Secretin-dependent signals in the ventromedial hypothalamus regulate energy metabolism and bone homeostasis in mice.

Secretin, though originally discovered as a gut-derived hormone, is recently found to be abundantly expressed in the ventromedial hypothalamus, from which the central neural system controls satiety, energy metabolism, and bone homeostasis. However, the functional significance of secretin in the ventromedial hypothalamus remains unclear. Here we show that the loss of ventromedial hypothalamus-derived secretin leads to osteopenia in male and female mice, which is primarily induced by diminished cAMP response element-binding protein phosphorylation and upregulation in peripheral sympathetic activity. Moreover, the ventromedial hypothalamus-secretin inhibition also contributes to hyperphagia, dysregulated lipogenesis, and impaired thermogenesis, resulting in obesity in male and female mice. Conversely, overexpression of secretin in the ventromedial hypothalamus promotes bone mass accrual in mice of both sexes. Collectively, our findings identify an unappreciated secretin signaling in the central neural system for the regulation of energy and bone metabolism, which may serve as a new target for the clinical management of obesity and osteoporosis.

Virtual Reality-Based Intervention to Reduce Preoperative Anxiety in Adults Undergoing Elective Surgery: A Randomized Clinical Trial.

IMPORTANCE: Preoperative anxiety is common among adult patients undergoing elective surgery and is associated with negative outcomes. Virtual reality (VR)-based interventions have been considered simpler, safer, and more effective for reducing anxiety in patients undergoing surgery than conventional care. OBJECTIVE: To examine the effectiveness of a VR-based intervention with preoperative education in reducing preoperative anxiety among adult patients undergoing elective surgery. DESIGN, SETTING, AND PARTICIPANTS: An assessor-blinded prospective randomized clinical trial was conducted to recruit adult patients aged 18 years or older who were scheduled for their first elective surgery procedure under general anesthesia within the next 2 to 4 weeks at a preanesthesia assessment clinic in Hong Kong from July to December 2022. INTERVENTIONS: Participants were randomly assigned to either an intervention group (an 8-minute immersive 360° VR video tour in the operating theater via a head-mounted display console) or a control group (standard care). MAIN OUTCOMES AND MEASURES: The primary outcome of preoperative anxiety was measured using the Amsterdam Preoperative Anxiety and Information Scale (range, 6-30; higher scores indicate greater anxiety), and the secondary outcomes (ie, stress, preparedness, and pain) were assessed by Visual Analog Scale at 3 time points: baseline at beginning of clinical session (T0), at the end of the clinical session immediately after the intervention (T1), and before the surgery (T2). Pain, satisfaction levels, and postoperative length of stay were evaluated after the surgery (T3). Simulation sickness was assessed after the intervention by use of the Simulation Sickness Questionnaire. A generalized estimating equations model was applied to compare changes in outcomes over time. RESULTS: A total of 74 participants (mean [SD] age, 46.34 [14.52] years; 38 men [51.4%] and 36 women [48.6%]) were recruited and randomized to the control group (37 participants) and intervention group (37 participants). Compared with the control group, the VR-based intervention group showed significantly decreased preoperative anxiety at T1 (ß, -5.46; 95% CI, -7.60 to -3.32; P < .001) and T2 (ß, -5.57; 95% CI, -7.73 to -3.41; P < .001), lower stress at T1 (ß, -10.68; 95% CI, -16.00 to -5.36; P < .001) and T2 (ß, -5.16; 95% CI, -9.87 to -0.45; P = .03), and higher preparedness at T1 (ß, 6.60; 95% CI, 0.97 to 12.19; P = .02). Satisfaction levels were significantly increased in the intervention group vs the control group (mean [SD] score, 81.35 [9.24] vs 65.28 [8.16]; difference, 16.07; 95% CI, 12.00 to 20.15; P < .001). No significant differences in pain and postoperative length of stay were found. CONCLUSIONS AND RELEVANCE: The findings of this study suggest that a VR-based intervention is a feasible and effective way to reduce preoperative anxiety in adult patients undergoing elective surgery. Given the promising results of this study, further study in the form of large-scale, multicenter, randomized clinical trials with broader implementation is warranted. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR2100051690.

