The use of model constructs to design collaborative health information technologies: A case study to support child development.

OBJECTIVE: Health information technology could provide valuable support for inter-professional collaboration to address complex health issues, but current HIT systems do not adequately support such collaboration. Existing theoretical research on supporting collaborative work can help inform the design of collaborative HIT systems. Using the example of supporting collaboration between child development service providers, we describe a deductive approach that leverages concepts from the literature and analyzes qualitative user-needs data to aid in collaborative system design. MATERIALS AND METHODS: We use the Collaboration Space Model to guide the deductive qualitative analysis of interviews focused on the use of information technology to support child development. We deductively analyzed 44 interviews from two separate research initiatives and included data from a wide range of stakeholder groups including parents and various service providers. We summarized the deductively coded interview excerpts using quantitative and qualitative methods. RESULTS: The deductive analysis method provided a rich set of design data, highlighting heterogeneity in work processes, barriers to adequate communication, and gaps in stakeholder knowledge in supporting child development work. DISCUSSION: Deductive qualitative analysis considering constructs from a literature-based model provided useful, actionable data to aid in design. Design implications underscore functions needed to adequately share data across many stakeholders. More work is needed to validate our design implications and to better understand the situations where specific system features would be most useful. CONCLUSIONS: Deductive analysis considering model constructs provides a useful approach to designing collaborative HIT systems, allowing designers to consider both empirical user data and existing knowledge from the literature. This method has the potential to improve designs for collaborative HIT systems.

Effects of a novel carbocyclic analog of pyrrolo[2,3-d]pyrimidine nucleoside on pleiotropic induction of cell death in prostate cancer cells with different androgen responsiveness.

Prostate cancer is the most frequently diagnosed cancer and is one of the leading causes of male cancer death in the world. Recently, in the course of our screening for a novel anticancer compound, we synthesized carbocyclic analogs of pyrrolo[2,3-d]pyrimidine nucleoside; compounds 5, and 6. In the current study, we report the effects of compound 5 on pleiotropic induction of cell death via up-regulation of AR-associated p21(Cip1) protein in prostate cancer cells with different androgen responsiveness, such as LNCaP (androgen-dependent and -sensitive), LNCaP(C4-2) (androgen-independent and -sensitive; androgen-refractory), and DU145 (androgen-independent and -insensitive) cells. The treatment of LNCaP cells with 6 µM compound 5 for 24 h stimulated the androgen receptor (AR) activity and dramatically up-regulated transcription (56-fold) of p21(Cip1), which, in turn, induces typical apoptosis in the cells. However, induction of apoptosis through up-regulation (23-fold) of AR-associated p21(Cip1) achieved in LNCaP(C4-2) cells was possible by intensive cell treatment with compound 5 (9 µM, 48 h), because the cells are less sensitive and independent to androgen than LNCaP cells. Furthermore, 6 µM compound 5-treated DU145 cells, which exhibit extremely low AR activation due to no androgen responsiveness and dependency, showed neither up-regulation of p21(Cip1) nor apoptotic induction. Instead, a different type of cell death, autophagy-like death through the LC3B-associated autophagosome formation, was obviously induced in DU145 cells. Taken together, our results suggest that pleiotropic induction of prostate cancer cell death by compound 5 is determined by how efficiently and how abundantly androgen-dependent activation of the AR occurs, whereas compound 6 shows no induction of apoptosis in LNCaP cells.

High glucose condition induces autophagy in endothelial progenitor cells contributing to angiogenic impairment.

