Diet and Metabolism in CKD-Related Metabolic Acidosis.

Metabolic acidosis is a common complication in patients with chronic kidney disease that occurs when the daily nonvolatile acid load produced in metabolism cannot be excreted fully by the kidney. A reduction in urine net acid excretion coupled with a high nonvolatile acid load may play a role in its pathogenesis. Diet is important in generation of the nonvolatile acid load. Acids are produced from metabolism of dietary protein and from the endogenous production of organic anions from neutral precursors. Acids can be balanced by alkali precursors ingested in the diet in the form of combustible organic anions. These typically are reflected indirectly by the excess of mineral cations to mineral anions in a food or diet. These principles underscore widely used methods to estimate the nonvolatile acid load from dietary intake using formulas such as the net endogenous acid production equation and the potential renal acid load equation. Empiric data largely validate these paradigms with high net endogenous acid production and potential renal acid load contributed by foods such as protein, grains, and dairy, and low net endogenous acid production and potential renal acid load contributed by fruits and vegetables along with corresponding dietary patterns. Although further studies are needed to understand the health benefits of altering nonvolatile acid load via diet, this review provides a detailed assessment on our current understanding of the role of diet in chronic kidney disease-related acidosis, providing an updated resource for researchers and clinicians.

Pathways to improve nephrologist comfort in managing patients on in-center or home self-care dialysis.

In end-stage kidney disease (ESKD), patient engagement and empowerment are associated with improved survival and complications. However, patients lack education and confidence to participate in self-care. The development of in center self-care hemodialysis can enable motivated patients to allocate autonomy, increase satisfaction and engagement, reduce human resource intensiveness, and cultivate a curiosity about home dialysis. In this review, we emphasize the role of education to overcome barriers to home dialysis, strategies of improving home dialysis utilization in the COVID 19 era, the significance of in-center self-care dialysis (e.g., cost containment and empowering patients), and implementation of an in-center self-care dialysis as a bridge to home hemodialysis (HHD).

Importance of Metabolic Acidosis as a Health Risk in Chronic Kidney Disease.

Human kidneys are well adapted to excrete the daily acid load from diet and metabolism in order to maintain homeostasis. In approximately 30% of patients with more advanced stages of CKD, these homeostatic processes are no longer adequate, resulting in metabolic acidosis. Potential deleterious effects of chronic metabolic acidosis in CKD, including muscle wasting, bone demineralization, hyperkalemia, and more rapid progression of CKD, have been well cataloged. Based primarily upon concerns related to nutrition and bone disease, early Kidney Disease Outcomes Quality Initiative guidelines recommended treating metabolic acidosis with alkali therapy targeting a serum bicarbonate ≥22 mEq/L. More recent guidelines have suggested similar targets based upon potential slowing of CKD progression. However, appropriately powered, long-term, randomized controlled trials to study efficacy and safety of alkali therapy for these outcomes are largely lacking. As a result, practice among physicians varies, underscoring the complexity of treatment of chronic metabolic acidosis in real-world CKD practice. Novel treatment approaches and rigorous phase 3 trials may resolve some of this controversy in the coming years. Metabolic acidosis is an important complication of CKD, and where it "falls" in the priority schema of CKD care will depend upon the generation of strong clinical evidence.

Voicing Beliefs on Global Leadership for Dentistry.

BACKGROUND: Dental leadership in different models of care is not well documented, and therefore the objectives of this study were to explore how dental leaders develop their own leadership and how they engage others to increase access to oral health services as well as to describe perceived challenges in developing coalitions for promoting oral health care. METHODS: We adopted a qualitative descriptive research methodology. We recruited dental leaders using a purposeful sampling approach and a snowball technique. Data were collected using a remote digital platform; we organised semi-structured interviews based on the LEADS conceptual framework. Saturation was reached after 11 interviews. Data analysis included the following iterative steps: decontextualisation, recontextualisation, categorisation, and data compilation. The analysis was performed manually, assisted by the use of QDA Miner software. RESULTS: Fourteen dental leaders participated in the study. Our analysis revealed 3 overarching themes: (I) lead self, with 3 subthemes: leadership insights; leadership traits; opportunity-role model dyad; (II) leadership strategies; and (III) challenges in leadership development, with 3 subthemes: limited engaged practice and workforce, valorise the image of dentistry, and lack of leadership training. CONCLUSIONS: Our research findings showed that, despite a limited scope of leadership in dentistry, the dental leaders recognise its importance and acknowledge the need for formal training and mentorship at different levels. This study identified challenges in dental leadership development that could further orient dental education programmes and support the implementation of evidence-based, high-quality, and efficient oral health services.

