Effectiveness of health literacy and relaxing music on quality of sleep and risk for antenatal depression.

Background: Pregnant women experience increased sleep disturbances during the third trimester of their pregnancy, which may result in the development of psychological issues in the perinatal period. There is a dearth of interventional studies that combine health literacy and the provision of music for the benefit of pregnant women in South Asia. Aim: To determine the effectiveness of a combination of Comprehensive Health literacy And Relaxing Music (CHARM) interventions on quality of sleep and risk for antenatal depression among women visiting antenatal outpatient departments of a tertiary hospital in South India. Methods: A four-arm parallel-group randomized controlled trial was adopted; 128 low-risk primigravid women were recruited and randomly assigned to the four groups using block randomization. The interventions included relaxing music interventions, comprehensive health-literacy interventions, combinations of both as CHARM interventions, and standard antenatal care. All the interventions were provided for four weeks. The quality of sleep among pregnant women was assessed using the Pittsburgh Sleep Quality Index Scale at baseline and after four weeks of intervention. Women at risk of developing antenatal depression were screened using the Edinburgh Postnatal Depression Scale-Antenatal Version. Results: Pregnant women who received CHARM interventions had significant improvement in quality of sleep when compared with other interventions (F(3,124) =15.0, P < .001, effect size η p2= 0.27). Also, 38 (29.6%) of the included pregnant women were at risk of developing antenatal depression, which was reduced to 21 (16.4%) following the intervention. Conclusion: CHARM intervention could promote quality sleep and reduce the risk of developing antenatal depression, thereby improving perinatal mental health.

Interventions to support contraceptive choice and use: a global systematic map of systematic reviews.

BACKGROUND: To review the highest level of available evidence, a systematic map identified systematic reviews that evaluated the effectiveness of interventions to improve contraception choice and increase contraception use. METHODS: Systematic reviews published since 2000 were identified from searches of nine databases. Data were extracted using a coding tool developed for this systematic map. Methodological quality of included reviews was assessed using AMSTAR 2 criteria. FINDINGS AND CONCLUSION: Fifty systematic reviews reported evaluations of interventions for contraception choice and use addressing three domains (individual, couples, community); Meta-analyses in 11 of the reviews mostly addressed interventions for individuals. We identified 26 reviews covering High Income Countries, 12 reviews covering Low Middle-Income Countries and the rest a mix of both. Most reviews (15) focussed on psychosocial interventions, followed by incentives (6) and m-health interventions (6). The strongest evidence from meta-analyses is for the effectiveness of motivational interviewing, contraceptive counselling, psychosocial interventions, school-based education, and interventions promoting contraceptive access, demand-generation interventions (community and facility based, financial mechanisms and mass media), and mobile phone message interventions. Even in resource constrained settings, community-based interventions can increase contraceptive use. There are gaps in the evidence on interventions for contraception choice and use, and limitations in study designs and lack of representativeness. Most approaches focus on individual women rather than couples or wider socio-cultural influences on contraception and fertility. This review identifies interventions which work to increase contraception choice and use, and these could be implemented in school, healthcare or community settings.

The utilization of systematic review evidence in formulating India's National Health Programme guidelines between 2007 and 2021.

Evidence-informed policymaking integrates the best available evidence on programme outcomes to guide decisions at all stages of the policy process and its importance becomes more pronounced in resource-constrained settings. In this paper, we have reviewed the use of systematic review evidence in framing National Health Programme (NHP) guidelines in India. We searched official websites of the different NHPs, linked to the main website of the Ministry of Health and Family Welfare (MoHFW), in December 2020 and January 2021. NHP guideline documents with systematic review evidence were identified and information on the use of this evidence was extracted. We classified the identified systematic review evidence according to its use in the guideline documents and analysed the data to provide information on the different factors and patterns linked to the use of systematic review evidence in these documents. Systematic reviews were mostly visible in guideline documents addressing maternal and newborn health, communicable diseases and immunization. These systematic reviews were cited in the guidelines to justify the need for action, to justify recommendations for action and opportunities for local adaptation, and to highlight implementation challenges and justify implementation strategies. Guideline documents addressing implementation cited systematic reviews about the problems and policy options more often than citing systematic reviews about implementation. Systematic reviews were linked directly to support statements in few guideline documents, and sometimes the reviews were not appropriately cited. Most of the systematic reviews providing information on the nature and scale of the policy problem included Indian data. It was seen that since 2014, India has been increasingly using systematic review evidence for public health policymaking, particularly for some of its high-priority NHPs. This complements the increasing investment in research synthesis centres and procedures to support evidence-informed decision making, demonstrating the continued evolution of India's evidence policy system.

