Using automated voice messages linked to telephone counselling to increase post-menstrual regulation contraceptive uptake and continuation in Bangladesh: study protocol for a randomised controlled trial.

BACKGROUND: Adoption of modern contraceptive methods after menstrual regulation (MR) is thought to reduce subsequent unwanted pregnancy and abortion. Long-acting reversible contraceptives (LARCs) are highly effective at reducing unintended pregnancy, but uptake in Bangladesh is low. Providing information on the most effective methods of contraception increases uptake of more effective methods. This protocol describes a randomised controlled trial of an intervention delivered by mobile phone designed to support post-MR contraceptive use in Bangladesh. METHODS: This is a multi-site single blind individual randomised controlled trial. At least 960 women undergoing MR procedures at selected facilities will be recruited after their procedure by female research assistants. Women will be randomised into the control or intervention group with a 1:1 ratio. All participants will receive usual clinic care, including contraceptive counselling and the telephone number of a non-toll-free call centre which provides counselling on MR and contraception. During the 4 months after their MR procedure, intervention participants will be sent 11 recorded interactive voice messages to their mobile phone about contraception with a focus on their chosen method and LARCs. Each message allows the participant to connect directly to the call centre. The intervention is free to the user. The control group will receive no messages delivered by mobile phone. All participants will be asked to complete an in-person questionnaire at recruitment and follow-up questionnaires by telephone at 2 weeks, 4 months and 12 months after their MR. The primary outcome for the trial will be self-reported LARC use 4 months post-MR. Secondary outcomes include LARC use at 2 weeks and 12 months post-MR, use of any effective modern contraceptive method at 2 weeks, 4 months and 12 months post-MR, and contraceptive discontinuation, contraceptive method switching, pregnancy, subsequent MR and experience of violence during the 12 month study period. DISCUSSION: Mobile phones offer a low-cost mechanism for providing individualised support to women with contraception outside of the clinic setting. This study will provide information on the effects of such an intervention among MR clients in Bangladesh. TRIAL REGISTRATION: Trial registered with clinicaltrials.gov Registration number: NCT02579785 Date of registration: 16th October 2015.

Integrating postabortion care, menstrual regulation and family planning services in Bangladesh: a pre-post evaluation.

BACKGROUND: In Bangladesh, abortion is restricted except to save the life of a woman, but menstrual regulation is allowed to induce menstruation and return to non-pregnancy after a missed period. MR services are typically provided through the Directorate General of Family Planning, while postabortion care services for incomplete abortion are provided by facilities under the Directorate General of Health Services. The bifurcated health system results in reduced quality of care, particularly for postabortion care patients whose procedures are often performed using sub-optimal uterine evacuation technology and typically do not receive postabortion contraceptive services. This study evaluated the success of a pilot project that aimed to integrate menstrual regulation, postabortion care and family planning services across six Directorate General of Health Services and Directorate General of Family Planning facilities by training providers on woman-centered abortion care and adding family planning services at sites offering postabortion care. METHODS: A pre-post evaluation was conducted in the six large intervention facilities. Structured client exit interviews were administered to all uterine evacuation clients presenting in the 2-week data collection period for each facility at baseline (n = 105; December 2011-January 2012) and endline (n = 107; February-March 2013). Primary outcomes included service integration indicators such as provision of menstrual regulation, postabortion care and family planning services in both facility types, and quality of care indicators such as provision of pain management, provider communication and women's satisfaction with the services received. Outcomes were compared between baseline and endline for Directorate General of Family Planning and Directorate General of Health Services facilities, and chi-square tests and t-tests were used to test for differences between baseline and endline. RESULTS: At the end of the project there was an increase in menstrual regulation service provision in Directorate General of Health Services facilities, from none at baseline to 44.1% of uterine evacuation services at endline (p < 0.001). The proportion of women accepting a postabortion contraceptive method increased from 14.3% at baseline to 69.2% at endline in Directorate General of Health Services facilities (p = 0.006). Provider communication and women's rating of the care they received increased significantly in both Directorate General of Health Services and Directorate General of Family Planning facilities. CONCLUSIONS: Integration of menstrual regulation, postabortion care and family planning services is feasible in Bangladesh over a relatively short period of time. The intervention's focus on woman-centered abortion care also improved quality of care. This model can be scaled up through the public health system to ensure women's access to safe uterine evacuation services across all facility types in Bangladesh.

