Domiciliary dentistry clinics: a multiple case study in the province of Quebec, Canada.

BACKGROUND: The demand for more flexible and person-centered models of oral healthcare delivery is increasing and while mobile and domiciliary dental services have the potential to increase access to oral healthcare among dependent elderly and people with disabilities; the uptake of this service model by dentists remains low. Therefore, the aim of this study was to understand how existing domiciliary dental services operate within a particular context. METHODS: We used a qualitative descriptive multiple case study design. We studied three independent domiciliary dentistry clinics in the province of Quebec, Canada. We completed observations of 27 domiciliary visits, four of which were in private homes and the remaining 23 in LTCFs. We also conducted semi-structured interviews with dental professionals, patients, and caregivers. We performed a qualitative content analysis using a deductive/inductive coding framework. RESULTS: We presented a detailed description of the physical and service features of the studied cases. Physical features included the set-up of the mobile clinics, the portable equipment used, and the domiciliary locations of visits. For service features, we described the roles, attitudes, and interactions among those involved on both the providers' and recipients' sides, as well as, the logistical and financial aspect of the domiciliary dental services. CONCLUSIONS: Despite variations in setup and years of practice, the three mobile clinics had similar physical and service features. They also faced common logistic challenges but were able to provide services and respond to the high demand for domiciliary dental services. Additional research in different contexts would further contribute to building evidence-based models to help increase the uptake of this type of practice by current and future dental professionals.

Serum total periostin is an independent marker of overall survival in bone metastases of lung adenocarcinoma.

More than 35% of lung adenocarcinoma patients have bone metastases at diagnosis and have a poor survival. Periostin, a carboxylated matrix protein, mediates lung cancer cell dissemination by promoting epithelial-mesenchymal transition, and is involved in bone response to mechanical stress and bone formation regulation. This suggests that periostin may be used as a biomarker to predict survival in lung cancer patients. Serum periostin was assessed at diagnosis in a prospective cohort of 133 patients with lung adenocarcinoma of all stages. Patients were divided into localized and bone metastatic groups. Both groups were matched to healthy controls. Survival analysis and Cox proportional hazards models were conducted in the total population and in bone metastatic group. The median serum periostin level was higher in bone metastatic (n = 67; median: 1752 pmol/L) than in the localized group (n = 66; 861 pmol/L; p < 0.0001). Patients with high periostin (>median) had a poorer overall survival in the whole population (33.3 weeks vs. NR; p < 0.0001) and the bone metastatic group (24.4 vs. 66.1 weeks; p < 0.001). In multivariate analysis, patients with high periostin had increased risk of death (HR = 2.09, 95%CI [1.06-4.13]; p = 0.03). This was also found in the bone metastatic group (HR = 3.62, 95%CI [1.74-7.52]; p = 0.0005). Immunohistochemistry on bone metastasis biopsies showed periostin expression in the bone matrix and nuclear and cytoplasmic staining in cancer cells. Serum periostin was an independent survival biomarker in all-stage and in bone metastatic lung adenocarcinoma patients. IHC data suggest that periostin might be induced in cancer cells in bone metastatic niche in addition to bone microenvironment expression.

[Thromboembolic event and metabolic hyperhomocysteinemia: A case report and review of literature]. / Événement thromboembolique et hyperhomocystéinémie métabolique : case-report et revue de la littérature.

INTRODUCTION: Venous thromboembolic diseases have an incidence of 1.57/1000. Among patients under 50 years old, thrombophilia is assessed, the indications for which are increasingly stringent. Today, the need of plasma homocysteine assay is uncertain. OBSERVATION: Our case is a 42 year-old man, in whom a pulmonary embolism associated with macrocytosis made us discover a B12 deficiency secondary to Biermer's disease. In the literature, patients are men with an average age limit to the realisation of the assessment of thrombophilia. Not all of these patients had any causal other than hyperhomocysteinemia secondary to Biermer's disease. The support is not detailed. CONCLUSION: Hyperhomocysteinemia is probably not the only thromboembolic factor. The patient received anticoagulation and vitamin B12 supplementation. A good reading of the complete blood count is essential.

[Impact of prematurity on the optic nerve]. / Impact de la prématurité sur l'aspect morphologique et tomographique du nerf optique.

