lens of a systems framework.

Background: Significant numbers of people with dementia are admitted into acute settings. They are likely to face poor health outcomes during hospitalisation. There is the need to fully understand the care provided to people with dementia through novel methods such as a systems approach (i.e. human interactions, policy, environment and equipment). Aim: The aim of this literature review is to explore hospital practitioners' views on dementia care and to analyse findings using a systems approach. Methods: We conducted a narrative review of primary studies that examined dementia care in acute settings. We analysed a total of 33 papers using Thomas and Harden's thematic synthesis guidelines. Results: Thirty-three papers met the inclusion criteria for the review. The findings were as follows: (1) staff-patient relationships (e.g. coping with difficult behaviour), (2) staff-family relationships (e.g. the benefits of involving families in patient care), (3) staff-staff relationships (e.g. building a robust multidisciplinary team), (4) staff-patient care decisions (e.g. decisions directly related to the patient), (5) the environment (e.g. difficulty in adjusting to the hospital environment), (6) policies (e.g. hospital bureaucratic processes) and (7) equipment (e.g. pain assessment tools). Conclusion: The paper revealed multidimensional challenges in the provision of dementia care within hospitals. We conclude that training programmes, hospital policies and processes aimed at improving outcomes for patients with dementia should adopt a systems approach which focuses on the relational, environmental, procedural and instrumental aspects of the hospital system.

Exercises With Optimal Scapulothoracic Muscle Activation for Individuals With Paraplegia.

Background: Individuals with paraplegia and coexisting trunk and postural control deficits rely on their upper extremities for function, which increases the risk of shoulder pain. A multifactorial etiology of shoulder pain includes "impingement" of the supraspinatus, infraspinatus, long head of the biceps tendons, and/or subacromial bursa resulting from anatomic abnormalities, intratendinous degeneration, and altered scapulothoracic kinematics and muscle activation. Targeting serratus anterior (SA) and lower trapezius (LT) activation during exercise, as part of a comprehensive plan, minimizes impingement risk by maintaining optimal shoulder alignment and kinematics during functional activities. To prevent excessive scapular upward translation, minimizing upper trapezius (UT) to SA and LT activation is also important. Objectives: To determine which exercises (1) maximally activate SA and minimize UT:SA ratio and (2) maximally activate LT and minimize UT:LT ratio. Methods: Kinematic and muscle activation data were captured from 10 individuals with paraplegia during four exercises: "T," scaption (sitting), dynamic hug, and SA punch (supine). Means and ratios were normalized by percent maximum voluntary isometric contraction (MVIC) for each muscle. One-way repeated measures analysis of variance determined significant differences in muscle activation between exercises. Results: Exercises were rank ordered: (1) maximum SA activation: SA punch, scaption, dynamic hug, "T"; (2) maximum LT activation: "T," scaption, dynamic hug, SA punch; 3) minimum UT:SA ratio: SA punch, dynamic hug, scaption, "T"; and (4) minimum UT:LT ratio: SA punch, dynamic hug, "T," scaption. Exercise elicited statistically significant changes in percent MVIC and ratios. Post hoc analyses revealed multiple significant differences between exercises (p < .05). Conclusion: SA punch produced the greatest SA activation and lowest ratios. Dynamic hug also produced optimal ratios, suggesting supine exercises minimize UT activation more effectively. To isolate SA activation, individuals with impaired trunk control may want to initiate strengthening exercises in supine. Participants maximally activated the LT, but they were not able to minimize UT while upright.

Evaluation of serum 25-hydroxyvitamin D, C-reactive protein, and haptoglobin as biomarkers in dogs newly diagnosed with histoplasmosis.

BACKGROUND: Serum 25-hydroxyvitamin (OH)D, C-reactive protein (CRP), and haptoglobin are useful biomarkers in various infectious diseases and inflammatory disorders in dogs, but their utility in histoplasmosis is unknown. OBJECTIVE: Determine if serum 25(OH)D, CRP, and haptoglobin concentrations are different in dogs with histoplasmosis compared to healthy controls and whether serum globulin, albumin, CRP, or haptoglobin are associated with 25(OH)D concentration. ANIMALS: Twenty-two client-owned dogs (histoplasmosis, n = 12; controls, n = 10). METHODS: Prospective case-control study. Dogs with histoplasmosis were categorized as pulmonary, disseminated, or gastrointestinal (GI) tract. Serum 25(OH)D was measured using modified high-performance liquid chromatography (HPLC). Serum CRP and haptoglobin were measured with ELISA assays. RESULTS: Dogs with histoplasmosis were grouped as disseminated (n = 8) and GI tract (n = 4). No dogs had pulmonary tract involvement alone. Dogs with histoplasmosis (median, interquartile range [IQR]; 11.6 ng/mL, 16.8) had lower serum 25(OH)D concentrations than controls (35.7 ng/mL, 17.6; P < .001). Serum CRP and haptoglobin concentrations were higher in dogs with histoplasmosis (CRP: median, IQR; 63.5 mg/L, 37.1 and haptoglobin: 459.7 mg/dL, 419.6) than controls (CRP: 1.9 mg/L, 2; P < .001 and haptoglobin: 85.5 mg/dL, 106.7; P = .003). Serum 25(OH)D concentration was positively associated with fold change in serum albumin concentration (ρ = 0.77; P < .001), and negatively associated with fold change in serum globulin (ρ = -0.61; P = .003) and CRP concentrations (ρ = -0.56; P = .01). CONCLUSION AND CLINICAL IMPORTANCE: Assay of serum 25(OH)D, CRP, and haptoglobin could have clinical value in dogs with histoplasmosis.

A 46-Year-Old Woman With Chronic Dyspnea and Diarrhea.

CASE PRESENTATION: A 46-year-old previously healthy woman presented with dyspnea, fatigue, and diarrhea. She had been experiencing these symptoms for > 1 year, but they had worsened in the few weeks prior to presentation. She had become progressively dyspneic on exertion and at rest and had increased the number of pillows she was sleeping on at night. She reported having episodes of nonbloody, watery diarrhea five to six times a day. The episodes were not associated with abdominal pain or recent travel and occurred even with fasting. Review of systems was positive for intermittent hot flashes, heart palpitations, and myalgias. She was premenopausal. She denied fever, weight loss, cough, hemoptysis, chest pain, or new edema. She had a pertinent medical history of gastritis, a nonspecific murmur since childhood, current tobacco use with a five pack-year history, and a family history of non-first-degree relatives having lung, breast, and colon cancer. She had not received medical care since moving from Brazil to the United States 4 years earlier.