Bladder and Bowel Symptoms, Dementia and Responsive Behaviors: An Integrative Review

Background: Dementia has become a worldwide healthcare and research focus. However, there is currently little research linking bladder and bowel symptoms with responsive behaviors in dementia. Aim: The aim of this integrative review was to identify research literature that explores the role of bladder and bowel symptoms as triggers of responsive behaviors  in persons with dementia. Design: This integrative review was informed by the method of Whittemore and Knafl and guidelines by Torraco. Methods: Electronic databases of Ovid Medline, Embase, PSYCInfo, Cochrane, EBSCO/CINAHL, Scopus, and Web of Science were searched. Five studies met inclusion criteria. They were assessed for quality using the Mixed Methods Appraisal Tool. Studies were compared, analyzed, and synthesized. Results: The categories developed were: (1) bladder and bowel symptoms examined, (2) relationship of behavior measurement to responsive behaviors, and (3) associations between incontinence and behaviors symptoms. Conclusion: The findings of this investigation demonstrate a limited understanding of the association between bladder and bowel symptoms with responsive behaviors. The conceptualization of behaviors as problems was evident in the studies. This conceptualization is not reflective of a contemporary view of behaviors as an expression of an unmet need. Future research is needed to understand the association between bladder and bowel symptoms and responsive behaviors

Alveolar macrophages lack CCR2 expression and do not migrate to CCL2

Background: The recruitment of mononuclear cells has important implications for tissue inflammation. Previous studies demonstrated enhanced CCR1 and CCR5 expression and decreased CCR2 expression during in vitro monocyte to macrophage differentiation. To date, no study examined the in vivo differences in chemokine receptor expression between human peripheral blood monocytes and alveolar macrophages. Methods: We examined the expression of these receptors in human peripheral blood monocytes and alveolar macrophages using microarray analysis, reverse-transcriptase PCR, flow cytometry and migration analyses. Results: In contrast to peripheral blood monocytes, alveolar macrophages did not express the CCL2 receptor, CCR2, and did not migrate toward CCL2. In contrast, monocytes and freshly isolated resident alveolar macrophages both migrated towards CCL3. However, up to 6-fold more monocytes migrated toward equivalent concentrations of CCL3 than did alveolar macrophages from the same donor. While peripheral blood monocytes expressed the CCL3 receptor, CCR1, alveolar macrophages expressed the alternate CCL3 receptor, CCR5. The addition of anti-CCR5 blocking antibodies completely abrogated CCL3-induced migration in alveolar macrophages, but did not affect the migration of peripheral blood monocytes. Conclusion: These data support the specificity of CCL2 to selectively drive monocyte, but not alveolar macrophage recruitment to the lung and CCR5 as the primary macrophage receptor for CCL3

Support System Effects on the DLR-F6 Transport Configuration in the National Transonic Facility

An experimental investigation of the DLR-F6 generic transport configuration was conducted in the NASA NTF for use in the Drag Prediction Workshop. As data from this experimental investigation was collected, a large difference in drag values was seen between the NTF test and an ONERA test that was conducted several years ago. After much investigation, it was determined that this difference was likely due to a sting effect correction applied to the ONERA data which NTF does not use. This insight led to the present work. In this study, a computational assessment has been undertaken to investigate model support system interference effects on the DLR-F6 transport configuration. The configurations computed during this investigation were the isolated wing-body, the wing-body with the full support system (blade and sting), the wing-body with just the blade, and the wing-body with just the sting. The results from this investigation show the same trends that ONERA saw when they conducted a similar experimental investigation in the S2MA tunnel. Computational results suggest that the blade contributed an interference type of effect, the sting contributed a general blockage effect, and the full support system combined these effects