'How shall we survive': a qualitative study of women's experiences following denial of menstrual regulation (MR) services in Bangladesh.

BACKGROUND: About one quarter of women in Bangladesh are denied menstrual regulation (MR) due to advanced gestation [J Fam Plann Reprod Health Care 41(3):161-163, 2015, Issues Brief (Alan Guttmacher Inst) (3):1-8, 2012]. Little is known about barriers to MR services, and whether women denied MR seek abortion elsewhere, self-induce, or continue the pregnancy. METHODS: After obtaining authorization from four health facilities in Bangladesh, we recruited eligible and interested women in to the study and requested informed consent for study participation. We conducted in-depth interviews with 20 women denied MR from four facilities in four districts in Bangladesh. Interviews were translated and transcribed, and the transcripts were analyzed by two researchers through an iterative process using a qualitative content analysis approach. RESULTS: Of those interviewed, 12 women sought abortion elsewhere and eight of these women were successful; four women who sought subsequent services were denied again. Two of the eight women who subsequently terminated their pregnancies suffered from complications. None of the participants were aware of the legal gestational limit for government-approved MR services. Given that all participants were initially denied services because they were beyond the legal gestational limit for MR and there were no reported risks to any of the mothers' health, we presume that the eight terminations performed subsequently were done illegally. CONCLUSIONS: Barriers to seeking safe MR services need to be addressed to reduce utilization of potentially unsafe alternative abortion services and to improve women's health and well being in Bangladesh. Findings from this study indicate a need to raise awareness about legal MR services; provide information to women on where, how and when they can access these services; train more MR providers; improve the quality and safety of second trimester services; and strengthen campaigns to educate women about contraception and pregnancy risk throughout the reproductive lifespan to prevent unintended pregnancies.

Women's experiences with medication for menstrual regulation in Bangladesh.

Menstrual regulation has been legal in Bangladesh since 1974, but the use of medication for menstrual regulation is new. In this study, we sought to understand women's experiences using medication for menstrual regulation in Bangladesh. We conducted 20 in-depth interviews with rural and urban women between December 2013 and February 2014. All interviews were audiotaped, transcribed, translated, computer recorded and coded for analysis. The majority of women in our study had had positive experiences with medication for menstrual regulation and successful outcomes, regardless of whether they obtained their medication from medicine sellers/pharmacies, doctors or clinics. Women were strongly influenced by health providers when deciding which method to use. There is a need to educate not only women of reproductive age, but also communities as a whole, about medication for menstrual regulation, with a particular emphasis on cost and branding the medication. Continued efforts to improve counselling by providers about the dose, medication and side-effects of medication for menstrual regulation, along with education of the community about medication as an option for menstrual regulation, will help to de-stigmatise the procedure and the women who seek it.

Self-Medication Practices among Adult Population in Bangladesh: A Cross-Sectional Study.

BACKGROUND: The practice of self-medication (SM) is common worldwide and is an important component of medical self-care. However, improper practice can be dangerous. This study aimed to estimate the prevalence of SM and the factors associated with it among Bangladeshi adults. METHODS: A cross-sectional survey was conducted between April and June 2021 among Bangladeshi adults (aged > 19 years) using convenient sampling. A total of 1320 subjects were collected through face-to-face interviews using a standardized questionnaire. Multivariable logistic regression analysis was used to identify factors associated with the practice of SM. RESULTS: Overall, 41% of adults in our survey reported SMP. The most common illnesses that prompted SM were common cold/flu (66.4%), gastric problems (65%), and headache (64.4%). The most frequent reasons for SM were to get better-perceived quality of care (30.6%), perceiving SM without side effects (23.3%), and saving time with effectiveness (14.56%). Potential risk factors included 10 years (AOR = 1.91; 95% CI: 1.04-3.50) and >12 years of schooling (AOR = 5.03; 95% CI: 2.27-11.15), being a businessman (AOR = 4.64; 95% CI: 1.74-12.37), having ≤6 family members (AOR = 2.13; 95% CI: 1.40-3.24), being a member of a social group (AOR = 1.53; 95% CI: 1.10-2.12), a health status check after every six months (AOR = 1.52; 95% CI: 1.08-2.13), and current ill-health (AOR = 1.41; 95% CI: 1.06-1.87). Protective factors identified included ≤30 years of age (AOR = 0.40; 95% CI: 0.17-0.93), and practice of modern (AOR = 0.39; 95% CI: 0.22-0.69) and herbal (AOR = 0.45; 95% CI: 0.21-0.97) treatment modality. CONCLUSION: More than one-third of the study participants reported practicing SM. Increasing the community's awareness of the adverse outcomes of SM and not just the average experience might sway individuals away from SM, and implementing strict jurisdiction could be a way to minimize inappropriate SM.