Cardiovascular complications are the major causes of death in patients with diabetes mellitus. Several studies have demonstrated that endothelial progenitor cells (EPCs), adult stem cells contributing to the regeneration of vascular endothelium, are dysfunctional under diabetic condition resulting in impaired peripheral circulation and delayed wound healing. In this study, we investigated the cellular alteration of EPCs under high glucose condition, to elucidate the mechanisms underlying diabetes-associated EPC dysfunction. EPCs were isolated from bone marrow and cultured in normal glucose (5.5 mM)- or high glucose (HG; 30 mM)-containing medium. High glucose treated-EPCs showed decreased ability to form tubule-like networks in Matrigel compared to EPCs under normal glucose, which matched well to the clinical observation of diabetic EPC dysfunction. Conversion of LC3-I to LC3-II was increased in EPCs under HG condition, showing that HG induced autophagy in EPCs. Flow cytometric analysis revealed generation of oxidative stress and disruption of mitochondrial permeability in HG exposed EPCs. Increased mitochondrial oxidative stress was also observed by mitochondria-specific superoxide indicator, MitoSOX(TM). Taken together, we demonstrated that autophagy and mitochondrial impairment were induced in EPCs under high glucose condition, giving a new insight into the mechanism underlying dysfunction of diabetic EPCs. We hope that our finding can contribute to the development of a new treatment option for cardiovascular complications in diabetic patients.

Communicating Bad News: Insights for the Design of Consumer Health Technologies.

BACKGROUND: As people increasingly receive personal health information through technology, there is increased importance for this information to be communicated with empathy and consideration for the patient's experience of consuming it. Although technology enables people to have more frequent and faster access to their health information, it could also cause unnecessary anxiety, distress, or confusion because of the sensitive and complex nature of the information and its potential to provide information that could be considered bad news. OBJECTIVE: The aim of this study was to uncover insights for the design of health information technologies that potentially communicate bad news about health such as the result of a diagnosis, increased risk for a chronic or terminal disease, or overall declining health. METHODS: On the basis of a review of established guidelines for clinicians on communicating bad news, we developed an interview guide and conducted interviews with patients, patients' family members, and clinicians on their experience of delivering and receiving the diagnosis of a serious disease. We then analyzed the data using a thematic analysis to identify overall themes from a perspective of identifying ways to translate these strategies to technology design. RESULTS: We describe qualitative results combining an analysis of the clinical guidelines for sharing bad health news with patients and interviews on clinicians' specific strategies to communicate bad news and the emotional and informational support that patients and their family members seek. Specific strategies clinicians use included preparing for the patients' visit, anticipating patients' feelings, building a partnership of trust with patients, acknowledging patients' physical and emotional discomfort, setting up a scene where patients can process the information, helping patients build resilience and giving hope, matching the level of information to the patients' level of understanding, communicating face-to-face, if possible, and using nonverbal means. Patient and family member experiences included internal turmoil and emotional distress when receiving bad news and emotional and informational support that patients and family members seek. CONCLUSIONS: The results from this study identify specific strategies for health information technologies to better promote empathic communication when they communicate concerning health news. We distill the findings from our study into design hypotheses for ways technologies may be able to help people better cope with the possibility of receiving bad health news, including tailoring the delivery of information to the patients' individual preferences, supporting interfaces for sharing patients' context, mitigating emotional stress from self-monitoring data, and identifying clear, actionable steps patients can take next.

p21CIP1 Induces Apoptosis via Binding to BCL2 in LNCaP Prostate Cancer Cells Treated with MCS-C3, A Novel Carbocyclic Analog of Pyrrolopyrimidine.

BACKGROUND: Previously, we synthesized a new carbocyclic analog of pyrrolo[2,3-d]pyrimidine nucleoside, designated MCS-C3. Recently, we found that LNCaP androgen-responsive prostate cancer cells treated with MCS-C3 rapidly undergo intrinsic apoptosis through dramatic up-regulation of p21(CIP1). The present study aimed to evaluate the cellular functions and underlying molecular mechanisms of p21(CIP1) on apoptotic induction in LNCaP cells treated with 6 µM MCS-C3. MATERIALS AND METHODS: Western blots, flow cytometric assay, immunoprecipitation, and transmission electron microscopy analysis were used to measure apoptotic induction in 6-µM MCS-C3-treated LNCaP cells. Effects of MCS-C3 on gene expression of p21(CIP1) were measured by semi-quantitative real-time polymerase chain reaction, and small interfering RNA transfection. RESULTS: MCS-C3 induced appreciable caspase-dependent apoptosis associated with the significant up-regulation of p53-dependent p21(CIP1) in LNCaP cells. Moreover, this apoptotic induction was caused by direct binding of p21(CIP1) to anti-apoptotic B-cell lymphoma 2 (BCL2) protein, and antagonizing BCL2 function. In addition, MCS-C3-mediated apoptotic induction, and up-regulation of p21(CIP1) were almost completely blocked by the treatment of androgen-responsive LNCaP cells with flutamide, an androgen receptor (AR) antagonist. CONCLUSION: We identified that induction of intrinsic apoptosis in LNCaP cells by 6 µM MCS-C3 is associated not only with p53 activation but also with mediation of AR. In the present study, we identified the cellular functions and underlying molecular mechanisms of p53-dependent and AR-associated p21(CIP1) on apoptotic induction via direct binding to BCL2 in LNCaP cells treated with 6 µM MCS-C3.