INTRODUCTION: Thanks to the progress made in the past few years in pediatric intensive care as well as the increased survival of preterm infants, the consequences of premature birth are increasingly well documented. With regard to ophthalmologic complications, retinopathy of prematurity is well described, but the optic nerve may also be affected. The goal of this study is to compare the optic nerves of preterm infants as a function of their gestational period with a control group of the same age. MATERIALS AND METHODS: We conducted a case-control study pairing a full-term infant with each preterm infant. Inclusion criteria were: any child from 5- to 10-years-old, separated into three sub-groups according to their degree of prematurity. Variables were: cup/disc ratio, ocular biometry, intraocular pressure and RNFL thickness. RESULTS: Thirty-seven preterm infants and 37 controls were included in the study. The mean age at the time of inclusion was 7.05 years for the preterm group and 7.19 years for the control group. No significant difference was observed in axial length or spherical equivalent (P=0.31 and P=0.98, respectively). No significant difference was observed in pachymetry or intraocular pressure (P=0.28 and P=0.22, respectively). We observed a significant increase of 0.1 in the cup/disc ratio of the preterm group compared to the control group (P<0.05). The preterm group cup/disc ratio was 0.36 versus 0.27 for the control group. No significant difference was observed in the 7 quadrants of RNFL between the two groups. However, when comparing infants born before 28 weeks gestation with the control group, we observed a mean decrease of 14.5 microns in the superior temporal sector (P=0.04), a 9 micron decrease in the global thickness G (P=0.03) and a 12.7 micron decrease in the nasal sector (P=0.01). CONCLUSIONS: In the case of the studied children (aged 5 to 10), the reduced RNFL fiber thickness is a phenomenon dependent essentially on the stage of prematurity. It would be useful to follow these preterm populations over the long term and to compare them to a matched control group to be able to obtain functional results.

Effects of parity, blood progesterone, and non-steroidal anti-inflammatory treatment on the dynamics of the uterine microbiota of healthy postpartum dairy cows.

This study evaluated the effects of treatment with meloxicam (a non-steroidal anti-inflammatory drug), parity, and blood progesterone concentration on the dynamics of the uterine microbiota of 16 clinically healthy postpartum dairy cows. Seven primiparous and 9 multiparous postpartum Holstein cows either received meloxicam (0.5 mg/kg SC, n = 7 cows) once daily for 4 days (10 to 13 days in milk (DIM)) or were untreated (n = 9 cows). Endometrial cytology samples were collected by cytobrush at 10, 21, and 35 DIM, from which the microbiota analysis was conducted using 16S rRNA gene sequence analysis. A radioimmunoassay was used to measure progesterone concentration in blood serum samples at 35 DIM and cows were classified as ˃ 1 ng/mL (n = 10) or ≤ 1 ng/mL (n = 6). Alpha diversity for bacterial genera (Chao1, Shannon-Weiner, and Camargo's evenness indices) were not affected by DIM, meloxicam treatment, parity, or progesterone category. For beta diversity (genera level), principal coordinate analysis (Bray-Curtis) showed differences in microbiota between parity groups. At the phylum level, the relative abundance of Actinobacteria was greater in primiparous than multiparous cows. At the genus level, there was lesser relative abundance of Bifidobacterium, Lactobacillus, Neisseriaceae, Paracoccus, Staphylococcus, and Streptococcus and greater relative abundance of Bacillus and Fusobacterium in primiparous than multiparous cows. Bray-Curtis dissimilarity did not differ by DIM at sampling, meloxicam treatment, or progesterone category at 35 DIM. In conclusion, uterine bacterial composition was not different at 10, 21, or 35 DIM, and meloxicam treatment or progesterone category did not affect the uterine microbiota in clinically healthy postpartum dairy cows. Primiparous cows presented a different composition of uterine bacteria than multiparous cows. The differences in microbiota associated with parity might be attributable to changes that occur consequent to the first calving, but this hypothesis should be investigated further.

Dynamics of uterine microbiota in postpartum dairy cows with clinical or subclinical endometritis.

