Fatal Septic Shock Due to Aeromonas Hydrophila in a Cirrhotic Patient; a Case Report.

Aeromonas hydrophila has been identified as a causative agent of necrotizing fasciitis and myonecrosis, with most reported cases having a connection to aquatic-related trauma. Cases without such trauma history are rare in existing literature. Here, we present the case of a 56-year-old cirrhotic patient who lacked any prior aquatic-related trauma and arrived at the emergency department in a state of septic shock. The suspected route of entry was through necrotizing fasciitis and myonecrosis in his left forearm. Unfortunately, the patient succumbed to multi-organ failure and passed away within 12 hours of admission to the emergency department.

Successful introgression of wMel Wolbachia into Aedes aegypti populations in Fiji, Vanuatu and Kiribati.

Pacific Island countries have experienced periodic dengue, chikungunya and Zika outbreaks for decades. The prevention and control of these mosquito-borne diseases rely heavily on control of Aedes aegypti mosquitoes, which in most settings are the primary vector. Introgression of the intracellular bacterium Wolbachia pipientis (wMel strain) into Ae. aegypti populations reduces their vector competence and consequently lowers dengue incidence in the human population. Here we describe successful area-wide deployments of wMel-infected Ae. aegypti in Suva, Lautoka, Nadi (Fiji), Port Vila (Vanuatu) and South Tarawa (Kiribati). With community support, weekly releases of wMel-infected Ae. aegypti mosquitoes for between 2 to 5 months resulted in wMel introgression in nearly all locations. Long term monitoring confirmed a high, self-sustaining prevalence of wMel infecting mosquitoes in almost all deployment areas. Measurement of public health outcomes were disrupted by the Covid19 pandemic but are expected to emerge in the coming years.

An economic evaluation of Wolbachia deployments for dengue control in Vietnam.

INTRODUCTION: Dengue is a major public health challenge and a growing problem due to climate change. The release of Aedes aegypti mosquitoes infected with the intracellular bacterium Wolbachia is a novel form of vector control against dengue. However, there remains a need to evaluate the benefits of such an intervention at a large scale. In this paper, we evaluate the potential economic impact and cost-effectiveness of scaled Wolbachia deployments as a form of dengue control in Vietnam-targeted at the highest burden urban areas. METHODS: Ten settings within Vietnam were identified as priority locations for potential future Wolbachia deployments (using a population replacement strategy). The effectiveness of Wolbachia deployments in reducing the incidence of symptomatic dengue cases was assumed to be 75%. We assumed that the intervention would maintain this effectiveness for at least 20 years (but tested this assumption in the sensitivity analysis). A cost-utility analysis and cost-benefit analysis were conducted. RESULTS: From the health sector perspective, the Wolbachia intervention was projected to cost US$420 per disability-adjusted life year (DALY) averted. From the societal perspective, the overall cost-effectiveness ratio was negative, i.e. the economic benefits outweighed the costs. These results are contingent on the long-term effectiveness of Wolbachia releases being sustained for 20 years. However, the intervention was still classed as cost-effective across the majority of the settings when assuming only 10 years of benefits. CONCLUSION: Overall, we found that targeting high burden cities with Wolbachia deployments would be a cost-effective intervention in Vietnam and generate notable broader benefits besides health gains.

Infrastructure and Software Skills in the Expanded Program on Immunization at Commune Health Centers in Central Vietnam: A Cross-Sectional Mixed-Methods Study.

The application of the National Immunization Information System at primary health facilities is crucial in improving the quality of medical examinations as well as collecting and reporting immunization information. This study aimed to describe the infrastructure for the Expanded Program on Immunization's software at communes/wards/towns health centers (CHCs) of a province in central Vietnam and to evaluate the capacity of using immunization software of health officers. Another objective was to identify factors associated with skills in using the software of participants. A cross-sectional study combined with qualitative and quantitative methods was conducted, including 237 health officers from 50% (76/152) CHCs of Thua Thien Hue Province. Data were collected through face-to-face interviews using a developed questionnaire and observation via checklists. The results showed that most CHCs had sufficient infrastructure for the Expanded Program on Immunization (EPI). Health officers proficient in using the National Immunization Information System accounted for 74.7%. The CHCs should be equipped with more devices serving the immunization information management system and regularly maintain the equipment and the internet connection. Training health officers at CHCs in the data management of the vaccination system and record tracking ability using the National Immunization Information System is needed.