Baby Steps Text: Feasibility Study of an SMS-Based Tool for Tracking Children's Developmental Progress.

To help reach populations of children without consistent Internet access or medical care, we designed and implemented Baby Steps Text, an automated text message-based screening tool. We conducted preliminary user research via storyboarding and prototyping with target populations and then developed a fully functional system. In a one-month deployment study, we evaluated the feasibility of Baby Steps Text with fourteen families. During a one-month study, 13 out of 14 participants were able to learn and use the response structure (yielding 2.88% error rate) and complete a child development screener entirely via text messages. All post-study survey respondents agreed Baby Steps Text was understandable and easy to use, which was also confirmed through post-study interviews. Some survey respondents expressed liking Baby Steps Text because it was easy, quick, convenient to use, and delivered helpful, timely information. Our initial deployment study shows text messaging is a feasible tool for supporting parents in tracking and monitoring their child's development.

CR389, a benzoimidazolyl pyridinone analog, induces cell cycle arrest and apoptosis via p53 activation in human ovarian cancer PA-1 cells.

In the course of screening for novel cell cycle inhibitors and apoptotic inducers, CR389, elucidated as 5-(1H-benzoimidazol-2-yl)-1H-pyridin-2-one, was generated as a new hit compound. Flow cytometric analysis and western blots of PA-1 cells treated with 40 micrometer CR389 revealed an appreciable cell cycle arrest at the G2/M phase through direct inhibition of the CDK1 complex. In addition, activation of p53 via phosphorylation at Ser15 and subsequent up-regulation of p21(CIP1) showed that CR389 also induces p53-dependent-p21(CIP1)-mediated cell cycle arrest. Furthermore, apoptotic induction in 40 micrometer CR389-treated PA-1 cells is associated with the release of cytochrome c from mitochondria through up-regulation of the proapoptotic Bax protein, which results in the activation of procaspase-9 and -3, and the cleavage of poly(ADP-ribose) polymerase (PARP). Accordingly, CR389 seems to have multiple mechanisms of antiproliferative activity through p53-mediated pathways against human ovarian cancer cells. Therefore, we conclude that CR389 is a candidate therapeutic agent for the treatment of human ovarian cancer via the activation of p53.

HY253, a novel decahydrofluorene analog, induces apoptosis via intrinsic pathway and cell cycle arrest in liver cancer HepG2 cells.

Recently, we isolated HY253, a novel decahydrofluorene analog with a molecular structure of 7,8a-divinyl-2,4a,4b,5,6,7,8,8a,9,9a-decahydro-1H-fluorene-2,4a,4b,9a-tetraol from the roots of Aralia continentalis, which is known as Dokwhal, a traditional medicinal herb. Moreover, we previously reported its cytotoxic activity on cancer cell proliferation in human lung cancer A549 and cervical cancer HeLa cells. The current study aimed to evaluate its detailed molecular mechanisms in cell cycle arrest and apoptotic induction in human hepatocellular carcinoma HepG2 cells. Flow cytometric analysis of HepG2 cells treated with 60 micrometer HY253 revealed appreciable cell cycle arrest at the G1 phase via inhibition of Rb phosphorylation and down-regulation of cyclin D1. Furthermore, using western blots, we found that up-regulation of cyclin-dependent kinase inhibitors, such as p21(CIP1) and p27(KIP1), was associated with this G1 phase arrest. Moreover, TUNEL assay and immunoblottings revealed apoptotic induction in HepG2 cells treated with 100 micrometer HY253 for 24 h, which is associated with cytochrome c release from mitochondria, via down-regulation of anti-apoptotic Bcl-2 protein, which in turn resulted in activation of caspase-9 and -3, and proteolytic cleavage of poly(ADP-ribose) polymerase (PARP). Accordingly, we suggest that HY253 may be a potent chemotherapeutic hit compound for treating human liver cancer cells via up-regulation and activation of the p53 gene.