Technology-based Comprehensive Cardiac Rehabilitation Therapy (TaCT) for women with cardiovascular disease in a middle-income setting: A randomized controlled trial protocol.

Women are underrepresented in cardiac rehabilitation (CR) despite the benefits, and this is exacerbated in lower-resource settings where CR is insufficiently available. In this randomized controlled trial, the effectiveness of the Technology-based Comprehensive Cardiac Rehabilitation Therapy (TaCT) electronic cardiac rehabilitation (eCR) intervention on functional capacity, risk factors, quality of life, heart-health behaviors, symptoms, and morbidity will be tested among women with CVD in a middle-income country. Following a pilot study, a single-center, single-blinded, 2 parallel-arm (1:1 SNOSE) superiority trial comparing an eCR intervention (TaCT) to usual care, with assessments pre-intervention and at 3 and 6 months will be undertaken. One hundred adult women will be recruited. Permuted block (size 10) randomization will be applied. The 6-month intervention comprises an app, website, SMS texts with generic heart-health management advice, and bi-weekly 1:1 telephone calls with a nurse trainee. Individualized exercise prescriptions will be developed based on an Incremental Shuttle Walk Test (primary outcome) and dietary plans based on 24 h dietary recall. A yoga/relaxation video will be provided via WhatsApp, along with tobacco cessation support and a moderated group chat. At 3 months, intervention engagement and acceptability will be assessed. Analyses will be conducted based on intent-to-treat. If results of this novel trial of women-focused eCR in a middle-income country demonstrate clinically-significant increases in functional capacity, this could represent an important development for the field considering this would be an important outcome for women and would translate to lower mortality.

Effectiveness of Music on Perinatal Anxiety Among Pregnant Women and Newborn Behaviors: A Systematic Review and Narrative Synthesis.

Background: Perinatal anxiety affects the antenatal woman, the growing fetus, and the newborn. This systematic review evaluated the effect of listening to music on perinatal anxiety among pregnant women and on newborn behaviors. No available reviews focus on interventions that include only classical forms of music or its benefit on perinatal anxiety among low-risk pregnant women or on newborn behaviors. Methods: We included peer-reviewed primary research studies on the effect of music on perinatal anxiety, published in English, between January 2010 and August 2022. PubMed, Embase, Scopus, and ProQuest were searched using specific keywords, resulting in 225 studies for screening by title, abstract, and full text. Two independent reviewers screened them and assessed the quality of the included randomized controlled trials (RCTs) using Cochrane's Risk of Bias 2.0 tool (RoB2) and non-randomized controlled trial studies using the Joanna Briggs Institute Critical Appraisal tool. Due to the heterogeneity of outcome measures, the review's findings were summarized qualitatively. Results: Nine studies with 1646 pregnant women and one with 260 pregnant women and their neonates were included. Results of all studies suggest that listening to classical music reduces the anxiety levels among pregnant women, as measured by the State-Trait Anxiety Inventory (STAI). Only one study reported the beneficial effect of antenatal exposure to music on improving newborn behaviors like orientation (ES 1.13, 95% CI: 0.82-1.44, P < 0.0001) and habituation (ES 1.05, 95% CI: 0.53-1.57, P = 0.0001). The risk of bias was unclear in most of the studies. Conclusions: Listening to classical music during the perinatal period may be an effective non-pharmacological intervention for reducing anxiety and pain and improving sleep quality and newborn behaviors. There is a need to conduct further interventional studies on the types of music provided and their effects on perinatal health outcomes. Registration of the Protocol: The review was prospectively registered in PROSPERO 2021 CRD42021256806.

Effectiveness of a peanut ball device during labour on maternal and neonatal outcomes: protocol for a randomised controlled trial.