CXCR6-CXCL16 Axis Promotes Breast Cancer by Inducing Oncogenic Signaling.

Precise mechanisms underlying breast cancer (BrCa) metastasis are undefined, which becomes a challenge for effective treatments. Chemokine signaling instigates the trafficking of cancer cells in addition to leukocytes. This study aimed to ascertain the clinical and biological significance of the CXCR6/CXCL16 signaling axis in the pathobiology of BrCa. Our data show a higher expression of CXCR6 in BrCa cell lines and tissues. Stage-III BrCa tissues express significantly higher CXCR6 compared to stage-II tissues. The ligand, CXCL16, could remain tethered to the cell surface, and, after proteolytic shedding of the ectodomain, the N-terminal fragment is released, converting it to its oncogenic, soluble form. Like CXCR6, N-terminal CXCL16 and ADAM-10 were significantly higher in stage-III than stage-II, but no significant difference was observed in the C-terminal fragment of CXCL16. Further, stimulation of the CXCR6/CXCL16 axis activated Src, FAK, ERK1/2, and PI3K signaling pathways, as per antibody microarray analysis, which also underlie CXCL16-induced F-actin polymerization. The CXCR6/CXCL16 axis induces cytoskeleton rearrangement facilitating migration and invasion and supports BrCa cell survival by activating the PI3K/Akt pathway. This study highlights the significance of the CXCR6/CXCL16 axis and ADAM10 as potential therapeutic targets for advanced-stage BrCa.

Concomitant Medication Usage with Levodopa-Carbidopa Intestinal Gel: Results from the COSMOS Study.

BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) is administered directly to the small intestine of patients with advanced Parkinson's disease (APD) to help maintain stable plasma levodopa levels. OBJECTIVE: The objective of this study was to investigate the effect of LCIG in reducing polypharmacy for the treatment of APD. METHODS: The COmedication Study assessing Mono- and cOmbination therapy with levodopa-carbidopa inteStinal gel (COSMOS) is a large, real-world, multinational observational study investigating comedication use with LCIG. All enrolled patients had used LCIG for ≥12 months and data were collected cross-sectionally (study visit) and retrospectively. The primary endpoint was the percentage of patients using LCIG as monotherapy (without add-on PD medications) at initiation and at 3, 6, 9, and 12 months thereafter. RESULTS: Overall, 409 patients were enrolled from 14 countries and were treated with LCIG for a mean of 35.8 ± 23.2 months. A total of 15.2% of patients initiated LCIG as monotherapy and 31.7% were receiving monotherapy at 12 months after initiation. The mean duration of LCIG monotherapy was 39.3 ± 25.6 months. Use of add-on medications decreased over time with all LCIG regimens. From LCIG initiation to the patient visit, mean off time decreased by 3.8, 4.6, and 3.9 hours/day for LCIG monotherapy, LCIG daytime monotherapy, and LCIG polytherapy groups, respectively, while duration of dyskinesia decreased by 1.7, 2.0, and 1.9 hours/day, respectively. Adverse events likely related to study treatment occurred in 112 patients (27.4%) during LCIG treatment. CONCLUSIONS: LCIG is an effective long-term monotherapy option with a positive risk-benefit profile and contributes to reduced polypharmacy for patients with APD. © 2021 The AbbVie Inc. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Development and evaluation of an augmented reality education program for pediatric research.