Two new chlorinated sesquiterpenes from Sigesbeckia orientalis.

Two new chlorinated guaianane-type sesquiterpenes (named chlosigesolides A and B) together with eight known compounds were isolated from the leaves and twigs of Sigesbeckia orientalis. Their structures were determined by analysis of HR-ESI-MS, 1D- and 2D-NMR spectral data as well as comparison with the literature. Absolute configurations of new compounds were elucidated by NOESY and ECD methods. Chlosigesolide A inhibited NO production in LPS-stimulated RAW264.7 macrophages with IC50 value of 10.9 ± 0.8 µM. Other compounds exhibited inhibitory activity at IC50 in range of 26.5 to 49.7 µM.

Periodontitis and Preeclampsia in Pregnancy: A Systematic Review and Meta-Analysis.

OBJECTIVES: A conflicting body of evidence suggests localized periodontal inflammation spreads systemically during pregnancy inducing adverse pregnancy outcomes. This systematic review and meta-analysis aim to specifically evaluate the relationship between periodontitis and preeclampsia. METHODS: Electronic searches were carried out in Medline, Pubmed, Embase, Lilacs, Cochrane Controlled Clinical Trial Register, CINAHL, ClinicalTrials.gov, and Google Scholar with no restrictions on the year of publication. We identified and selected observational case-control and cohort studies that analyzed the association between periodontal disease and preeclampsia. This meta-analysis was conducted following the PRISMA checklist and MOOSE checklist. Pooled odds ratios, mean difference, and 95% confidence intervals were calculated using the random effect model. Heterogeneity was tested with Cochran's Q statistic. RESULTS: Thirty studies including six cohort- and twenty-four case-control studies were selected. Periodontitis was significantly associated with increased risk for preeclampsia (OR 3.18, 95% CI 2.26 - 4.48, p < 0.00001), especially in a subgroup analysis including cohort studies (OR 4.19, 95% CI 2.23 - 7.87, p < 0.00001). The association was even stronger in a subgroup analysis with lower-middle-income countries (OR 6.70, 95% CI 2.61 - 17.19, p < 0.0001). CONCLUSIONS: Periodontitis appears as a significant risk factor for preeclampsia, which might be even more pronounced in lower-middle-income countries. Future studies to investigate if maternal amelioration of periodontitis prevents preeclampsia might be warranted.

Lead optimization of cathepsin K inhibitors for the treatment of Osteoarthritis.

Cathepsin K (Cat K) is a cysteine protease involved in bone remodeling. In addition to its role in bone biology, Cat K is upregulated in osteoclasts, chondrocytes and synoviocytes in osteoarthritic (OA) disease states making it a potential therapeutic target for disease-modifying OA. Starting from a prior preclinical compound, MK-1256, lead optimization efforts were carried out in the search for potent Cat K inhibitors with improved selectivity profiles with an emphasis on cathepsin F. Herein, we report the SAR studies which led to the discovery of the highly selective oxazole compound 23, which was subsequently shown to inhibit cathepsin K in vivo as measured by reduced levels of urinary C-telopeptide of collagen type I in dog.

A comprehensive study on the heterogeneous electro-Fenton degradation of tartrazine in water using CoFe2O4/carbon felt cathode.