Frequent positional changes and movements during labour is one of the recommendations by the World Health Organization (WHO) to prevent prolonged labour, thereby avoiding cesarean sections. However, labour induction, continuous fetal monitoring in supine position and immobilising the women during labour are standard practices in most private hospitals. To combat these problems and to implement WHO recommendations, the peanut ball is an effective device through which frequent positional changes will be achieved without disrupting the labour procedures. The current study aims to evaluate the effectiveness of the peanut ball device during labour on maternal and neonatal outcomes and assess the stress response induced by labour in terms of maternal and neonatal cortisol in low-risk primigravid women. The study is a prospective, block randomised controlled trial with parallel arms. A total of 768 study participants will be randomised to the peanut-ball group (intervention) and standard care group (control). The intervention group will receive different peanut ball positions during labour at or after 4 cm of cervical dilatation. The primary outcomes of the study are maternal outcome that includes measurement of duration of the active and the second stage of labour, stress level as measured by serum cortisol level at 3-4 cm and at 10 cm of cervical dilatation, mode of delivery, perception of pain, behavioural response during the active stage of labour and neonatal outcomes, which includes the pattern of fetal heart rate, APGAR score, birth injuries, and umbilical serum and salivary cortisol level. The collected data will be compared between the intervention and control groups.  Trial Registration: This research is registered under the CTRI (Clinical Trials Registry of India) ( CTRI/2019/08/020802) (21/8/2019).

An Evaluative Study to Assess the Effectiveness of a Video-Assisted Teaching Module on Knowledge and Practice Regarding Home-Based Colostomy Care of Children Among Primary Caregivers in Selected Hospital Lucknow, Uttar Pradesh.

INTRODUCTION: The aim of the study is to assess the knowledge and practice skills of home-based colostomy caregivers of children with a colostomy. The objective of the study was to assess the effectiveness of video teaching module on colostomy care among home-based colostomy caregivers. METHOD: A quasi-experimental study design and 30 samples were adopted. The samples selected by the purposive sampling technique those were fulfilled the sample criteria. Demographic and structured knowledge questionnaires were used for the data collection. RESULT: Descriptive and inferential statistics were used for data analysis by using SPSS software version 16.0. Out of 30 samples, demographic variables, 23 (76.6%) of the participants are of age between 21 and 30 years, 21 (70%) were housewives, 23 (76.6%) were mothers, 16 (53.4%) completed higher secondary, and 23 (76.6%) have monthly family income of INR 5001-10000. The majority of the children with a colostomy were toddler 22 (73.3%), gender ratio was equal, 27 (90%) are of Hindu religion, and 29 (96.7%) undergone colostomy. Knowledge score was divided based on percentage. Good knowledge scores in pre- and posttest are 0 and 29 (96.5%); moderate knowledge in pre- and posttest, 9 (30.5%) and 1 (3.3%); and poor knowledge in pre- vs posttest, 21(70%) and 0, respectively. Inferential statistics evaluated colostomy care video intervention. Knowledge was assessed by paired t test, - 19.607 (p < 0.05); similarly, practice skill assessed by Wilcoxon signed-rank was (z) - 4.716 (p < 0.01). CONCLUSION: Colostomy care video was a powerful tool to enhance primary caregivers' confidence, colostomy care skills, and attitude.

PROTOCOL: The effectiveness of social protection interventions in low- and middle-income countries: An evidence and gap map.

This evidence and gap map will provide an overview of the existing systematic reviews and impact evaluations on the key outcome domains and interventions aimed at improving social protection among people living in low- and middle-income countries (LMICs). The specific objectives of this map are to: (1) Develop a clear framework of types of interventions and outcomes related to the effectiveness of interventions on social protection for people in LMICs. (2) Map available systematic reviews and primary studies on the effectiveness of interventions on social protection for people in LMICs. (3) Provide a structured and accessible collection of existing evidence and identifying gaps in the available evidence on social protection intervention, thereby helping to inform the research agendas of funders and other organisations.

Impact of planned teaching program on the attitude of nurses with regard to patient rights in two multispecialty teaching hospitals in India.

BACKGROUND: The attitude of nurses with regard to patients' rights bears greater influence on its practice in the health-care settings. As health-care organizations grow toward standardization, positive changes in the attitude of health-care professionals are demanding. OBJECTIVES: The objectives of this study were to assess the attitude of nurses with regard to patient rights in two teaching hospitals, to devise a training program on patient rights for nurses, and to compare the impact of training with regard to patient rights on the attitude of nurses in two teaching hospitals. MATERIALS AND METHODS: This quasi-experimental study with one-group pre- and post-test research design for a sample of 200 nurses was carried out during the year 2017 at two multispecialty hospitals in India. The sample size was selected based on convenience sampling method. For the pretest, attitude was measured on a 5-point Likert scale through a questionnaire containing 27 items. Small-group teaching method was used to train nurses in groups of 8-10. Posttest was done through the same attitude questionnaire 1 week after the training program. RESULTS: In both the hospitals, the nurses had a favorable attitude toward patient rights before the training program; after training, majority of the nurses had the most favorable attitude toward patient rights. A statistically significant difference was observed in the attitude of nurses with regard to patient rights within the hospitals, before and after training nurses on patient rights (P < 0.001). CONCLUSIONS: Health-care organizations require developing planned teaching programs for nursing care professionals in order to influence their knowledge and attitude on patient rights. Their positive attitude toward patient rights leads to improved outcomes and effective nursing care practices.