Inhibition of hypoxia-inducible factor-prolyl hydroxylation protects from cyclophosphamide-induced bladder injury and urinary dysfunction.

Disruption of the blood-urine barrier can result in acute or chronic inflammatory bladder injury. Activation of the oxygen-regulated hypoxia-inducible factor (HIF) pathway has been shown to protect mucosal membranes by increasing the expression of cytoprotective genes and by suppressing inflammation. The activity of HIF is controlled by prolyl hydroxylase domain (PHD) dioxygenases, which have been exploited as therapeutic targets for the treatment of anemia of chronic kidney disease. Here, we established a mouse model of acute cyclophosphamide (CYP)-induced blood-urine barrier disruption associated with inflammation and severe urinary dysfunction to investigate the HIF-PHD axis in inflammatory bladder injury. We found that systemic administration of dimethyloxalylglycine or molidustat, two small-molecule inhibitors of HIF-prolyl hydroxylases, profoundly mitigated CYP-induced bladder injury and inflammation as assessed by morphological analysis of transmural edema and urothelial integrity and by measuring tissue cytokine expression. Void spot analysis to examine bladder function quantitatively demonstrated that HIF-prolyl hydroxylase inhibitor administration normalized micturition patterns and protected against CYP-induced alteration of urinary frequency and micturition patterns. Our study highlights the therapeutic potential of HIF-activating small-molecule compounds for the prevention or therapy of bladder injury and urinary dysfunction due to blood-urine barrier disruption.NEW & NOTEWORTHY Disruption of the blood-urine barrier can result in acute or chronic inflammatory bladder injury. Here, we demonstrate that pharmacological inhibition of hypoxia-inducible factor (HIF)-prolyl hydroxylation prevented bladder injury and protected from urinary dysfunction in a mouse model of cyclophosphamide-induced disruption of the blood-urine barrier. Our study highlights a potential role for HIF-activating small-molecule compounds in the prevention or therapy of bladder injury and urinary dysfunction and provides a rationale for future clinical studies.

Update on Molecular Diagnosis in Extranodal NK/T-Cell Lymphoma and Its Role in the Era of Personalized Medicine.

Natural killer (NK)/T-cell lymphoma (NKTCL) is an aggressive malignancy with unique epidemiological, histological, molecular, and clinical characteristics. It occurs in two pathological forms, namely, extranodal NKTCL (ENKTCL) and aggressive NK leukemia, according to the latest World Health Organization (WHO) classification. Epstein-Barr virus (EBV) infection has long been proposed as the major etiology of lymphomagenesis. The adoption of high-throughput sequencing has allowed us to gain more insight into the molecular mechanisms of ENKTCL, which largely involve chromosome deletion and aberrations in Janus kinase (JAK)-signal transducer and activator of transcription (STAT), programmed cell death protein-1 (PD-1)/PD-ligand 1 (PD-L1) pathways, as well as mutations in tumor suppressor genes. The molecular findings could potentially influence the traditional chemoradiotherapy approach, which is known to be associated with significant toxicity. This article will review the latest molecular findings in NKTCL and recent advances in the field of molecular diagnosis in NKTCL. Issues of quality control and technical difficulties will also be discussed, along with future prospects in the molecular diagnosis and treatment of NKTCL.

A qualitative interview study on successful pregnancies in women with spina bifida.