In this study, cobalt ferrite coated carbon felt (CoFe2O4/CF) was synthesized by solvothermal method and applied as cathode for electro-Fenton (EF) treatment of tartrazine (TTZ) in water. The materials were characterized by SEM, XRD, FTIR, CV, and EIS to explore their physical, chemical, and electrical properties. The effects of solvothermal temperature and metal content on the TTZ removal were examined, showing that 220 °C with 2 mM of Co and 4 mM of Fe precursors were the best synthesis condition. Various influencing factors such as applied current density, pH, TTZ concentration, and electrolytes were investigated, and the optimal condition was found at 8.33 mA cm-2, pH 3, 50 mgTTZ L-1, and 50 mM of Na2SO4, respectively. By radical quenching test, , 1O2, and HO were recognized as the key reactive oxygen species and the reaction mechanism was proposed for the EF decolorization of TTZ using CoFe2O4/CF cathode. The reusability and stability test showed that the highly efficient CoFe2O4/CF cathode is very promising for practical application in wastewater treatment, especially for dyes and other recalcitrant organic compounds to improve its biodegradability.

Quality of life among advanced cancer patients in Vietnam: a multicenter cross-sectional study.

PURPOSE: Cancer is a leading cause of death in Vietnam. To maximize quality of life (QOL) at the end of life, valid and clinically useful instruments are needed to assess palliative care needs and the effectiveness of palliative care interventions. METHODS: We aimed to (i) determine psychometric properties of the Vietnamese version of the WHO abbreviated quality of life scale (WHOQOL-BREFVN) among advanced cancer patients, (ii) measure HR-QOL, and (iii) identify predictors of HR-QOL. We collected demographic, clinical, and HR-QOL data from stage III/IV adult cancer patients at two major Vietnamese cancer centers. We determined the internal consistency (Cronbach's alpha), construct validity (confirmatory factor analysis (CFA)), and discriminant validity (known-groups comparison) of the Vietnamese instrument. HR-QOL was analyzed descriptively. Multinomial logistic regressions identified predictors of HR-QOL. RESULTS: A total of 825 patients participated. Missing data were completely at random (MCAR) (chi-square = 14.270, df = 14, p = 0.430). Cronbach's alpha for all items was 0.904. CFA loadings of physical, psychological, social relationship, and environment domains onto HR-QOL were 0.81, 0.82, 0.34, and 0.75, respectively. Prediction of scores differed significantly by functional status (Wilks' lambda = 0.784, chi-square = 197.546, df = 4, p < 0.01, correct prediction = 74.6%). HR-QOL was reported as very bad/bad by n = 188 patients (22.8%) and general health as very bad/bad by n = 430 (52.1%). Multinomial logistic regression (likelihood ratio test: chi-square = 35.494, df = 24, p = 0.061, correct prediction = 62.2%) and the Pearson correlations revealed worse HR-QOL was associated with inpatient status, high ECOG score, and having dependent children. CONCLUSION: The Vietnamese version of the WHOQOL-BREF has excellent internal consistency reliability and sound construct and discriminant validity in advanced cancer patients. Advanced cancer inpatients, those with dependent children, and those with poorer physical function appear to have the greatest palliative care needs.

Preclinical evaluation of [11 C]L-235 as a radioligand for Positron Emission Tomography cathepsin K imaging in bone.

The cathepsin K (CatK) enzyme is abundantly expressed in osteoclasts, and CatK inhibitors have been developed for the treatment of osteoporosis. In our effort to support discovery and clinical evaluations of a CatK inhibitor, we sought to discover a radioligand to determine target engagement of the enzyme by therapeutic candidates using positron emission tomography (PET). L-235, a potent and selective CatK inhibitor, was labeled with carbon-11. PET imaging studies recording baseline distribution of [11 C]L-235, and chase and blocking studies using the selective CatK inhibitor MK-0674 were performed in juvenile and adult nonhuman primates (NHP) and ovariectomized rabbits. Retention of the PET tracer in regions expected to be osteoclast-rich compared with osteoclast-poor regions was examined. Increased retention of the radioligand was observed in osteoclast-rich regions of juvenile rabbits and NHP but not in the adult monkey or adult ovariectomized rabbit. Target engagement of CatK was observed in blocking studies with MK-0674, and the radioligand retention was shown to be sensitive to the level of MK-0674 exposure. [11 C]L-235 can assess target engagement of CatK in bone only in juvenile animals. [11 C]L-235 may be a useful tool for guiding the discovery of CatK inhibitors.