Abnormal lipid processing but normal long-term repopulation potential of myc-/- hepatocytes.

Establishing c-Myc's (Myc) role in liver regeneration has proven difficult particularly since the traditional model of partial hepatectomy may provoke an insufficiently demanding proliferative stress. We used a model of hereditary tyrosinemia whereby the affected parenchyma can be gradually replaced by transplanted hepatocytes, which replicate 50-100-fold, over several months. Prior to transplantation, livers from myc-/- (KO) mice were smaller in young animals and larger in older animals relative to myc+/+ (WT) counterparts. KO mice also consumed more oxygen, produced more CO2 and generated more heat. Although WT and KO hepatocytes showed few mitochondrial structural differences, the latter demonstrated defective electron transport chain function. RNAseq revealed differences in transcripts encoding ribosomal subunits, cytochrome p450 members and enzymes for triglyceride and sterol biosynthesis. KO hepatocytes also accumulated neutral lipids. WT and KO hepatocytes repopulated recipient tyrosinemic livers equally well although the latter were associated with a pro-inflammatory hepatic environment that correlated with worsening lipid accumulation, its extracellular deposition and parenchymal oxidative damage. Our results show Myc to be dispensable for sustained in vivo hepatocyte proliferation but necessary for maintaining normal lipid homeostasis. myc-/- livers resemble those encountered in non-alcoholic fatty liver disease and, under sustained proliferative stress, gradually acquire the features of non-alcoholic steatohepatitis.

c-Myc and AMPK Control Cellular Energy Levels by Cooperatively Regulating Mitochondrial Structure and Function.

The c-Myc (Myc) oncoprotein and AMP-activated protein kinase (AMPK) regulate glycolysis and oxidative phosphorylation (Oxphos) although often for different purposes. Because Myc over-expression depletes ATP with the resultant activation of AMPK, we explored the potential co-dependency of and cross-talk between these proteins by comparing the consequences of acute Myc induction in ampk+/+ (WT) and ampk-/- (KO) murine embryo fibroblasts (MEFs). KO MEFs showed a higher basal rate of glycolysis than WT MEFs and an appropriate increase in response to activation of a Myc-estrogen receptor (MycER) fusion protein. However, KO MEFs had a diminished ability to increase Oxphos, mitochondrial mass and reactive oxygen species in response to MycER activation. Other differences between WT and KO MEFs, either in the basal state or following MycER induction, included abnormalities in electron transport chain function, levels of TCA cycle-related oxidoreductases and cytoplasmic and mitochondrial redox states. Transcriptional profiling of pathways pertinent to glycolysis, Oxphos and mitochondrial structure and function also uncovered significant differences between WT and KO MEFs and their response to MycER activation. Finally, an unbiased mass-spectrometry (MS)-based survey capable of quantifying ~40% of all mitochondrial proteins, showed about 15% of them to be AMPK- and/or Myc-dependent in their steady state. Significant differences in the activities of the rate-limiting enzymes pyruvate kinase and pyruvate dehydrogenase, which dictate pyruvate and acetyl coenzyme A abundance, were also differentially responsive to Myc and AMPK and could account for some of the differences in basal metabolite levels that were also detected by MS. Thus, Myc and AMPK are highly co-dependent and appear to engage in significant cross-talk across numerous pathways which support metabolic and ATP-generating functions.

Engineering of cell membranes with a bisphosphonate-containing polymer using ATRP synthesis for bone targeting.