BACKGROUND: Children often have limited understanding of clinical research and what they might expect from participating in a clinical study. Studies, however, suggest that multimedia delivery of medical and research information may promote greater understanding and engagement compared with standard written approaches. AIM: This study was designed to examine the effects of a novel interactive augmented reality (AR) program on children's understanding of clinical research. METHODS: Children (ages 7-13 years) were randomized to receive the basic information about clinical research using either a printed storybook (control) or the same storybook enhanced using a video see-through AR iPad program (AR) with embedded interactive quizzes. Children were interviewed to assess their understanding of the material before (pre-test) and after (post-test) receiving either of the randomized interventions. Both parents and children completed short surveys to measure their perceptions of the information delivery. RESULTS: Ninety-one parent/child dyads were included in the analysis. There were no differences between the control and AR children's pre-test understanding of the research information. However, both groups demonstrated significant and similar improvements in post-test understanding. Parents of children in the AR group found the information to be of higher quality and greater clarity compared with the control group, and 91.7% of children in the AR group found the inclusion of interactive quizzes to be helpful. Both parents and children found the AR program very easy to use and 85.0 % and 71.2%, respectively, indicated that if recruited for a future study that they would prefer information delivered using some type of iPad AR program together with a discussion with the researcher. CONCLUSIONS: Results demonstrated the importance of providing children and parents with information in an easy to read and visually compelling manner. Although both groups demonstrated improved understanding, children and their parents preferred the AR program and reported a preference for receiving information using computer-based technology. Given the seemingly insurmountable challenge of keeping children and families engaged in health research related information exchange, the use of AR would appear to provide a novel and effective vehicle for enhancing children's and parents assimilation and understanding of research (and medical) information and as a potential tool to optimize the informed consent and assent processes. RELEVANCE FOR PATIENTS: This study reinforces the importance in providing information to research participants and patients in an easy-to-read and visually salient manner. Although the AR program used in this study did not result in an increased level of understanding, AR was deemed the preferred method of information delivery. It is hoped that the results of this study will serve as a platform for future studies.

Creating a centralized social media recruitment service for research teams at the University of Michigan.

Successful social media recruitment requires specific expertise and constant upkeep, placing an inordinate burden on study teams. Over half of the study teams at the University of Michigan (U-M) surveyed about recruitment assistance needs indicated that they wanted to use social media as a recruitment strategy, but lacked the expertise to do so. We thus built a service to centralize social media recruitment across the university. This involved assembling the right expertise, creating a centralized social media profile, creating linkages to other digital recruitment platforms, building the financial structure, and operationalizing the service. So far, we have helped 94 study teams launch social media campaigns on Facebook and Instagram. These campaigns resulted in 1,653,675 users being reached, of which 20,546 users actively showed interest in participating in the corresponding studies. We followed 18 studies further, who reported a total of 345 social media participants as being enrolled, resulting in an average cost-per-contact (CPC) of $8.72 and an average cost-per-enrollee (CPE) of $55.21. The combination of communication expertise, streamlined administrative processes, and linkages to a centralized research participation registry has allowed us to help a large number of study teams seamlessly engage broad and diverse populations.

Germline Genetic Testing: What the Breast Surgeon Needs to Know.

PURPOSE: The American Society of Breast Surgeons (ASBrS) sought to provide educational guidelines for breast surgeons on how to incorporate genetic information and genomics into their practice. METHODS: A comprehensive nonsystematic review was performed of selected peer-reviewed literature. The Genetics Working Group of the ASBrS convened to develop guideline recommendations. RESULTS: Clinical and educational guidelines were prepared to outline the essential knowledge for breast surgeons to perform germline genetic testing and to incorporate the findings into their practice, which have been approved by the ASBrS Board of Directors. RECOMMENDATIONS: Thousands of women in the USA would potentially benefit from genetic testing for BRCA1, BRCA2, and other breast cancer genes that markedly increase their risk of developing breast cancer. As genetic testing is now becoming more widely available, women should be made aware of these tests and consider testing. Breast surgeons are well positioned to help facilitate this process. The areas where surgeons need to be knowledgeable include: (1) identification of patients for initial breast cancer-related genetic testing, (2) identification of patients who tested negative in the past but now need updated testing, (3) initial cancer genetic testing, (4) retesting of patients who need their genetic testing updated, (5) cancer genetic test interpretation, posttest counseling and management, (6) management of variants of uncertain significance, (7) cascade genetic testing, (8) interpretation of genetic tests other than clinical cancer panels and the counseling and management required, and (9) interpretation of somatic genetic tests and the counseling and management required.

Adapting the buying funnel model of consumer behavior to the design of an online health research recruitment tool.