Our objectives were to describe and compare the uterine bacterial composition of postpartum Holstein cows diagnosed as healthy (n = 8), subclinical endometritis (SCE; n = 8), or clinical endometritis (CE; n = 5) in the fifth week postpartum. We did metagenomic analyses of 16S rRNA gene sequences from endometrial cytobrush samples at 10, 21, and 35 days in milk (DIM), and endometrial bacterial culture at 35 DIM. Uterine bacterial composition in healthy, SCE, and CE was stable at 10, 21, and 35 DIM. Alpha and beta diversities showed a different uterine microbiome from CE compared to healthy or SCE, but no differences were found between healthy and SCE cows. At the phylum level, the relative abundance of Bacteroidetes and Fusobacteria, and at genera level, of Trueperella was greater in CE than healthy or SCE cows. Trueperella pyogenes was the predominant bacteria cultured in cows with CE, and a wide variety of bacterial growth was found in healthy and SCE cows. Bacteria that grew in culture were represented within the most abundant bacterial genera based on metagenomic sequencing. The uterine microbiota was similar between SCE and healthy, but the microbiome in cows with CE had a loss of bacterial diversity.

Prognostic value of diffusion-weighted magnetic resonance imaging of brain in fetal growth restriction: results of prospective multicenter study.

OBJECTIVE: To measure prospectively apparent diffusion coefficient (ADC) values between 28 and 32 weeks of gestation in different cerebral territories of fetuses with estimated fetal weight (EFW) ≤ 5th centile, and analyze their association with adverse perinatal outcome. METHODS: This was a prospective study involving six tertiary-level perinatal centers. In the period 22 November 2016 to 11 September 2017, we included singleton, small-for-gestational-age (SGA) fetuses with EFW ≤ 5th percentile, between 28 and 32 weeks of gestation, regardless of the umbilical artery Doppler and maternal uterine artery Doppler findings. A fetal magnetic resonance imaging (MRI) examination with diffusion-weighted sequences (DWI) was performed within 14 days following inclusion and before 32 weeks. ADC values were calculated in the frontal and occipital white matter, basal ganglia and cerebellar hemispheres. An ultrasound examination was performed within 1 week prior to the MRI examination. The primary outcome was a composite measure of adverse perinatal outcome, defined as any of the following: perinatal death; admission to neonatal intensive care unit with mechanical ventilation > 48 h; necrotizing enterocolitis; Grade III-IV intraventricular hemorrhage; periventricular leukomalacia. A univariate comparison of median ADC values in all cerebral territories between fetuses with and those without adverse perinatal outcome was performed. The association between ADC values and adverse perinatal outcome was then analyzed using multilevel logistic regression models to adjust for other common prognostic factors for growth-restricted fetuses. RESULTS: MRI was performed in 64 patients, of whom five were excluded owing to fetal movement artifacts on DWI and two were excluded for termination of pregnancy with no link to fetal growth restriction (FGR). One intrauterine death occurred secondary to severe FGR. Among the 56 liveborn neonates, delivered at a mean ± SD gestational age of 33.6 ± 3.0 weeks, with a mean birth weight of 1441 ± 566 g, four neonatal deaths occurred. In addition, two neonates required prolonged mechanical ventilation, one of whom also developed necrotizing enterocolitis. Overall, therefore, seven out of 57 (12.3%) cases had an adverse perinatal outcome (95% CI, 3.8-20.8%). The ADC values in the frontal region were significantly lower in the group with adverse perinatal outcome vs those in the group with favorable outcome (mean values of both hemispheres, 1.68 vs 1.78 × 10-3 mm2 /s; P = 0.04). No significant difference in ADC values was observed between the two groups in any other cerebral territory. A cut-off value of 1.70 × 10-3 mm2 /s was associated with a sensitivity of 57% (95% CI, 18-90%), a specificity of 78% (95% CI, 63-88%), a positive predictive value of 27% (95% CI, 8-55%) and a negative predictive value of 93% (95% CI, 80-98%) for the prediction of adverse perinatal outcome. A mean frontal ADC value < 1.70 × 10-3 mm2 /s was not associated significantly with an increased risk of adverse perinatal outcome, either in the univariate analysis (P = 0.07), or when adjusting for gestational age at MRI and fetal sex (odds ratio (OR), 6.06 (95% CI, 0.9-37.1), P = 0.051) or for umbilical artery Doppler (OR, 6.08 (95% CI, 0.89-41.44)). CONCLUSION: This first prospective, multicenter, cohort study using DWI in the setting of SGA found lower ADC values in the frontal white-matter territory in fetuses with, compared with those without, adverse perinatal outcome. To determine the prognostic value of these changes, further standardized evaluation of the neurodevelopment of children born with growth restriction is required. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Two bifunctional desferrioxamine chelators for bioorthogonal labeling of biovectors with zirconium-89.