The field of polymer-based membrane engineering has expanded since we first demonstrated the reaction of N-hydroxysuccinimide ester-terminated polymers with cells and tissues almost two decades ago. One remaining obstacle, especially for conjugation of polymers to cells, has been that exquisite control over polymer structure and functionality has not been used to influence the behavior of cells. Herein, we describe a multifunctional atom transfer radical polymerization initiator and its use to synthesize water-soluble polymers that are modified with bisphosphonate side chains and then covalently bound to the surface of live cells. The polymers contained between 1.7 and 3.1 bisphosphonates per chain and were shown to bind to hydroxyapatite crystals with kinetics similar to free bisphosphonate binding. We engineered the membranes of both HL-60 cells and mesenchymal stem cells in order to impart polymer-guided bone adhesion properties on the cells. Covalent coupling of the polymer to the non-adherent HL-60 cell line or mesenchymal stem cells was non-toxic by proliferation assays and enhanced the binding of these cells to bone.

Annexin II interactions with the annexin II receptor enhance multiple myeloma cell adhesion and growth in the bone marrow microenvironment.

Multiple myeloma (MM) is an incurable B-cell malignancy in which the marrow microenvironment plays a critical role in our inability to cure MM. Marrow stromal cells in the microenvironment support homing, lodging, and growth of MM cells through activation of multiple signaling pathways in both MM and stromal cells. Recently, we identified annexin II (AXII) as a previously unknown factor produced by stromal cells and osteoclasts (OCL) that is involved in OCL formation, HSC and prostate cancer (PCa) homing to the BM as well as mobilization of HSC and PCa cells. AXII expressed on stromal cells supports PCa cell lodgment via the AXII receptor (AXIIR) on PCa cells, but the role of AXII and AXIIR in MM is unknown. In this study, we show that MM cells express AXIIR, that stromal/osteoblast-derived AXII facilitates adhesion of MM cells to stromal cells via AXIIR, and OCL-derived AXII enhances MM cell growth. Finally, we demonstrate that AXII activates the ERK1/2 and AKT pathways in MM cells to enhance MM cell growth. These results demonstrate that AXII and AXIIR play important roles in MM and that targeting the AXII/AXIIR axis may be a novel therapeutic approach for MM.

Gfi1 expressed in bone marrow stromal cells is a novel osteoblast suppressor in patients with multiple myeloma bone disease.

Protracted inhibition of osteoblast (OB) differentiation characterizes multiple myeloma (MM) bone disease and persists even when patients are in long-term remission. However, the underlying pathophysiology for this prolonged OB suppression is unknown. Therefore, we developed a mouse MM model in which the bone marrow stromal cells (BMSCs) remained unresponsive to OB differentiation signals after removal of MM cells. We found that BMSCs from both MM-bearing mice and MM patients had increased levels of the transcriptional repressor Gfi1 compared with controls and that Gfi1 was a novel transcriptional repressor of the critical OB transcription factor Runx2. Trichostatin-A blocked the effects of Gfi1, suggesting that it induces epigenetic changes in the Runx2 promoter. MM-BMSC cell-cell contact was not required for MM cells to increase Gfi1 and repress Runx2 levels in MC-4 before OBs or naive primary BMSCs, and Gfi1 induction was blocked by anti-TNF-α and anti-IL-7 antibodies. Importantly, BMSCs isolated from Gfi1(-/-) mice were significantly resistant to MM-induced OB suppression. Strikingly, siRNA knockdown of Gfi1 in BMSCs from MM patients significantly restored expression of Runx2 and OB differentiation markers. Thus, Gfi1 may have an important role in prolonged MM-induced OB suppression and provide a new therapeutic target for MM bone disease.

HIP/RPL29 antagonizes VEGF and FGF2 stimulated angiogenesis by interfering with HS-dependent responses.

HIP/RPL29 is a heparan sulfate (HS) binding protein with diverse activities including modulation of heparanase (HPSE) activity. We examined HIP/RPL29's ability to modulate actions of HS-binding growth factors (HBGFs) in angiogenesis. Between 1 and 2.5 microg/ml (ca. 60-150 nM), HIP/RPL29 inhibited HBGF-stimulated endothelial cell tube formation. Aortic explant outgrowth also was inhibited, but at higher concentrations (40 microg/ml). At this concentration, HIP/RPL29 had no effect on HBGF-stimulated MAPK phosphorylation or VEGF-stimulated receptor-2 phosphorylation at site Y-996. Partial inhibition occurred at VEGF receptor-2 site Y951, associated with cell migration. HBGF displacement from HS-bearing perlecan domain I showed that HIP/RPL29 released 50% of bound HBGF at 20 microg/ml, a dose where endothelial tube formation is inhibited. Similar FGF2 release occurred at pH 5.0 and 7.0, conditions where HPSE is highly and residually active, respectively. We considered that HIP/RPL29 inhibits HPSE-dependent release of HS-bound HBGFs. At pH 5.0, release of soluble HS was inhibited by 64% at concentrations of 5 microg/ml and by 77% at 40 microg/ml, indicating that HIP/RPL29 antagonizes HPSE activity. At concentrations up to 40 microg/ml (ca. 2.5 microM) where angiogenic processes are inhibited, release of FGF2 occurred in the presence of HPSE and HIP/RPL29. The majority of this FGF2 is not bound to soluble HS. Studies of HIP/RPL29 binding to HS indicated that many structural features of HS are important in modulation of HBGF activities. Our findings suggest that inhibition of angiogenic processes by HIP/RPL29 involves attenuation of the formation of soluble, biologically active HBGF:HS complexes that activate HBGF receptors.