GALAXY EVOLUTION. An over-massive black hole in a typical star-forming galaxy, 2 billion years after the Big Bang.

Supermassive black holes (SMBHs) and their host galaxies are generally thought to coevolve, so that the SMBH achieves up to about 0.2 to 0.5% of the host galaxy mass in the present day. The radiation emitted from the growing SMBH is expected to affect star formation throughout the host galaxy. The relevance of this scenario at early cosmic epochs is not yet established. We present spectroscopic observations of a galaxy at redshift z = 3.328, which hosts an actively accreting, extremely massive BH, in its final stages of growth. The SMBH mass is roughly one-tenth the mass of the entire host galaxy, suggesting that it has grown much more efficiently than the host, contrary to models of synchronized coevolution. The host galaxy is forming stars at an intense rate, despite the presence of a SMBH-driven gas outflow.

HY251, a novel decahydrocyclopenta[a]indene analog, induces apoptosis via tBid-mediated intrinsic pathway in human ovarian cancer PA-1 cells.

We previously isolated a novel compound, HY251, with the molecular structure of 3-propyl-2-vinyl-1,2,3,3a,3b,6,7,7a,8,8adecahydrocyclopenta[ a]indene-3,3a,7a,8a-tetraol from the roots of Aralia continentalis. The current study was designed to evaluate the detailed molecular mechanisms underlying the apoptotic induction by HY251 in human ovarian cancer PA-1 cells. TUNEL assay and Western blot analyses revealed an appreciable apoptotic induction in PA-1 cells treated with 60 µM of HY251 for 24 h. This apoptotic induction was associated with caspase-8-dependent Bid cleavage, which in turn resulted in the formation of pro-apoptotic truncated Bid (tBid), and activation of caspase-9 and -3, as well as the cleavage of poly(ADP-ribose) polymerase (PARP). Moreover, we found that this death event was also associated with the significant upregulation and activation of the p53 tumor-suppressor protein through phosphorylation at Ser15. Therefore, we suggest that HY251 may be a potent cancer chemotherapeutic candidate for the treatment of ovarian cancer.

Benzyldihydroxyoctenone, a novel nonsteroidal antiandrogen, shows differential apoptotic induction in prostate cancer cells in response to their androgen responsiveness.

The molecular mechanisms of apoptotic induction by benzyldihydroxyoctenone (BDH), a nonsteroidal antiandrogen, isolated from the culture broth of Streptomyces sp., have been previously published in prostate cancer LNCaP cells. Apoptotic induction of BDH-treated LNCaP cells was associated with downregulation of Bcl-xL that caused, in turn, cytochrome c release from mitochondria, and activation of procaspases and specific proteolytic cleavage of poly(ADP-ribose) polymerase (PARP). The purpose of the present study was to investigate the patterns of apoptotic induction by BDH in non-prostate, ovarian cancer PA-1 (androgen-independent and -insensitive) cells and prostate cancer cells with different androgen responsiveness, such as C4-2 (androgen-independent and -sensitive), 22Rv1 (androgen-dependent and -low sensitive), and LNCaP (androgen-dependent and -high sensitive) cells. We found that BDH-treated LNCaP cell proliferation was significantly inhibited in a time-dependent manner and induced apoptosis via downregulation of the androgen receptor (AR) and prostate-specific antigen (PSA), as well as antiapoptotic Bcl-xL protein. However, the levels of BDH-mediated apoptotic induction and growth inhibition in 22Rv1 cells were apparently lower than those of LNCaP cells. In contrast, the induction of apoptosis and antiproliferative effect in BDH-treated non-prostate cancer PA-1 and hormone refractory C4-2 cells were not detectable and marginal, respectively. Therefore, BDH-mediated differential apoptotic induction and growth inhibition in a cell type seem to be obviously dependent on its androgen responsiveness; primarily on androgen-dependency, and then on androgen sensitivity.