INTRODUCTION: UMHealthResearch is the University of Michigan's digital health research recruitment platform. It allows health researchers to connect efficiently with potentially eligible volunteers. METHODS: In 2013, the UMHealthResearch team strategically adapted a consumer behavior model, the buying funnel, to create the Digital Health Research Participation Funnel. The Digital Health Research Participation Funnel was then used to design a more active way for potential participants to volunteer for research studies through UMHealthResearch. RESULTS: In the 5 years before the redesign (2007-2012), an average of 1844 new accounts were created every year, whereas in the completed years after the redesign (2013-2016) the annual average improved to 3906, an increase of 111%. CONCLUSION: Although a randomized design was not possible in this instance, these preintervention and postintervention data suggest that the focus on user experience is an effective strategy for improving web-based research recruitment platforms.

Taking the plunge: the benefits of aquanatal exercise.

In this article, Anita Johnson carried out an interview with Cathy Charles, a midwife and aquanatal teacher in Wiltshire, to explore the benefits of aquanatal exercise in pregnancy and the postnatal period; this is particularly pertinent at a time when there is a focus on mental wellbeing and rising obesity and caesarean section rates. Anita wanted a first-hand account from a midwife trained in water-based fitness and her experiences of delivering aquanatal classes to pregnant women. Following Anita's own experience of participating in the aquanatal class and Cathy's entertaining interview she hopes it may encourage midwives to promote this form of exercise and to pursue recognized training to deliver their own classes.

Origin of the low frequency radiation emitted by radiative polaritons excited by infrared radiation in planar La2O3 films.

Upon excitation in thin oxide films by infrared radiation, radiative polaritons are formed with complex angular frequency ω, according to the theory of Kliewer and Fuchs (1966 Phys. Rev. 150 573). We show that radiative polaritons leak radiation with frequency ω(i) to the space surrounding the oxide film. The frequency ω(i) is the imaginary part of ω. The effects of the presence of the radiation leaked out at frequency ω(i) are observed experimentally and numerically in the infrared spectra of La(2)O(3) films on silicon upon excitation by infrared radiation of the 0TH type radiative polariton. The frequency ω(i) is found in the microwave to far infrared region, and depends on the oxide film chemistry and thickness. The presented results might aid in the interpretation of fine structures in infrared and, possibly, optical spectra, and suggest the study of other similar potential sources of electromagnetic radiation in different physical scenarios.

Effects of metallic, semiconducting, and insulating substrates on the coupling involving radiative polaritons in thin oxide films.

Through simulations, this work explores the effects of conducting, semiconducting, and insulating substrates on the absorption of infrared radiation by radiative polaritons in oxide layers with thicknesses that range from 30 nm to 9 µm. Using atomic layer deposition, oxide layers can be formed in the nanometer scale. Our results suggest that the chemistry and conductivity of the substrate determine the amount of absorption by radiative polaritons in oxide layers thinner than the skin depth. The effects of the chemistry and conductivity of the substrate are especially effective for oxide films thinner than about 250 nm, which we label as the substrate sensitive thickness of the oxide film.

Young, pregnant and in need of support.

This is an interview with a young parent about her experience of being pregnant at 17. NICE released their guidelines in October 2010 to recommend a flexible model of tailored antenatal care for young parents. Prior to this Bath had set up a Young Parents' One Stop Shop offering antenatal provision in the form of antenatal classes, antenatal appointments at the same location and a range of other services to be accessed at the same time. Anita wanted a first hand account of a young mother's thoughts and feelings during pregnancy and whether they were in line with the recommendations of NICE.

Performance evaluation for diversity programs.

This policy paper addresses the problem of underrepresentation of minorities in the health care professions. Projections are that by 2050 minorities will represent 49% of the U.S. population. Several notable reports suggest that the health care of underrepresented minorities is improved when providers of similar ethnic and racial backgrounds provide the care. However, minority representation in the health care professions has not kept pace with the increase of minorities in the population. A variety of groups (federal, state, private, and health professional educational institutions) have provided billions of dollars toward increasing the number of underrepresented minority health care providers. However, the effectiveness of these programs is not readily evident. Therefore, we recommend comprehensive evaluations of programs funded to increase diversity in the health professions and the development of a Minority Health Care Professionals Center to assume accountability for monitoring programs that receive funding to increase the number of underrepresented minority health care providers.

Gut glutathione metabolism and changes with 7,12-DMBA and glutamine.