Decidual heparanase activity is increased during pregnancy in the baboon (Papio anubis) and in in vitro decidualization of human stromal cells.

Implantation is a complex process involving interactions between the embryo and the uterus. Adhesion, remodeling of the maternal vasculature, and decidualization are crucial events necessary for successful implantation to occur. Heparanase (HPSE), an endo-beta-D-glucuronidase, cleaves heparan sulfate at specific sites, leading to release of growth factors that may be involved in decidualization and remodeling of the maternal vasculature. HPSE also can function as a cell adhesion molecule. The aim of this study was to determine the expression of HPSE in the uteri of nonpregnant and pregnant baboons as well as in human stromal fibroblasts decidualized in vitro. We examined the localization and expression of HPSE using immunohistochemistry, Western blotting, RT-PCR, and activity assays. In nonpregnant baboon uteri, HPSE expression was localized to the apical surface of the glandular epithelia and in glandular secretions. However, in pregnant baboon uteri, HPSE was localized primarily in decidua. Uteri obtained at midpregnancy had higher heparanase activity compared with the nonpregnant uteri. A slight increase in HPSE expression was observed in human stromal fibroblasts decidualized in vitro. HPSE and HPSE2 mRNA transcripts were present in both decidualized tissue and cells. Increases in heparanase activity in the decidua from pregnant baboon uteri compared with tissue from nonpregnant animals and in human stromal fibroblasts decidualized in vitro suggest that HPSE plays a role in extracellular matrix remodeling and in increasing heparin-binding growth factor release during embryo implantation.

Heparan sulfate proteoglycans and their binding proteins in embryo implantation and placentation.

Complex interactions occur among embryonic, placental and maternal tissues during embryo implantation. Many of these interactions are controlled by growth factors, extracellular matrix and cell surface components that share the ability to bind heparan sulfate (HS) polysaccharides. HS is carried by several classes of cell surface and secreted proteins called HS proteoglycan that are expressed in restricted patterns during implantation and placentation. This review will discuss the expression of HS proteoglycans and various HS binding growth factors as well as extracellular matrix components and HS-modifying enzymes that can release HS-bound proteins in the context of implantation and placentation.

Heparanase expression and function during early pregnancy in mice.

Embryo implantation is a complex process that involves interactions between cell-surface and extracellular components of the blastocyst and the uterus, including blastocyst adhesion to the uterine luminal epithelium, epithelial basement membrane penetration and stromal extracellular matrix remodeling, angiogenesis, and decidualization. These processes all involve interactions with heparan sulfate (HS) proteoglycans, which harbor various growth factors and cytokines and support cell adhesion. Heparanase (HPSE) is an endo-beta-glucuronidase that cleaves HS at specific sites. HPSE also can act as an adhesion molecule independent of its catalytic activity. Thus, HPSE is a multifunctional molecule contributing to and modulating HS-dependent processes. Exogenously added HPSE improves embryo implantation in mice; however, no information is available regarding the normal pattern of HPSE expression and activity during the implantation process in any system. Using several approaches, including real-time RT-PCR, in situ hybridization, and immunohistochemistry, we determined that uterine HPSE expression increases dramatically during early pregnancy in mice. Heparanase mRNA and protein were primarily expressed in decidua and were rapidly induced at the implantation site. Uterine HPSE activity was characterized and demonstrated to increase >40-fold during early pregnancy. Finally, we demonstrate that the HPSE inhibitor PI-88 severely inhibits embryo implantation in vivo. Collectively, these results indicate that HPSE plays a role in blastocyst implantation and complements previous studies showing a role for HS-dependent interactions in this process.