We report two bifunctional chelators, DFO-Cys and DFO-CBT, to label biovectors with zirconium-89 according to the 2-cyanobenzothiazole/1,2-aminothiol cycloaddition. Their features are high labeling yields, rapid and efficient bioconjugation, metabolically stable luciferin-based end products, and applicability to orthogonal two-step labeling of sensitive biomolecules.

The state of knowledge on technologies and their use for fall detection: A scoping review.

BACKGROUND: Globally, populations are aging with increasing life spans. The normal aging process and the resulting disabilities increase fall risks. Falls are an important cause of injury, loss of independence and institutionalization. Technologies have been developed to detect falls and reduce their consequences but their use and impact on quality of life remain debatable. Reviews on fall detection technologies exist but are not extensive. A comprehensive literature review on the state of knowledge of fall detection technologies can inform research, practice, and user adoption. OBJECTIVES: To examine the extent and the diversity of current technologies for fall detection in older adults. METHODS: A scoping review design was used to search peer-reviewed literature on technologies to detect falls, published in English, French or Spanish since 2006. Data from the studies were analyzed descriptively. RESULTS: The literature search identified 3202 studies of which 118 were included for analysis. Ten types of technologies were identified ranging from wearable (e.g., inertial sensors) to ambient sensors (e.g., vision sensors). Their Technology Readiness Level was low (mean 4.54 SD 1.25; 95% CI [4.31, 4.77] out of a maximum of 9). Outcomes were typically evaluated on technological basis and in controlled environments. Few were evaluated in home settings or care units with older adults. Acceptability, implementation cost and barriers were seldom addressed. CONCLUSIONS: Further research should focus on increasing Technology Readiness Levels of fall detection technologies by testing them in real-life settings with older adults.

Palivizumab administration in preterm infants in France: EPIPAGE-2 cohort study.

BACKGROUND: Several countries, including France, have restricted the indications for monoclonal antibodies directed against respiratory syncytial virus (RSV) compared to the marketing authorization (MA). No new data concerning use of palivizumab on a national scale have been published since the 2007 update of the national guidelines. OBJECTIVES: To describe palivizumab administration for RSV prophylaxis during the first RSV season in infants born prematurely in France in 2011. METHODS: Infants from the national population-based cohort EPIPAGE-2 born at≤34 weeks' gestation, discharged home before 31 March 2012 and followed-up at 1year were included. The RSV season ran from 1 October 2011 to 31 March 2012. Prophylaxis was deemed "initiated" if the infant had received at least one dose of palivizumab during this period and "complete" if it had received at least five doses or as many doses as the number of exposed months. The reference documents were the MA and French Transparency Committee guidelines (TC). RESULTS: Prophylaxis was indicated in 3586 of 3608 infants (99.7%) according to the MA and 1315 of 3608 (16.7%) according to the TC. A total of 1906 infants (26.6%) received at least one dose of palivizumab. The overall rate of conformity with TC indications was 85%, but was lower for infants born at 27-32 weeks' gestation. The rate of complete prophylaxis was 77.2%. The factors associated with prophylaxis initiation were low gestational age, low birthweight, high maternal educational level, type of neonatal unit, and date at discharge. Factors associated with complete prophylaxis were respiratory impairment, high educational level, and characteristics related to living conditions (absence of siblings at home, type of childcare). CONCLUSIONS: Palivizumab administration in France generally conformed with TC guidelines, but could be further improved for infants born at 27-32 weeks' gestation without bronchopulmonary dysplasia.

Examining the epidemiology and microbiology of Clostridium difficile carriage in elderly patients and residents of a healthcare facility in southern Ontario, Canada.