Effects of Odanacatib on Bone Structure and Quality in Postmenopausal Women With Osteoporosis: 5-Year Data From the Phase 3 Long-Term Odanacatib Fracture Trial (LOFT) and its Extension.

Odanacatib (ODN), a selective oral inhibitor of cathepsin K, was an investigational agent previously in development for the treatment of osteoporosis. In this analysis, the effects of ODN on bone remodeling/modeling and structure were examined in the randomized, double-blind, placebo-controlled, event-driven, Phase 3, Long-term Odanacatib Fracture Trial (LOFT; NCT00529373) and planned double-blind extension in postmenopausal women with osteoporosis. A total of 386 transilial bone biopsies, obtained from consenting patients at baseline (ODN n = 17, placebo n = 23), month 24 (ODN n = 112, placebo n = 104), month 36 (ODN n = 42, placebo n = 41), and month 60 (ODN n = 27, placebo n = 20) were assessed by dynamic and static bone histomorphometry. Patient characteristics at baseline and BMD changes over 5 years for this subset were comparable to the overall LOFT population. Qualitative assessment of biopsies revealed no abnormalities. Consistent with the mechanism of ODN, osteoclast number was higher with ODN versus placebo over time. Regarding bone remodeling, dynamic bone formation indices in trabecular, intracortical, and endocortical surfaces were generally similar in ODN-treated versus placebo-treated patients after 2 years of treatment. Regarding periosteal modeling, the proportion of patients with periosteal double labels and the bone formation indices increased over time in the ODN-treated patients compared with placebo. This finding supported the observed numerical increase in cortical thickness at month 60 versus placebo. In conclusion, ODN treatment for 5 years did not reduce bone remodeling and increased the proportion of patients with periosteal bone formation. These results are consistent with the mechanism of action of ODN, and are associated with continued BMD increases and reduced risk of fractures compared with placebo in the LOFT Phase 3 fracture trial. © 2020 American Society for Bone and Mineral Research.

Cathepsin K inhibition preserves compressive load in lumbar vertebrae of osteoporotic monkeys.

Anti-resorptive drugs treat bone loss by blocking osteoclast activity through a variety of mechanisms of action. Once significant bone loss has occurred, the ability to restore biomechanical function may differ based on the drug chosen. To assess this question, bisphosphonate (alendronate, ALN) and cathepsin K inhibitor (MK-0674, CatKi) were employed in treatment mode to compare the relative changes to cancellous bone microstructure and mechanical properties in ovariectomized (OVX) cynomolgus monkeys. Lumbar vertebrae (LV) bone mineral density (BMD) values taken two years post-surgery prior to drug treatment show a 10-15% decrease (p < 0.05) for all OVX animals. OVX animals were then treated with vehicle (VEH), ALN (0.03 mg/kg weekly), or CatKi MK-0674 (0.6 or 2.5 mg/kg daily, CatKi-L and H respectively) for two years and compared to a control Sham surgery group. Ex-vivo microcomputed tomography (µCT) of LV2 and compression testing of LV4-6 were used to measure cancellous bone microstructure and changes in bone mechanics, respectively. After two years of treatment, ALN-treated animals showed no significant difference in µCT or biomechanical parameters when compared to Veh. However, treatment with CatKi-H resulted in a 30% increase in yield and peak loads, and apparent peak and yield stress as compared to Veh (p < 0.05) and gave average mechanical values greater than the Sham sample. Treatment with CatKi-L exhibited a similar trend of increase to CatKi-H (p < 0.08). Intriguingly, these changes were realized despite no significant differences in mean values of trabecular bone morphologic parameters. Together these data suggest matrix-level changes in bone composition that are unique to the CatK inhibition mechanism, resulting in the preservation of bone compressive load with treatment.

Differing Effects of Parathyroid Hormone, Alendronate, and Odanacatib on Bone Formation and on the Mineralization Process in Intracortical and Endocortical Bone of Ovariectomized Rabbits.