INTRODUCTION: The mechanism by which oral glutamine (GLN) prevents 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer is unknown. While GLN triples the negative extraction of gut glutathione (GSH) in rats, DMBA significantly disrupts it. Actual gut GSH flux has not been reported. We hypothesized that the gut is a producer of GSH; DMBA blocks gut GSH production and supplemental oral GLN antagonizes this effect. MATERIALS AND METHODS: Eighty Sprague-Dawley rats were randomized to four groups (n = 20/group): DMBA + GLN, DMBA + FA, OIL + GLN, OIL + FA. Rats (age 50 days) were gavaged with a one-time dose of 100 mg/kg DMBA or oil. Rats were gavaged with AES-14 as GLN (1 gm/kg/day) or an isonitrogenous amount of Freamine (FA) from 1 week before till sacrifice at 1 week after DMBA (greatest effect on gut GSH extraction). Arterial and portal blood was taken for GLN and GSH levels, and blood flow was measured using (14)C-PAH. Gut GLN and GSH fluxes (uptake or production) were calculated. RESULTS: DMBA abrogated the normal GSH production (negative flux) in OIL + FA while not affecting GLN metabolism. GLN maintained GSH production in DMBA + GLN. CONCLUSIONS: Oral GLN restores to normal GSH production in DMBA-treated animals suggesting one of the mechanism(s) by which GLN prevents breast cancer in this model. Unchanged uptake of GLN in the DMBA-treated animals may indicate a block in GSH transport rather than actual intracellular production.

Touch preparation of breast core needle specimens is a new method for same-day diagnosis.

BACKGROUND: Touch preparation cytology (TPC) has proven to be a quick and accurate intraoperative diagnostic tool for excisional breast biopsy, margins and sentinel nodes. We hypothesized that TPC of core needle biopsy (CNB) specimens can provide a same-day diagnosis in the outpatient setting. METHODS: Outpatients presenting with breast lesions underwent TPC of biopsy cores performed by biopsy gun or vacuum-assisted CNB. The TPC results were compared with the final diagnosis of CNB specimens. RESULTS: In all, 199 CNB and TP were performed between August 1997 and October 2002. Twenty-nine percent of lesions were malignant. Touch preparation was deferred in 21% of cases. In the remaining 157 evaluable cases, TPC had an accuracy of 89% and a false negative rate of 26%. The sensitivity, specificity, positive predictive value and negative predictive value of TPC were 74%, 97%, 93%, and 86% respectively. CONCLUSIONS: Touch preparation cytology on CNB can be performed simply in the outpatient setting. Collaboration between the surgeon and pathologist allows TP to be an accurate means of same-day pathological determination.

Effect of glutamine on glutathione, IGF-I, and TGF-beta 1.

BACKGROUND: Our previous results have showed that oral glutamine (GLN) supplementation decreased carcinogenesis in 7,12-dimethylbenz[a]antracene (DMBA) breast cancer model. We also have found that GLN raises blood glutathione (GSH) levels in an implantable breast cancer model. The process of tumor growth was accompanied by depressed GSH production and increased levels of insulin-like growth factor-I (IGF-I) and transforming growth factor beta1 (TGF-beta 1). GSH is counter-regulatory to IGF-I. We therefore hypothesized that in DMBA model of breast cancer, the increased GSH levels seen with oral GLN would be associated with lowered levels of IGF-I &TGF-beta(1). METHODS: Time-dated pubertal Sprague-Dawley rats were gavaged at time 0 with 1 g/kg/day glutamine (GLN) (n = 18), isonitrogenous Freamine (FA) (n = 18), or water (H(2)O) (n = 18). Rats were further randomized on day 7 to 100 mg/kg DMBA or oil. After 14 days, the animals were sacrificed and blood GSH, IGF-1, TGF-beta 1, breast tissue, and gut mucosa GSH levels were measured. RESULTS: Oral GLN increased significantly blood, breast tissue, and gut mucosa levels of GSH in both DMBA and control groups in comparison with the control groups not treated with GLN. At the same time, the levels of blood IGF-I and TGF-beta 1 decreased significantly in both DMBA-treated and control groups. DMBA did not significantly affect any of these levels. CONCLUSIONS ;Oral GLN increased GSH levels and lowered IGF-I and TGF-beta 1 in a range that is considered clinically significant. However, the effect of GLN in maintaining normal gut GSH production in the presence of DMBA was much more significant. Inconsistent with our hypothesis, reduction in IGF and TGF-beta 1 levels did not correlate with DMBA's effect on gut GSH production.