BACKGROUND: Whereas Clostridium difficile has been extensively studied in acute care facilities (ACFs), there is limited information about long-term care facilities (LTCFs), despite the high occurrence of putative risk factors (e.g. age, antimicrobial use, healthcare system contact). AIM: To evaluate C. difficile colonization in elderly patients and residents from one ACF and its associated LTCF. METHODS: Stool swabs were collected from 884 LTCF and elderly (>65 years) hospital patients. Selective culture, polymerase chain reaction ribotyping and toxin gene characterization were performed. FINDINGS: C. difficile was isolated from 92/410 (22.4%) ACF and 89/474 (18.8%) LTCF samples. Ribotypes 027 (35%) and 020 (10.4%) predominated in the LTCF whereas ribotypes AI-82/1 (20.7%) and ribotype O (14.1%) predominated at the ACF (P = 0.031). In the LTCF, C. difficile colonization was associated with a history of proton pump inhibitor (PPI) use, and the interaction terms of male residents with prior medical leave of absence, and a prior history of C. difficile infection (CDI) combined with fluoroquinolone use. In the ACF, C. difficile colonization was associated with length of stay, feeding through a tube, antibiotic use, immunosuppressive therapy and VRE colonization, as well as the interaction terms for cephalosporin and fluoroquinolone use, prior CDI and cephalosporin use, and prior CDI and fluoroquinolone use. CONCLUSION: C. difficile colonization by ACF and LTCF residents was common, despite a low apparent incidence of CDI. The association with PPI provides further evidence of the potential importance of this widely used drug class in C. difficile colonization. Wide genetic diversity was present, highlighting the likelihood of multiple unidentified routes of C. difficile acquisition.

Deletion of the GAA repeats from the human frataxin gene using the CRISPR-Cas9 system in YG8R-derived cells and mouse models of Friedreich ataxia.

The Friedreich ataxia is a monogenic disease due to a hyperexpanded GAA triplet located within the first intron of the frataxin gene that causes transcriptional issues. The resulting frataxin protein deficiency leads to a Fe-S cluster biosynthesis dysfunction in the mitochondria and to oxidative stress and cell death. Here we use the CRISPR-Cas9 system to remove the mutated GAA expansion and restore the frataxin gene transcriptional activity and protein level. Both YG8R and YG8sR mouse models and cell lines derived from these mice were used to CRISPR-edited successfully the GAA expansion in vitro and in vivo. Nevertheless, our results suggest the YG8sR as a better and more suitable model for the study of the CRISPR-Cas9 edition of the mutated frataxin gene.

Evidence of a multiple insecticide resistance in the malaria vector Anopheles funestus in South West Nigeria.

BACKGROUND: Knowing the extent and spread of insecticide resistance in malaria vectors is vital to successfully manage insecticide resistance in Africa. This information in the main malaria vector, Anopheles funestus sensu stricto, is completely lacking in the most populous country in Africa, Nigeria. This study reports the insecticide susceptibility status and the molecular basis of resistance of An. funestus as well as its involvement in malaria transmission in Akaka-Remo, a farm settlement village in southwest Nigeria. RESULTS: Plasmodium infection analysis using TaqMan protocol coupled with a nested PCR revealed an infection rate of 8% in An. funestus s.s. from Akaka-Remo. WHO susceptibility tests showed this species has developed multiple resistance to insecticides in the study area. Anopheles funestus s.s. population in Akaka-Remo is highly resistant to organochlorines: dieldrin (8%) and DDT (10%). Resistance was also observed against pyrethroids: permethrin (68%) and deltamethrin (87%), and the carbamate bendiocarb (84%). Mortality rate with DDT slightly increased (from 10 to 30%, n = 45) after PBO pre-exposure indicating that cytochrome P450s play little role in DDT resistance while high mortalities were recorded after PBO pre-exposure with permethrin (from 68 to 100%, n = 70) and dieldrin (from 8 to 100%, n = 48) suggesting the implication of P450s in the observed permethrin and dieldrin resistance. High frequencies of resistant allele, 119F in F0 (77%) and F1 (80% in resistant and 72% in susceptible) populations with an odd ratio of 1.56 (P = 0.1859) show that L119F-GSTe2 mutation is almost fixed in the population. Genotyping of the A296S-RDL mutation in both F0 and F1 samples shows an association with dieldrin resistance with an odd ratio of 81 (P < 0.0001) (allelic frequency (R) = 76% for F0; for F1, 90 and 10% were observed in resistant and susceptible populations, respectively) as this mutation is not yet fixed in the population. CONCLUSION: The study reports multiple insecticide resistance in An. funestus from Akaka Remo. It is, therefore, necessary to pay more attention to this major malaria vector for effective malaria control in Nigeria.

Development of an AAV9 coding for a 3XFLAG-TALEfrat#8-VP64 able to increase in vivo the human frataxin in YG8R mice.