SMALL ACIDIC PROTEIN1 acts with RUB modification components, the COP9 signalosome, and AXR1 to regulate growth and development of Arabidopsis.

Previously, a dysfunction of the SMALL ACIDIC PROTEIN1 (SMAP1) gene was identified as the cause of the anti-auxin resistant1 (aar1) mutant of Arabidopsis (Arabidopsis thaliana). SMAP1 is involved in the response pathway of synthetic auxin, 2,4-dichlorophenoxyacetic acid, and functions upstream of the auxin/indole-3-acetic acid protein degradation step in auxin signaling. However, the exact mechanism by which SMAP1 functions in auxin signaling remains unknown. Here, we demonstrate that SMAP1 is required for normal plant growth and development and the root response to indole-3-acetic acid or methyl jasmonate in the auxin resistant1 (axr1) mutation background. Deletion analysis and green fluorescent protein/glutathione S-transferase pull-down assays showed that SMAP1 physically interacts with the CONSTITUTIVE PHOTOMORPHOGENIC9 SIGNALOSOME (CSN) via the SMAP1 F/D region. The extremely dwarf phenotype of the aar1-1 csn5a-1 double mutant confirms the functional role of SMAP1 in plant growth and development under limiting CSN functionality. Our findings suggest that SMAP1 is involved in the auxin response and possibly in other cullin-RING ubiquitin ligase-regulated signaling processes via its interaction with components associated with RELATED TO UBIQUITIN modification.

High-mobility group box-1 protein promotes granulomatous nephritis in adenine-induced nephropathy.

Granulomatous nephritis can be triggered by diverse factors and results in kidney failure. However, despite accumulating data about granulomatous inflammation, pathogenetic mechanisms in nephritis remain unclear. The DNA-binding high-mobility group box-1 protein (HMGB1) initiates and propagates inflammation when released by activated macrophages, and functions as an 'alarm cytokine' signaling tissue damage. In this study, we showed elevated HMGB1 expression in renal granulomas in rats with crystal-induced granulomatous nephritis caused by feeding an adenine-rich diet. HMGB1 levels were also raised in urine and serum, as well as in monocyte chemoattractant protein-1 (MCP-1), a mediator of granulomatous inflammation. Injection of HMGB1 worsened renal function and upregulated MCP-1 in rats with crystal-induced granulomatous nephritis. HMGB1 also induced MCP-1 secretion through mitogen-activated protein kinase (MAPK) and phosphoinositide-3-kinase (PI3K) pathways in rat renal tubular epithelial cells in vitro. Hmgb1(+/-) mice with crystal-induced nephritis displayed reduced MCP-1 expression in the kidneys and in urine and the number of macrophages in the kidneys was significantly decreased. We conclude that HMGB1 is a new mediator involved in crystal-induced nephritis that amplifies granulomatous inflammation in a cycle where MCP-1 attracts activated macrophages, resulting in excessive and sustained HMGB1 release. HMGB1 could be a novel target for inhibiting chronic granulomatous diseases.

Intraocular expression and release of high-mobility group box 1 protein in retinal detachment.