A scale-out RDF molecule store for distributed processing of biomedical data

The computational analysis of protein-protein interaction and biomolecular pathway data paves the way to efficient in silico drug discovery and therapeutic target identification. However, relevant data sources are currently distributed across a wide range of disparate, large-scale, publicly-available databases and repositories and are described using a wide range of taxonomies and ontologies. Sophisticated integration, manipulation, processing and analysis of these datasets are required in order to reveal previously undiscovered interactions and pathways that will lead to the discovery of new drugs. The BioMANTA project focuses on utilizing Semantic Web technologies together with a scale-out architecture to tackle the above challenges and to provide efficient analysis, querying, and reasoning about protein-protein interaction data. This paper describes the initial results of the BioMANTA project. The fully-developed system will allow knowledge representation and processing that are not currently available in typical scale-out or Semantic Web databases. We present the design of the architecture, basic ontology and some implementation details that aim to provide efficient, scalable RDF storage and inferencing. The results of initial performance evaluation are also provided

Applicant perception of virtual interviews in cardiothoracic surgery: A Thoracic Education Cooperative Group Study

OBJECTIVES: Cardiothoracic programs used virtual interviews exclusively this year. As programs consider using virtual interviews permanently, our goal was to evaluate the experience of applicants with virtual interviews. METHODS: All 2020-2021 traditional cardiothoracic fellowship applicants received an anonymous electronic survey after the Match process ended. The survey assessed the number of interviews, strengths, and inadequacies of virtual interviews and factors that affected rank decision. RESULTS: Forty-three percent of applicants responded (60/139). The average number of interviews was 16.0. Eighty percent (48/60) of respondents successfully matched. Eighty-seven percent (52/60) of respondents had a favorable experience with virtual interviews, and 97% (58/60) found them to be convenient. However, only 50% (30/60) were able to evaluate a program fully. Respondents who matched were more likely to have a favorable experience (P = .02), but not more likely to be able to evaluate a program fully (P = .35). The most valued aspect was the informal meet and greet session with fellows (4.2 of 5). The least valued aspect was the program\u27s social media site (2.0 of 5). The factors most frequently used to decide ranking were case numbers by 92% (55/60) and culture/personality by 82% (49/60). CONCLUSIONS: Virtual interviews were perceived more favorably compared with last year, but half of applicants were still unable to evaluate a program fully. Fellow interactions were the most popular aspect of virtual interviews. As programs consider using virtual interviews permanently, more exposure to current trainees and a more robust social media/online presence will improve favorability

NAC and DTT promote TGF-β1 monomer formation: demonstration of competitive binding

TGF-β plays an important role in the genesis and progression of pulmonary fibrosis. We sought to determine the role of mononuclear phagocytes in the activation of TGF-β and found that freshly isolated peripheral blood monocytes spontaneously released TGF-β. Stimulating these monocytes with GM-CSF or LPS, but not MCSF, augmented the activation of TGF-β. In human monocytes, the free thiol compounds DTT and NAC decreased the activity of TGF-β, without affecting TGF-β mRNA transcription. Both NAC and DTT lessened the biological activity of recombinant active TGF-β in a cell-free system. We found that NAC and DTT reduced dimeric active TGF-β from a 25 kDa protein to 12.5 kDa inactive monomer. This conversion was reversed using the oxidizing agent diamide. Diamide also restored biological activity to NAC or DTT-treated TGF-β. Reduction of TGF-β to monomers could competitively inhibit active dimeric TGF-β and block intracellular signaling events. Our observations suggest that modulation of the oxidative state of TGF-β may be a novel therapeutic approach for patients with pulmonary fibrosis

Epithelial cell-directed efferocytosis in the post-partum mammary gland is necessary for tissue homeostasis and future lactation