Bone is formed by deposition of a collagen-containing matrix (osteoid) that hardens over time as mineral crystals accrue and are modified; this continues until bone remodeling renews that site. Pharmacological agents for osteoporosis differ in their effects on bone remodeling, and we hypothesized that they may differently modify bone mineral accrual. We, therefore, assessed newly formed bone in mature ovariectomized rabbits treated with the anti-resorptive bisphosphonate alendronate (ALN-100µ g/kg/2×/week), the anabolic parathyroid hormone (PTH (1-34)-15µ g/kg/5×/week), or the experimental anti-resorptive odanacatib (ODN 7.5 µM/day), which suppresses bone resorption without suppressing bone formation. Treatments were administered for 10 months commencing 6 months after ovariectomy (OVX). Strength testing, histomorphometry, and synchrotron Fourier-transform infrared microspectroscopy were used to measure bone strength, bone formation, and mineral accrual, respectively, in newly formed endocortical and intracortical bone. In Sham and OVX endocortical and intracortical bone, three modifications occurred as the bone matrix aged: mineral accrual (increase in mineral:matrix ratio), carbonate substitution (increase in carbonate:mineral ratio), and collagen molecular compaction (decrease in amide I:II ratio). ALN suppressed bone formation but mineral accrued normally at those sites where bone formation occurred. PTH stimulated bone formation on endocortical, periosteal, and intracortical bone surfaces, but mineral accrual and carbonate substitution were suppressed, particularly in intracortical bone. ODN treatment did not suppress bone formation, but newly deposited endocortical bone matured more slowly with ODN, and ODN-treated intracortical bone had less carbonate substitution than controls. In conclusion, these agents differ in their effects on the bone matrix. While ALN suppresses bone formation, it does not modify bone mineral accrual in endocortical or intracortical bone. While ODN does not suppress bone formation, it slows matrix maturation. PTH stimulates modelling-based bone formation not only on endocortical and trabecular surfaces, but may also do so in intracortical bone; at this site, new bone deposited contains less mineral than normal.

Articular cartilage protection in Ctsk-/- mice is associated with cellular and molecular changes in subchondral bone and cartilage matrix.

Osteoarthritis (OA) is a degenerative disease and a major cause of chronic disability in aging individuals. Cathepsin K (CatK), encoded by the Ctsk gene, has been implicated in the pathogenesis of pycnodysostosis and osteoporosis. The use of a selective inhibitor of CatK was recently shown to delay OA progression in rabbits. However, the cellular mechanisms underlying these protective effects remain unexplored. We examined articular cartilage maintenance and joint bone remodeling using Ctsk null mice (Ctsk-/- ) which underwent destabilization of the medial meniscus (DMM). We found that Ctsk-/- mice displayed delayed remodeling of subchondral and calcified cartilage by osteoclasts and chodroclasts respectively in DMM-induced osteoarthritis. While WT mice displayed a more severe OA phenotype than Ctsk-/- mice at 16 weeks, higher subchondral bone volume and lower trabecular spacing were also observed in surgically-induced OA joints of Ctsk-/- mice. However, no differences were seen in non-surgical controls. During OA progression, TRAP+ osteoclast numbers were increased in both WT and Ctsk-/- mice. However, Ctsk-/- mice had fewer physis-derived chondroclasts than WT when OA was present. These data suggest that CatK may differentially regulate chondroclastogenesis in the growth plate. Targeted PCR arrays of RNA harvested from laser captured osteoclasts in the subchondral bone and chondroclasts in the growth plate demonstrated differential expression of Atp6v0d2, Tnfrsf11a, Ca2, Calcr, Ccr1, Gpr68, Itgb3, Nfatc1, and Syk genes between WT and Ctsk-/- mice at 8- and 16-weeks post-DMM. Our data provide insight into the cellular mechanisms by which cathepsin K deletion delays OA progression in mice.

A novel role for cathepsin K in periosteal osteoclast precursors during fracture repair.