High-mobility group box 1 (HMGB1) protein is a multifunctional protein, which is mainly present in the nucleus and is released extracellularly by dying cells and/or activated immune cells. Although extracellular HMGB1 is thought to be a typical danger signal of tissue damage and is implicated in diverse diseases, its relevance to ocular diseases is mostly unknown. To determine whether HMGB1 contributes to the pathogenesis of retinal detachment (RD), which involves photoreceptor degeneration, we investigated the expression and release of HMGB1 both in a retinal cell death induced by excessive oxidative stress in vitro and in a rat model of RD-induced photoreceptor degeneration in vivo. In addition, we assessed the vitreous concentrations of HMGB1 and monocyte chemoattractant protein 1 (MCP-1) in human eyes with RD. We also explored the chemotactic activity of recombinant HMGB1 in a human retinal pigment epithelial (RPE) cell line. The results show that the nuclear HMGB1 in the retinal cell is augmented by death stress and upregulation appears to be required for cell survival, whereas extracellular release of HMGB1 is evident not only in retinal cell death in vitro but also in the rat model of RD in vivo. Furthermore, the vitreous level of HMGB1 is significantly increased and is correlated with that of MCP-1 in human eyes with RD. Recombinant HMGB1 induced RPE cell migration through an extracellular signal-regulated kinase-dependent mechanism in vitro. Our findings suggest that HMGB1 is a crucial nuclear protein and is released as a danger signal of retinal tissue damage. Extracellular HMGB1 might be an important mediator in RD, potentially acting as a chemotactic factor for RPE cell migration that would lead to an ocular pathological wound-healing response.

Minocycline attenuates both OGD-induced HMGB1 release and HMGB1-induced cell death in ischemic neuronal injury in PC12 cells.

High mobility group box-1 (HMGB1), a non-histone DNA-binding protein, is massively released into the extracellular space from neuronal cells after ischemic insult and exacerbates brain tissue damage in rats. Minocycline is a semisynthetic second-generation tetracycline antibiotic which has recently been shown to be a promising neuroprotective agent. In this study, we found that minocycline inhibited HMGB1 release in oxygen-glucose deprivation (OGD)-treated PC12 cells and triggered the activation of p38mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases (ERK1/2). The ERK kinase (MEK)1/2 inhibitor U-0126 and p38MAPK inhibitor SB203580 blocked HMGB1 release in response to OGD. Furthermore, HMGB1 triggered cell death in a dose-dependent fashion. Minocycline significantly rescued HMGB1-induced cell death in a dose-dependent manner. In light of recent observations as well as the good safety profile of minocycline in humans, we propose that minocycline might play a potent neuroprotective role through the inhibition of HMGB1-induced neuronal cell death in cerebral infarction.

Edaravone attenuates cerebral ischemic injury by suppressing aquaporin-4.

Aquaporin-4 (AQP4) plays a role in the generation of post-ischemic edema. Pharmacological modulation of AQP4 function may thus provide a novel therapeutic strategy for the treatment of stroke, tumor-associated edema, epilepsy, traumatic brain injury, and other disorders of the central nervous system (CNS) associated with altered brain water balance. Edaravone, a free radical scavenger, is used for the treatment of acute ischemic stroke (AIS) in Japan. In this study, edaravone significantly reduced the infarct area and improved the neurological deficit scores at 24h after reperfusion in a rat transient focal ischemia model. Furthermore, edaravone markedly reduced AQP4 immunoreactivity and protein levels in the cerebral infarct area. In light of observations that edaravone specifically inhibited AQP4 in a rat transient focal ischemia model, we propose that edaravone might reduce cerebral edema through the inhibition of AQP4 expression following cerebral infarction.

The free radical scavenger edaravone rescues rats from cerebral infarction by attenuating the release of high-mobility group box-1 in neuronal cells.