<p>Abstract</p> <p>Background</p> <p>Mammary glands harbor a profound burden of apoptotic cells (ACs) during post-lactational involution, but little is known regarding mechanisms by which ACs are cleared from the mammary gland, or consequences if this process is interrupted. We investigated AC clearance, also termed efferocytosis, during post-lactational remodeling, using mice deficient for MerTK, Axl, and Tyro3, three related receptor tyrosine kinases (RTKs) regulating macrophage-mediated efferocytosis in monocytes. MerTK expression, apoptosis and the accumulation of apoptotic debris were examined in histological sections of MerTK-deficient, Axl/Tyro3-deficient, and wild-type mammary glands harvested at specific time points during lactation and synchronized involution. The ability of primary mammary epithelial cells (MECs) to engulf ACs was assessed in culture. Transplant of MerTK-deficient mammary epithelium into cleared WT mammary fat pads was used to assess the contribution of WT mammary macrophages to post-lactational efferocytosis.</p> <p>Results</p> <p>ACs induced MerTK expression in MECs, resulting in elevated MerTK levels at the earliest stages of involution. Loss of MerTK resulted in AC accumulation in post-lactational MerTK-deficient mammary glands, but not in Axl and Tyro3-deficient mammary glands. Increased vascularization, fibrosis, and epithelial hyperproliferation were observed in MerTK-deficient mammary glands through at least 60 days post-weaning, due to failed efferocytosis after lactation, but did not manifest in nulliparous mice. WT host-derived macrophages failed to rescue efferocytosis in transplanted MerTK-deficient mammary epithelium.</p> <p>Conclusion</p> <p>Efferocytosis by MECs through MerTK is crucial for mammary gland homeostasis and function during the post-lactational period. Efferocytosis by MECs thus limits pathologic consequences associated with the apoptotic load following lactation.</p

Parents’ motivations, concerns and understanding of genome sequencing: a qualitative interview study

Abstract: The 100,000 Genomes Project is a hybrid clinical and research project in which patients and parents are offered genome sequencing for cancer and rare and inherited disease diagnosis; all participants receive their main findings and contribute their data for research, and are offered optional secondary findings. Our aim was to explore participating parents’ attitudes towards and understanding of genome sequencing in this hybrid context. We conducted in-depth telephone interviews with 20 parents of children with rare diseases participating in the 100,000 Genomes Project. Parents were positive about contributing to research, although some had needed reassurance about data protections. Although most felt positive about secondary findings, some could not recall or misunderstood key aspects. Some were also concerned about potential emotional impact of results and a few raised concerns about life insurance implications, and the impact of future legal changes. Participants were generally positive about consent appointments, but several raised concerns about ‘information overload’ because of deciding about secondary findings at the same time as about the main diagnostic genome sequencing and data contribution. Additional information resources, particularly online tools, were highlighted as potentially useful ways of supporting the consent process. We conclude that parents offered genome sequencing as part of a national hybrid clinical and research project report many positive attitudes and experiences, but also concerns and misunderstandings. Further research is needed on how best to support informed consent, particularly about secondary findings. Additional resources such as online tools might usefully support future genome sequencing consent processes

Dysfunctional stem and progenitor cells impair fracture healing with age

Successful fracture healing requires the simultaneous regeneration of both the bone and vasculature; mesenchymal stem cells (MSCs) are directed to replace the bone tissue, while endothelial progenitor cells (EPCs) form the new vasculature that supplies blood to the fracture site. In the elderly, the healing process is slowed, partly due to decreased regenerative function of these stem and progenitor cells. MSCs from older individuals are impaired with regard to cell number, proliferative capacity, ability to migrate, and osteochondrogenic differentiation potential. The proliferation, migration and function of EPCs are also compromised with advanced age. Although the reasons for cellular dysfunction with age are complex and multidimensional, reduced expression of growth factors, accumulation of oxidative damage from reactive oxygen species, and altered signaling of the Sirtuin-1 pathway are contributing factors to aging at the cellular level of both MSCs and EPCs. Because of these geriatric-specific issues, effective treatment for fracture repair may require new therapeutic techniques to restore cellular function. Some suggested directions for potential treatments include cellular therapies, pharmacological agents, treatments targeting age-related molecular mechanisms, and physical therapeutics. Advanced age is the primary risk factor for a fracture, due to the low bone mass and inferior bone quality associated with aging; a better understanding of the dysfunctional behavior of the aging cell will provide a foundation for new treatments to decrease healing time and reduce the development of complications during the extended recovery from fracture healing in the elderly