BACKGROUND: Improvements in antenatal medicine and surgical management for conditions associated with spina bifida such as hydrocephalus have extended the lifespan for individuals with spina bifida (SB) into adulthood. Decisions and education regarding reproductive care and pregnancies for patients with spina bifida are increasingly important. Pregnancy in these patients can be particularly challenging due to physical limitations, previous abdominal surgery for urinary or bowel management and presence of a ventriculoperitoneal shunt. To date, little research has examined the unique challenges that women with spina bifida face during pregnancy. OBJECTIVE: The purpose of this descriptive study is to characterize the successful pregnancy histories of SB women and describe how pregnancy affected their mobility as well as bladder and bowel management. STUDY DESIGN: We conducted semi-structured interviews with women followed in our adult multidisciplinary SB clinic who previously had successful pregnancies. Questions regarding perinatal issues, obstetrical complications, urinary tract infections (UTI) and neurological changes were asked. Baseline mobility, bladder and bowel management were compared with changes during and after pregnancy. RESULTS: 121 women of childbearing age were followed per year by our adult multidisciplinary spina bifida clinic between 2009 and 2016. We identified 6 women who successfully carried 8 pregnancies to term. There were no miscarriages. Four women had ventriculoperitoneal (VP) shunts. No children were born with neural tube defects. Mean age at first pregnancy was 23.5 years. Average gestational age at delivery was 37 weeks. 50% of the women had a spontaneous vaginal delivery. Five of six women intended to get pregnant; only one patient consumed folic acid regularly prior to pregnancy. Two of six women had bladder augmentation surgery, one of whom had urologic changes during pregnancy that persisted after childbirth. The other patient had a concomitant bladder neck sling procedure and did not have urologic issues during pregnancy. 50% of the patients experienced bladder-bowel dysfunction during their pregnancy. While 67% patients had full baseline ambulatory function, 4 patients had decreased mobility and required additional assistance during pregnancy. All returned to their baseline functionality afterwards. CONCLUSION: Six of our patients had eight successful pregnancies, with no children born with neural tube defects. New changes to mobility, bladder and bowel management were experienced by over half of the women during their pregnancies. Future studies should focus on the role of multidisciplinary teams in reproductive health education and perinatal management of changes to activities of daily living during pregnancy in this population.

Human immunodeficiency virus-positive women's perspectives on breastfeeding with antiretrovirals: A qualitative evidence synthesis.

Human immunodeficiency virus (HIV)-positive women can breastfeed with minimal risk of mother-to-child transmission if taking antiretrovirals. Guidelines surrounding infant feeding for HIV-positive women have evolved several times over the last two decades. Our review aimed to explore perspectives of breastfeeding with antiretrovirals from HIV-positive women since the World Health Organization (2010) infant feeding and antiretroviral guidelines. HIV-positive pregnant and postnatal women from all countries/settings were eligible. HIV-positive women were either on an antiretroviral regimen at the time of the study, previously on an antiretroviral regimen, not initiated on a regimen yet, or enrolled in prevention of mother-to-child transmission (PMTCT) care. Quality assessment of all included studies were conducted. Four databases (CINAHL, EMBASE, MEDLINE and PsycINFO) were searched for studies conducted from January 2010 to October 2020. Nine papers were included in the review, of which two presented findings from the same study. Five analytical themes were developed via thematic synthesis: (1) awareness of breastfeeding with antiretrovirals, (2) turmoil of emotions, (3) coping mechanisms, (4) the intertwining of secret, stigma and support and (5) support needed. Support from family and health care professionals and coping approaches were important to overcome stigma and the emotional challenges of breastfeeding with antiretrovirals. Health care professionals should be familiar with the most updated national and local guidance surrounding infant feeding and antiretrovirals. Further research into interventions to encourage HIV-positive women to adhere and commit to lifelong antiretroviral treatment (Option B+) for breastfeeding is required.

Relatively speaking? Partners' and family members' views and experiences of supporting breastfeeding: a systematic review of qualitative evidence.