Edaravone, a potent free radical scavenger, is clinically used for the treatment of cerebral infarction in Japan. Here, we examined the effects of edaravone on the dynamics of high-mobility group box-1 (HMGB1), which is a key mediator of ischemic-induced brain damage, during a 48-h postischemia/reperfusion period in rats and in oxygen-glucose-deprived (OGD) PC12 cells. HMGB1 immunoreactivity was observed in both the cytoplasm and the periphery of cells in the cerebral infarction area 2 h after reperfusion. Intravenous administration of 3 and 6 mg/kg edaravone significantly inhibited nuclear translocation and HMGB1 release in the penumbra area and caused a 26.5 +/- 10.4 and 43.8 +/- 0.5% reduction, respectively, of the total infarct area at 24 h after reperfusion. Moreover, edaravone also decreased plasma HMGB1 levels. In vitro, edaravone dose-dependently (1-10 microM) suppressed OGD- and H(2)O(2)-induced HMGB1 release in PC12 cells. Furthermore, edaravone (3-30 microM) blocked HMGB1-triggered apoptosis in PC12 cells. Our findings suggest a novel neuroprotective mechanism for edaravone that abrogates the release of HMGB1.

Mechanism of HMGB1 release inhibition from RAW264.7 cells by oleanolic acid in Prunus mume Sieb. et Zucc.

High mobility group box-1 protein (HMGB1), primarily from the nucleus, is released into the extracellular milieu either passively from necrotic cells or actively through secretion by monocytes/macrophages. Extracellular HMGB1 acts as a potent inflammatory agent by promoting the release of cytokines such as tumor necrosis factor (TNF)-alpha, has procoagulant activity, and is involved in death due to sepsis. Accordingly, HMGB1 is an appropriate therapeutic target. In this study, we found that an extract of Prunus mume Sieb. et Zucc. (Ume) fruit (Ume extract), an abundant source of triterpenoids, strongly inhibited HMGB1 release from lipopolysaccharide (LPS)-stimulated macrophage-like RAW264.7 cells. The inhibitory effect on HMGB1 release was enhanced by authentic oleanolic acid (OA), a naturally occurring triterpenoid. Similarly, the HMGB1 release inhibitor in Ume extract was found to be OA. Regarding the mechanisms of the inhibition of HMGB1 release, the OA or Ume extract was found to activate the transcription factor Nrf2, which binds to the antioxidative responsive element, and subsequently the heme oxygenase (HO)-1 protein was induced, indicating that the inhibition of HMGB1 release from LPS-stimulated RAW264.7 cells was mediated via the Nrf2/HO-1 system; an essentially antioxidant effect. These results suggested that natural sources of triterpenoids warrant further evaluation as 'rescue' therapeutics for sepsis and other potentially fatal systemic inflammatory disorders.

Unintended Consequences of mHealth Interactive Voice Messages Promoting Contraceptive Use After Menstrual Regulation in Bangladesh: Intimate Partner Violence Results From a Randomized Controlled Trial.

BACKGROUND: Mobile phones for health (mHealth) hold promise for delivering behavioral interventions. We evaluated the effect of automated interactive voice messages promoting contraceptive use with a focus on long-acting reversible contraceptives (LARCs) among women in Bangladesh who had undergone menstrual regulation (MR), a procedure to "regulate the menstrual cycle when menstruation is absent for a short duration." METHODS: We recruited MR clients from 41 public- and private-sector clinics immediately after MR. Eligibility criteria included having a personal mobile phone and consenting to receive messages about family planning by phone. We randomized participants remotely to an intervention group that received at least 11 voice messages about contraception over 4 months or to a control group (no messages). The primary outcome was LARC use at 4 months. Adverse events measured included experience of intimate partner violence (IPV). Researchers recruiting participants and 1 analyst were blinded to allocation groups. All analyses were intention to treat. The trial is registered with ClinicalTrials.gov (NCT02579785). RESULTS: Between December 2015 and March 2016, 485 women were allocated to the intervention group and 484 to the control group. We completed follow-up on 389 intervention and 383 control participants. Forty-eight (12%) participants in the intervention group and 59 (15%) in the control group reported using a LARC method at 4 months (adjusted odds ratio [aOR] using multiple imputation=0.95; 95% confidence interval [CI]=0.49 to 1.83; P=.22). Reported physical IPV was higher in the intervention group: 42 (11%) intervention versus 25 (7%) control (aOR=1.97; 95% CI=1.12 to 3.46; P=.03) when measured using a closed question naming acts of violence. No violence was reported in response to an open question about effects of being in the study. CONCLUSIONS: The intervention did not increase LARC use but had an unintended consequence of increasing self-reported IPV. Researchers and health program designers should consider possible negative impacts when designing and evaluating mHealth and other reproductive health interventions. IPV must be measured using closed questions naming acts of violence.