Osteoporosis management is currently centered around bisphosphonates, which inhibit osteoclast (OC) bone resorption but do not affect bone formation. This reduces fracture risk, but fails to restore healthy bone remodeling. Studies in animal models showed that cathepsin K (CatK) inhibition by genetic deletion or chemical inhibitors maintained bone formation while abrogating resorption during bone remodeling and stimulated periosteal bone modeling. Recently, periosteal mononuclear tartrate-resistant acid phosphatase-positive (TRAP+ ) osteoclast precursors (OCPs) were shown to augment angiogenesis-coupled osteogenesis. CatK gene deletion increased osteoblast differentiation via enhanced OCP and OC secretion of platelet-derived growth factor (PDGF)-BB and sphingosine 1 phosphate. The effects of periosteum-derived OCPs on bone remodeling are unknown, particularly with regard to fracture repair. We hypothesized that periosteal OCPs derived from CatK-null (Ctsk-/- ) mice may enhance periosteal bone formation during fracture repair. We found fewer periosteal OCPs in Ctsk-/- mice under homeostatic conditions; however, after fracture, this population increased in number relative to that seen in wild-type (WT) mice. Enhanced TRAP staining and greater expression of PDGF-BB were observed in fractured Ctsk-/- femurs relative to WT femurs. This early pattern of augmented PDGF-BB expression in Ctsk-/- mice may contribute to improved fracture healing by enhancing callus mineralization in Ctsk-/- mice.

Epidemiological, Serological, and Virological Features of Dengue in Nha Trang City, Vietnam.

Vietnam is endemic for dengue. We conducted a series of retrospective and prospective studies to characterize the epidemiology of dengue and population mobility patterns in Nha Trang city, Vietnam, with a view to rational design of trials of community-level interventions. A 10-year time series of dengue case notifications showed pronounced interannual variability, as well as spatial heterogeneity in ward-level dengue incidence (median annual coefficient of variation k = 0.47). Of 451 children aged 1-10 years enrolled in a cross-sectional serosurvey, almost one-third had evidence of a past dengue virus (DENV) infection, with older children more likely to have a multitypic response indicative of past exposure to ≥ 1 serotype. All four DENV serotypes were detected in hospitalized patients during 8 months of sampling in 2015. Mobility data collected from 1,000 children and young adults via prospective travel diaries showed that, although all ages spent approximately half of their daytime hours (5:00 am-9:00 pm) at home, younger age groups (≤ 14 years) spent a significantly greater proportion of their time within 500 m of home than older respondents. Together these findings inform the rational design of future trials of dengue preventive interventions in this setting by identifying 1) children < 7 years as an optimal target group for a flavivirus-naive serological cohort, 2) children and young adults as the predominant patient population for a study with a clinical end point of symptomatic dengue, and 3) substantial spatial and temporal variations in DENV transmission, with a consequent requirement for a trial to be large enough and of long enough duration to overcome this heterogeneity.

Thinning and drilling laser-assisted hatching in thawed embryo transfer: A randomized controlled trial / 대한생식의학회지

OBJECTIVE: In frozen and thawed embryos, the zona pellucida (ZP) can be damaged due to hardening. Laser-assisted hatching (LAH) of embryos can increase the pregnancy rate. This study compared thinning and drilling of the ZP before frozen embryo transfer (FET). METHODS: Patients were randomly allocated into two groups for LAH using thinning or drilling on day 2 after thawing. Twenty-five percent of the ZP circumference and 50% of the ZP thickness was removed in the thinning group, and a hole 40 µm in diameter was made in the drilling group. RESULTS: A total of 171 in vitro fertilization/intracytoplasmic sperm injection FET cycles, including 85 cycles with drilling LAH and 86 cycles with thinning LAH, were carried out. The thinning group had a similar β-human chorionic gonadotropin-positive rate (38.4% vs. 29.4%), implantation rate (16.5% vs. 14.4%), clinical pregnancy rate (36.0% vs. 25.9%), miscarriage rate (5.8% vs. 2.4%), ongoing pregnancy rate (30.2% vs. 23.5%), and multiple pregnancy rate (7.0% vs. 10.6%) to the drilling LAH group. There were no significant differences in pregnancy outcomes between subgroups defined based on age (older or younger than 35 years) or ZP thickness (greater or less than 17 µm) according to the LAH method. CONCLUSION: The present study demonstrated that partial ZP thinning or drilling resulted in similar outcomes in implantation and pregnancy rates using thawed embryos, irrespective of women's age or ZP thickness.