This review aimed to synthesize qualitative evidence of views and experiences of partners and other family members who provided breastfeeding support for a relative. The Joanna Briggs Institute (JBI) methodology for systematic reviews of qualitative evidence was followed. Seven databases: CINAHL, MEDLINE, EMBASE, PsycINFO, Scopus, Maternal and Infant Care, and Web of Science were searched. Partners and other family members (e.g. grandmothers, siblings) of women in any countries were included. Included papers were critically appraised. The JBI meta-aggregative approach was used to analyze data and form synthesized findings. Seventy-six papers from 74 studies were included. Five synthesized findings were: (i) spectrum of family members' breastfeeding knowledge, experiences and roles; (ii) the complexity of infant feeding decision making; (iii) the controversy of breastfeeding in front of others; (iv) impact of breastfeeding on family; and (v) it takes more than just family members: support for family members. Partners' and family members' views and experiences of breastfeeding support reflected multi-faceted personal, social, financial, cultural, religious, emotional, psychological, and societal factors of the support they provided (or not). Healthcare professionals should engage them in breastfeeding discussions with the woman, and offer tailored and practical guidance relevant to help them to appropriately support the woman. This article is part of the theme issue 'Multidisciplinary perspectives on social support and maternal-child health'.

A Rare, Unusual Presentation of Newberyite Urolithiasis in Adolescent Female -A Case Report and Review of Literature.

We report a rare case of newberyite (magnesium monohydrate phosphate trihydrate) urolithiasis in a young female with a past medical history significant for longstanding autoimmune hepatitis. She presented to the emergency department with newly diagnosed nephrolithiasis. Over the next 2 years, she had recurrent renal calculi and 3 urologic procedures. Notably, she did not have any history of urinary tract infections or genitourinary abnormalities. Her last stone analysis revealed the unusual combination of newberyite and ammonium acid urate. The pathophysiology of ammonium acid urate and newberyite stone formation as well as risk factors of development are discussed in this report.

Evolutionarily related small viral fusogens hijack distinct but modular actin nucleation pathways to drive cell-cell fusion.

Fusion-associated small transmembrane (FAST) proteins are a diverse family of nonstructural viral proteins. Once expressed on the plasma membrane of infected cells, they drive fusion with neighboring cells, increasing viral spread and pathogenicity. Unlike viral fusogens with tall ectodomains that pull two membranes together through conformational changes, FAST proteins have short fusogenic ectodomains that cannot bridge the intermembrane gap between neighboring cells. One orthoreovirus FAST protein, p14, has been shown to hijack the actin cytoskeleton to drive cell-cell fusion, but the actin adaptor-binding motif identified in p14 is not found in any other FAST protein. Here, we report that an evolutionarily divergent FAST protein, p22 from aquareovirus, also hijacks the actin cytoskeleton but does so through different adaptor proteins, Intersectin-1 and Cdc42, that trigger N-WASP-mediated branched actin assembly. We show that despite using different pathways, the cytoplasmic tail of p22 can replace that of p14 to create a potent chimeric fusogen, suggesting they are modular and play similar functional roles. When we directly couple p22 with the parallel filament nucleator formin instead of the branched actin nucleation promoting factor N-WASP, its ability to drive fusion is maintained, suggesting that localized mechanical pressure on the plasma membrane coupled to a membrane-disruptive ectodomain is sufficient to drive cell-cell fusion. This work points to a common biophysical strategy used by FAST proteins to push rather than pull membranes together to drive fusion, one that may be harnessed by other short fusogens responsible for physiological cell-cell fusion.

Let's Talk About Sex: Special Considerations in Reproductive Care and Sexual Education in Young Women With Spina Bifida.

Medical advances in the last several decades have allowed an increasing number of children with spina bifida to reach adolescence and adulthood. As they reach puberty, girls with spina bifida face unique social and health challenges to their sexuality, such as orthopedic restrictions, continence, and pelvic floor disorders. Recent research efforts have focused on better understanding female sexual desires, dysfunctions, and activity and the role of the physician in educating this vulnerable population. This article aims to summarize current literature on sexual function, knowledge gaps, and the importance of tailored sexual education from providers in women with spina bifida.