Thrombomodulin exerts cytoprotective effect on low-dose UVB-irradiated HaCaT cells.

Thrombomodulin (TM) is an endothelial cell surface anticoagulant glycoprotein that performs antimetastatic, angiogenic, adhesive, and anti-inflammatory functions in various tissues. It is also expressed in epidermal keratinocytes. We found that a physiological dose (10mJ/cm(2)) of mid-wavelength ultraviolet irradiation (UVB) significantly induced TM expression via the p38mitogen-activated protein kinase (MAPK)/cyclic AMP response element (CRE) signaling pathway in the epidermal keratinocyte cell line HaCaT; this shows that TM regulates the survival of HaCaT cells. SB203580, a p38MAPK inhibitor, significantly decreased TM expression and the viability of cells exposed to UVB. Furthermore, overexpression of TM markedly increased cell viability, and it was abrogated by TM small interfering RNA (siRNA), suggesting that TM may play an important role in exerting cytoprotective effect on epidermal keratinocytes against low-dose UVB.

C-reactive protein induces high-mobility group box-1 protein release through activation of p38MAPK in macrophage RAW264.7 cells.

BACKGROUND: C-reactive protein (CRP) is widely used as a sensitive biomarker for inflammation. Increasing evidence suggests that CRP plays a role in inflammation. High-mobility group box-1 (HMGB1), a primarily nuclear protein, is passively released into the extracellular milieu by necrotic or damaged cells and is actively secreted by monocytes/macrophages. Extracellular HMGB1 as a potent inflammatory mediator has stimulated immense curiosity in the field of inflammation research. However, the molecular dialogue implicated between CRP and HMGB1 in delayed inflammatory processes remains to be explored. METHODS AND RESULTS: The levels of HMGB1 in culture supernatants were determined by Western blot analysis and enzyme-linked immunosorbent assay in macrophage RAW264.7 cells. Purified CRP induced the release of HMGB1 in a dose- and time-dependent fashion. Immunofluorescence analysis revealed nuclear translocation of HMGB1 in response to CRP. The binding of CRP to the Fc gamma receptor in RAW264.7 cells was confirmed by fluorescence-activated cell sorter analysis. Pretreatment of cells with IgG-Fc fragment, but not IgG-Fab fragment, efficiently blocked this binding. CRP triggered the activation of p38MAPK and ERK1/2, but not Jun N-terminal kinase. Moreover, both p38MAPK inhibitor SB203580 and small interfering RNA significantly suppressed the release of HMGB1, but not the MEK1/2 inhibitor U-0126. CONCLUSION: We demonstrated for the first time that CRP, a prominent risk marker for inflammation including atherosclerosis, could induce the active release of HMGB1 by RAW264.7 cells through Fc gamma receptor/p38MAPK signaling pathways, thus implying that CRP plays a crucial role in the induction, amplification, and prolongation of inflammatory processes, including atherosclerotic lesions.

Induction of high mobility group box 1 release from serotonin-stimulated human umbilical vein endothelial cells.

High mobility group box 1 (HMGB1) is a non-histone nuclear protein which is released from the nucleus of activated macrophages into the extracellular space in response to stimuli such as endotoxin or necrosis. The HMGB1 functions as a potent proinflammatory cytokine in the extracellular spaces. Recently, HMGB1 has been implicated in the progression of atherosclerosis. However, the association between HMGB1 and the development of atherosclerosis is poorly understood. Therefore, we examined whether serotonin (5-HT), a key factor involved in the development of atherosclerosis, induced HMGB1 release in human umbilical vein endothelial cells (HUVECs). We found that 5-HT induced the release of HMGB1 but not of ERK1/2 and JNK from HUVECs via the 5-HT receptor (5-HT1B)/p38 mitogen-activated protein kinase (MAPK) signaling pathway. The p38MAPK inhibitor SB203580 and the 5-HT1B antagonist GR55526 markedly inhibited HMGB1 release from 5-HT-stimulated HUVECs. The vascular endothelial growth factor (VEGF) derived from activated macrophages in atherosclerotic lesions also plays an important role in the progression of atherosclerosis. We found that HMGB1 induced VEGF production in macrophage-like RAW264.7 cells. HMGB1 induced the activation of p38MAPK, ERK1/2 and Akt. The PI3-kinase inhibitor LY294002 significantly inhibited VEGF production in HMGB1-stimulated macrophages, while other kinase inhibitors did not. These results suggest that HMGB1 release may contribute as a risk factor in the development and progression of atherosclerosis.