Metabolic Syndrome and Insulin Resistance Syndrome among Infertile Women with Polycystic Ovary Syndrome: A Cross-Sectional Study from Central Vietnam

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common endocrinopathies among reproductive-age women. Its metabolic features often overlap with those associated with metabolic syndrome (MS) and insulin resistance syndrome (IRS). The objective of this study was to determine the prevalence and predictors of MS and IRS in infertile Vietnamese women with PCOS. METHODS: A cross-sectional study was conducted at a tertiary fertility centre at Hue University Hospital from June 2016 to November 2017. A total of 441 infertile women diagnosed with PCOS based on the revised 2003 Rotterdam consensus criteria were enrolled. MS and IRS were defined based on the National Heart, Lung, and Blood Institute/American Heart Association Adult Treatment Panel III 2005 and American College of Endocrinology IRS 2003 criteria, respectively. Complete clinical and biochemical measurements of 318 women were available for analysis. Independent predictors of MS and IRS were identified using multivariate logistic regression. RESULTS: The overall prevalence of MS and IRS in women with PCOS was 10.4% and 27.0%, respectively. We identified older age (>30 years) and obesity as independent predictors of MS and IRS. Elevated anti-Müllerian hormone levels increased the risk of IRS, but not that of MS. CONCLUSION: MS and IRS are prevalent disorders among infertile Vietnamese women with PCOS. PCOS is not solely a reproductive problem. Screening and early intervention for MS and/or IRS based on anthropometric, metabolic, and reproductive hormone risk factors should be an integral part of fertility care.

Microstructure dependent binding of pigment epithelium derived factor (PEDF) to type I collagen fibrils.

Pigment epithelium derived factor (PEDF) is a multifunctional extracellular protein. In addition to its known anti-angiogenic and neurotrophic roles in collagen rich tissues, PEDF is thought to be involved in collagen fibril assembly due to its sequence specific binding to the collagen fibril and high expression in regions of active bone formation. In order to image the presence of the protein on the fibrils, PEDF was recombinantly made with a strep tag (strep-PEDF) and then gold nanoparticles conjugated to streptavidin (AuNP) were used as a secondary tag. The gold nanoparticles were detected using phase imaging in tapping mode AFM to image where exogenous PEDF bound in rabbit femur. These findings demonstrate that PEDF binds heterogeneously in cortical rabbit femur. Exogenous PEDF binding was concentrated at areas between microstructures with highly aligned collagen fibrils. Binding was not observed on or within the collagen fibrils themselves.

Long-term treatment with odanacatib maintains normal trabecular biomechanical properties in ovariectomized adult monkeys as demonstrated by micro-CT-based finite element analysis.

The cathepsin K inhibitor odanacatib (ODN) is a potent and reversible inhibitor of osteoclastic resorption activity. This drug is currently under development for the treatment of postmenopausal osteoporosis. Previously, we described data on the treatment efficacy of ODN in a preclinical estrogen-deficient model of an ovariectomized (OVX) rhesus monkey using HR-pQCT based finite element analysis (FEA) in vivo estimates of bone strength on the distal radius. To support the bone safety profile of ODN, we report ex vivo data on the apparent and hard tissue biomechanical properties of the trabecular bone of vertebrae of animals after 20 months of dosing in three treatment groups: Vehicle (VEH), ODN (2 mg/kg/day), and ALN (30 µg/kg/week). Biomechanical axial compression tests were performed on cylindrical trabecular samples cored out of the third lumbar vertebra of each animal at the end of the study. The biomechanical test results demonstrated that a normal (positive correlation between bone mineral density and bone strength) apparent material property relationship was maintained in the lumbar spine of ODN and ALN treated non-human primates (NHP). Trabecular bone hard tissue Young's modulus value was estimated using experimentally measured stiffness combined with FEA. The FEA and experimental results demonstrated that ODN treatment for 20 months maintained normal trabecular bone material hard tissue properties in the OVX-monkeys and was comparable to ALN.