Data highlighting phenotypic diversity of urine-associated Escherichia coli isolates.

This article provides a reusable dataset describing detailed phenotypic and associated clinical parameters in n=303 clinical isolates of urinary Escherichia coli collected at Vanderbilt University Medical Center. De-identified clinical data collected with each isolate are detailed here and correlated to biofilm abundance and metabolomics data. Biofilm-abundance data were collected for each isolate under different in vitro conditions along with datasets quantifying biofilm abundance of each isolate under different conditions. Metabolomics data were collected from a subset of bacterial strains isolated from uncomplicated cases of cystitis or cases with no apparent symptoms accompanying colonization. For more insight, please see "Defining a Molecular Signature for Uropathogenic versus Urocolonizing Escherichia coli: The Status of the Field and New Clinical Opportunities" [1].

A viral fusogen hijacks the actin cytoskeleton to drive cell-cell fusion.

Cell-cell fusion, which is essential for tissue development and used by some viruses to form pathological syncytia, is typically driven by fusogenic membrane proteins with tall (>10 nm) ectodomains that undergo conformational changes to bring apposing membranes in close contact prior to fusion. Here we report that a viral fusogen with a short (<2 nm) ectodomain, the reptilian orthoreovirus p14, accomplishes the same task by hijacking the actin cytoskeleton. We show that phosphorylation of the cytoplasmic domain of p14 triggers N-WASP-mediated assembly of a branched actin network. Using p14 mutants, we demonstrate that fusion is abrogated when binding of an adaptor protein is prevented and that direct coupling of the fusogenic ectodomain to branched actin assembly is sufficient to drive cell-cell fusion. This work reveals how the actin cytoskeleton can be harnessed to overcome energetic barriers to cell-cell fusion.

The role of echocardiography in the diagnosis and management of a giant unruptured sinus of Valsalva aneurysm.

Sinus of Valsalva Aneurysm (SVA) is an aortic root anomaly, consisting of a lack of continuity between the aortic media and the aortic annulus, caused by a structural deficiency of muscular and elastic tissue. We present the case of a 49-year-oldman with atypical chest pain. Echocardiographic imaging described a giant unruptured aneurysm of the right sinus of Valsalva which was confirmed by cardiac computed tomography and coronary angiography. The obstruction of the right coronary artery without intravascular thrombosis and the compression of the right ventricular outflow tract with dynamic obstruction gradient represent the particularities of our case.

Novel Multi-Modal Analgesia Protocol Significantly Decreases Opioid Requirements in Inflatable Penile Prosthesis Patients.