HMGB1 expression by activated vascular smooth muscle cells in advanced human atherosclerosis plaques.

BACKGROUND: Chronic inflammation plays a key role in atherogenesis, which is followed by atheromatous plaque instability. High-mobility group box 1 is released by activated macrophages as a late-phase mediator during prolonged inflammation. However, the expression of high-mobility group box 1 and its effect on the production of C-reactive protein and matrix metalloproteinases, particularly on human vascular smooth muscle cells, still remain unknown. METHODS AND RESULTS: Immunohistochemical studies revealed that high-mobility group box 1 was abundantly expressed in vascular smooth muscle cells of carotid and coronary atheromatous plaques, but not in atrophic vascular smooth muscle cells of fibrous plaques and normal medial vascular smooth muscle cells. Receptor for advanced glycation end products was also detected in vascular smooth muscle cells positive for high-mobility group box 1. Moreover, vascular smooth muscle cells positive for high-mobility group box 1 were found to express both C-reactive protein and matrix metalloproteinases (2, 3, and 9). Administration of exogenous high-mobility group box 1 to cultured vascular smooth muscle cells caused a marked elevation of C-reactive protein mRNA by reverse transcriptase-polymerase chain reaction and of C-reactive protein levels by enzyme-linked immunosorbent assay. Conversely, C-reactive protein also triggered a significant release of high-mobility group box 1 in vascular smooth muscle cell culture medium as determined by immunoblot. CONCLUSIONS: Activated vascular smooth muscle cells are the source of high-mobility group box 1 in human advanced atherosclerotic lesions. High-mobility group box 1 directly stimulates the production of both C-reactive protein and matrix metalloproteinase through receptor for advanced glycation end product. These findings provide new evidence that high-mobility group box 1 produced by activated vascular smooth muscle cells may contribute to the progression and vulnerability of human atherosclerotic lesions toward rupture.

Hydroxyapatite formed on/in agarose gel induces activation of blood coagulation and platelets aggregation.

We reported earlier that hydroxyapatite (HA) formed on/in agarose gels (HA/agarose) produced by alternate soaking process is a bone-filling material possessing osteoconductive and hemostatic effects. This process could allow us to make bone-like apatite that was formed on/in organic polymer hydrogel matrices. Here, we investigated the mechanism of hemostasis induced by HA/agarose and found that HA/agarose, but not agarose or HA powder, significantly shortened activated partial thromboplastin time (APTT). While HA/agarose did not show significant platelet aggregation, it markedly enhanced adenosine diphosphate (ADP)-induced platelet aggregation. Moreover, Western blot analysis revealed selective adsorption of vitronectin onto HA/agarose. We also observed marked differences between HA powder and HA/agarose in their XRD patterns. The crystallinity of HA powder was much higher compared to that of HA/agarose. Furthermore, 50-100 nm of tube-form aggregations was observed in HA powder on the other hand 100-200 nm of particles was observed in HA/agarose by SEM observation. Thus 100-200 nm of low crystallized particles on the surface structure of HA/agarose may play an important role in hemostasis. Our results demonstrated a crucial role of HA/agarose in the mechanism of hemostasis and suggested a potential role for HA/agarose as a bone-grafting material.

Developing mHealth Messages to Promote Postmenstrual Regulation Contraceptive Use in Bangladesh: Participatory Interview Study.