BACKGROUND: Inflatable penile prosthesis (IPP) surgery is associated with significant perioperative pain that may reduce patient satisfaction. Though various pain management strategies have been proposed, most implanters manage postoperative patients with only prescription opioids. No protocol to date has been implemented and reported for pain management in IPP patients throughout the entire recovery process following surgery. AIM: Develop a multimodal analgesic (MMA) regimen consisting of perioperative administration of acetaminophen, meloxicam, and gabapentin with intraoperative local anesthetic injections, and compare post-operative pain control to a matched cohort of patients managed with an opioid-based (OB) regimen. METHODS: We retrospectively analyzed our prospectively maintained IPP database from November 2015-January 2018. The MMA protocol was instituted for all patients beginning June 2017, and these patients were matched in a 1:2 ratio to a cohort of eligible IPP patients managed through an OB protocol. Only patients receiving a 3-piece IPP were included; those with a history of narcotic dependence, neuropathy, or chronic non-steroidal anti-inflammatory drug use were excluded. Postoperative pain scores (visual analog scale) and opioid usage (total morphine equivalents [TME] in milligrams) were compared temporally in the post-anesthesia care unit, postoperative day (POD) 0, POD 1, and following discharge. OUTCOMES: The primary outcomes of the study are postoperative pain scores and narcotic usage. RESULTS: 57 patients were eligible for analysis: 19 (33%) and 38 (66%) in the MMA and OB groups, respectively. Groups were similar in demographics. MMA patients had significantly lower visual analog scale scores in post-anesthesia care unit, POD 0, or POD 1 (mean 0.84 vs 2.97, P = .01; 2.62 vs 4.73, P = .003; and 2.26 vs 4.0, P = .01, respectively) and used fewer narcotics on POD 0 (mean 4.08 vs 13.8 mg TME, P < .001) and POD 1 (mean 5.05 vs 25.1 mg TME, P < .001). MMA patients were discharged home with fewer narcotics (mean 12.7 vs 51.3 tabs, P < .001), and despite this, the MMA group needed less narcotic medication refills (11% vs 49%, P = .007). Neither group experienced a medication-related postoperative adverse event. CLINICAL IMPLICATIONS: Multimodal pain management allows for effective pain control with minimal side effects, enhancing recovery. STRENGTHS & LIMITATIONS: This is the first report to assess use of a multi-modal pain regimen on IPP recipients with demonstration of tangible benefit throughout the recovery process. Limitations include a single-surgeon and retrospective study design. CONCLUSION: In our rigorous assessment of IPP patients, implementation of a novel MMA protocol achieved equivalent and effective pain control, while resulting in substantially fewer narcotics throughout the entire post-operative period following IPP implantation. Tong CMC, Lucas J, Shah A, et al. Novel Multi-Modal Analgesia Protocol Significantly Decreases Opioid Requirements in Inflatable Penile Prosthesis Patients. J Sex Med 2018;15:1187-1194.

Acute Coronary Syndrome: An Unusual Consequence of GERD.

We report a case of an 83-year-old man with history of coronary artery disease and gastroesophageal reflux disease (GERD) who presented with sudden onset nocturnal dyspnea. He was diagnosed with non-ST elevation myocardial infarction based on the electrocardiographic changes and cardiac biomarker elevation. Cardiac catheterization revealed chronic three-vessel coronary artery disease, with 2 patent grafts and 2 chronically occluded grafts. While at the hospital, the patient experienced a similar episode of nocturnal dyspnea, prompting a barium esophagram, which was suggestive of a stricture in the distal esophagus from long-standing GERD. We hypothesized that he had myocardial ischemia due to increased oxygen demand from uncontrolled GERD symptoms. He had no further ischemic episodes after increasing the dose of antireflux medication over a 6-month follow-up. After presenting our case, we review the literature on this atypical presentation of GERD causing acute coronary syndrome and discuss potential mechanisms.

Lyme Carditis in the Fast Lane: From Alternating Bundle Branch Block to Asystole in 12 Hours.

Lyme borreliosis is a multisystem infectious disease with well-known cardiac involvement, including potential carditis as well as conduction abnormalities. We report a case of Lyme disease in a previously healthy 24-year-old male presenting with alternating right- and left-bundle branch block, indicating infra-Hisian atrioventricular (infra-His) block with an accelerated fascicular escape rhythm. Inless than 12 hours, the conduction abnormalities progressed to asystole requiring the urgent placement of a temporary transvenous pacemaker. Subsequently, with appropriate antibiotic treatment, the patient's conduction abnormalities resolved in a week without the need for a permanent pacemaker.

Physiotherapy beyond Our Borders: Investigating Ideal Competencies for Canadian Physiotherapists Working in Resource-Poor Countries.