BACKGROUND: Abortions are restricted in Bangladesh, but menstrual regulation is an approved alternative, defined as a procedure of regulating the menstrual cycle when menstruation is absent for a short duration. Use of contraception after menstrual regulation can reduce subsequent unintended pregnancy, but in Bangladesh, the contraceptive method mix is dominated by short-term methods, which have higher discontinuation and failure rates. Mobile phones are a channel via which menstrual regulation clients could be offered contraceptive support after leaving the clinic. OBJECTIVE: This study aimed to support the development of a mobile phone intervention to support postmenstrual regulation family planning use in Bangladesh. It explored what family planning information women want to receive after having a menstrual regulation procedure, whether they would like to receive this information via their mobile phone, and if so, what their preferences are for the way in which it is delivered. METHODS: We conducted participatory interviews with 24 menstrual regulation clients in Dhaka and Sylhet divisions in Bangladesh. Women were recruited from facilities in urban and peri-urban areas, which included public sector clinics supported by Ipas, an international nongovernmental organization (NGO), and NGO clinics run by Marie Stopes. Main themes covered in the interviews were factors affecting the use of contraception, what information and support women want after their menstrual regulation procedure, how respondents would prefer to receive information about contraception, and other key issues for mobile health (mHealth) interventions, such as language and privacy. As part of the in-depth interviews, women were shown and played 6 different messages about contraception on the research assistant's phone, which they were given to operate, and were then asked to give feedback. RESULTS: Women were open to both receiving messages about family planning methods on their mobile phones and talking to a counselor about family planning methods over the phone after their menstrual regulation. Women most commonly wanted information about the contraceptive method they were currently using and wanted this information to be tailored to their particular needs. Women preferred voice messages to text and liked the interactive voice message format. When asked to repeat and identify the main points of the messages, women demonstrated good understanding of the content. Women did not seem too concerned with privacy or with others reading the messages and welcomed including their husbands in speaking to a counselor. CONCLUSIONS: This study found that menstrual regulation clients are very interested in receiving information on their phones to support family planning use and wanted more information about the method of contraception they were using. Participatory voicemail was the preferred modality.

Using mHealth to Support Postabortion Contraceptive Use: Results From a Feasibility Study in Urban Bangladesh.

BACKGROUND: As access to mobile technology improves in low- and middle-income countries, it becomes easier to provide information about sensitive issues, such as contraception and abortion. In Bangladesh, 97% of the population has access to a mobile signal, and the equity gap is closing in mobile phone ownership. Bangladesh has a high pregnancy termination rate and improving effective use of contraception after abortion is essential to reducing subsequent unwanted pregnancies. OBJECTIVE: This study examines the feasibility and acceptability of implementing a short message service (SMS) text message-based mHealth intervention to support postabortion contraceptive use among abortion clients in Bangladesh, including women's interest in the intervention, intervention preferences, and privacy concerns. METHODS: This feasibility study was conducted in four urban, high abortion caseload facilities. Women enrolled in the study were randomized into an intervention (n=60) or control group (n=60) using block randomization. Women completed a baseline interview on the day of their abortion procedure and a follow-up interview 4 months later (retention rate: 89.1%, 107/120). Women in the intervention group received text message reminders to use their selected postabortion contraceptive methods and reminders to contact the facility if they had problems or concerns with their method. Women who did not select a method received weekly messages that they could visit the clinic if they would like to start a method. Women in the control group did not receive any messages. RESULTS: Almost all women in the feasibility study reported using their mobile phones at least once per day (98.3%, 118/120) and 77.5% (93/120) used their phones for text messaging. In the intervention group, 87% (48/55) of women were using modern contraception at the 4-month follow-up, whereas 90% (47/52) were using contraception in the control group (P=.61). The intervention was not effective in increasing modern contraceptive use at follow-up, but 93% (51/55) of women reported at follow-up that the text reminders helped them use their method correctly and 76% (42/55) said they would sign up for this service again. Approximately half of the participants (53%, 29/55) said that someone they did not want to know about the text message reminders found out, mostly their husbands or children. CONCLUSIONS: In this small-scale feasibility study, text reminders did not increase postabortion contraceptive use. Despite the ineffectiveness of the text reminder intervention, implementation of a mHealth intervention among abortion clients in urban Bangladesh was feasible in that women were interested in receiving follow-up messages after their abortion and mobile phone use was common. Text messages may not be the best modality for a mHealth intervention due to relatively low baseline SMS text message use and privacy concerns.