PURPOSE: To explore the perspectives of Canadian physiotherapists with global health experience on the ideal competencies for Canadian physiotherapists working in resource-poor countries. METHOD: A qualitative interpretive methodology was used, and the Essential Competency Profile for Physiotherapists in Canada, 2009 (ECP), was employed as a starting point for investigation and analysis. Semi-structured one-on-one interviews (60-90 minutes) were conducted with 17 Canadian physiotherapists who have worked in resource-poor countries. Descriptive and thematic analyses were conducted collaboratively. RESULTS: The seven ECP roles-Expert, Communicator, Collaborator, Manager, Advocate, Scholarly Practitioner, and Professional-were all viewed as important for Canadian physiotherapists working in resource-poor countries. Two roles, Communicator and Manager, have additional competencies that participants felt were important. Three novel roles-Global Health Learner, Critical Thinker, and Respectful Guest-were created to describe other competencies related to global health deemed crucial by participants. CONCLUSIONS: This is the first study to examine competencies required by Canadian physiotherapists working in resource-poor countries. In addition to the ECP roles, supplementary competencies are recommended for engagement in resource-poor countries. These findings align with ideas in current global health and international development literature. Future research should examine the relevance of these findings to resource-poor settings within Canada.

Objectif : Analyser ce que les physiothérapeutes du Canada qui ont de l'expérience en santé dans le monde pensent des compétences idéales des physiothérapeutes canadiens œuvrant dans des pays pauvres en ressources. Méthode   : À partir d'une méthodologie d'interprétation qualitative et en nous fondant sur le Profil des compétences essentielles des physiothérapeutes au Canada, 2009 (CEP) comme point de départ de l'étude et de l'analyse, nous avons procédé à des entrevues personnelles et structurées (60 à 90 minutes) auprès de 17 physiothérapeutes du Canada qui ont travaillé dans des pays pauvres en ressources. Des analyses descriptives et thématiques ont été réalisées en collaboration. Résultats : Les sept rôles reliés aux CEP­expert, communicateur, collaborateur, gestionnaire, promoteur, érudit et professionnel­ont tous été considérés comme importants pour les physiothérapeutes canadiens qui travaillent dans des pays pauvres en ressources. Deux rôles, soit ceux de communicateur et de gestionnaire, comportent des compétences supplémentaires que les participants ont jugées importantes. Trois rôles nouveaux­apprenant en santé dans le monde, penseur critique et invité respectueux­ont été créés de façon à décrire d'autres compétences liées à la santé dans le monde jugées cruciales par les participants. Conclusions : Il s'agit de la première étude qui porte sur les compétences dont ont besoin les physiothérapeutes canadiens travaillant dans des pays pauvres en ressources. Outre les rôles reliés aux CEP, d'autres compétences sont recommandées pour travailler dans des pays pauvres en ressources. Ces constatations concordent avec les concepts que véhiculent des publications courantes sur la santé dans le monde et le développement international. Des recherches futures devraient porter sur la pertinence des constatations pour les contextes pauvres en ressources au Canada.

Functionalizable hydrogel microparticles of tunable size and stiffness for soft-tissue filler applications.

Particle size, stiffness and surface functionality are important in determining the injection site, safety and efficacy of injectable soft-tissue fillers. Methods to produce soft injectable biomaterials with controlled particle characteristics are therefore desirable. Here we report a method based on suspension photopolymerization and semi-interpenetrating network (semi-IPN) to synthesize soft, functionalizable, spherical hydrogel microparticles (MP) of independently tunable size and stiffness. MP were prepared using acrylated forms of polyethylene glycol (PEG), gelatin and hyaluronic acid. Semi-IPN MP of PEG-diacrylate and PEG were used to study the effect of process parameters on particle characteristics. The process parameters were systematically varied to produce MP with size ranging from 115 to 515µm and stiffness ranging from 190 to 1600Pa. In vitro studies showed that the MP thus prepared were cytocompatible. The ratio and identity of the polymers used to make the semi-IPN MP were varied to control their stiffness and to introduce amine groups for potential functionalization. Slow-release polymeric particles loaded with Rhodamine or dexamethasone were incorporated in the MP as a proof-of-principle of drug incorporation and release from the MP. This work has implications in preparing injectable biomaterials of natural or synthetic polymers for applications as soft-tissue fillers.