Artificially designed transcription activator-like effector (TALE) proteins fused to a transcription activation domain (TAD), such as VP64, are able to activate specific eukaryotic promoters. They thus provide a good tool for targeted gene regulation as a therapy. However, the efficacy of such an agent in vivo remains to be demonstrated as the majority of studies have been carried out in cell culture. We produced an adeno-associated virus 9 (AAV9) coding for a TALEfrat#8 containing 13 repeat variable diresidues able to bind to the proximal promoter of human frataxin (FXN) gene. This TALEfrat#8 was fused with a 3XFLAG at its N terminal and a VP64 TAD at its C terminal, and driven by a CAG promoter. This AAV9_3XFLAG-TALEfrat#8-VP64 was injected intraperitoneally to 9-day-old and 4-month-old YG8R mice. After 1 month, the heart, muscle and liver were removed and their FXN mRNA and FXN protein were analyzed. The results show that the AAV9_3XFLAG-TALEfrat#8-VP64 increased the FXN mRNA and FXN protein in the three organs studied. These results corroborate our previous in vitro studies in the FRDA human fibroblasts. Our study indicates that an AAV coding for a TALE protein coupled with a TAD may be used to increase gene expression in vivo as a possible treatment not only for FRDA but also for other haploinsufficiency diseases.

Serum periostin is associated with prevalent knee osteoarthritis and disease incidence/progression in women: the OFELY study.

OBJECTIVE: Our aim was to investigate the relationships between serum periostin (POSTN) and both prevalence and incidence/progression of knee osteoarthritis (OA) in women. METHODS: We investigated 594 women (62.7 ± 11.2 yr) from the OFELY cohort. Knee radiographs were scored according to the Kellgren & Lawrence (KL) grading system at baseline and 4 years later. Spine, hip and hand OA were assessed at baseline. Prevalent knee OA was defined by a KL score higher or equal in 2. Progression of KL was defined as an increase of the KL score ≥1 during the 4 years follow-up. Serum POSTN was measured at baseline by ELISA. RESULTS: By non-parametric tests, POSTN was significantly lower in 83 women with a KL score ≥2 at baseline, compared to those with a KL score <2 (n = 511; 1101 ± 300 vs 1181 ± 294 ng/ml, P = 0.002) after adjustment for age, body mass index (BMI), treatments and diseases, prevalent hand OA and prevalent lumbar spine OA. By logistic regression analyses, the odds-ratio of knee OA incidence/progression was significantly reduced by 21% (P = 0.043) for each quartile increase in serum POSTN at baseline, after adjustment for age, BMI, prevalent knee OA, prevalent hand OA and prevalent lumbar spine OA. CONCLUSIONS: We show for the first time that serum POSTN is associated with prevalence and the risk of development/progression of knee OA in women.

The effects of sex and neonatal stress on pituitary adenylate cyclase-activating peptide expression.

NEW FINDINGS: What is the central question of this study? Does sex or neonatal stress affect the expression of pituitary adenylate cyclase-activating peptide or its receptors? What is the main finding and its importance? Neonatal-maternal separation stress has little long-lasting effect on the expression of pituitary adenylate cyclase-activating peptide or its receptors, but sex differences exist in these genes between males and females at baseline. Sex differences in classic stress hormones have been studied in depth, but pituitary adenylate cyclase-activating peptide (PACAP), recently identified as playing a critical role in the stress axes, has not. Here we studied whether baseline levels of PACAP differ between sexes in various stress-related tissues and whether neonatal-maternal separation stress has a sex-dependent effect on PACAP gene expression in stress pathways. Using quantitative RT-PCR, we found sex differences in PACAP and PACAP receptor gene expression in several respiratory and/or stress-related tissues, while neonatal-maternal separation stress did little to affect PACAP signalling in adult animals. We propose that sex differences in PACAP expression are likely to contribute to differences between males and females in responses to stress.

Serum periostin is associated with fracture risk in postmenopausal women: a 7-year prospective analysis of the OFELY study.

PURPOSE: Periostin (POSTN) is a secreted γ-carboxyglutamic acid-containing protein expressed mainly in the periosteum in adult individuals. POSNT deficient mice develop periodontis and osteoporosis with decreased bone strength. The relationship between serum POSTN and bone metabolism and fracture risk in postmenopausal women is unknown. SUBJECTS AND METHODS: Serum POSTN was measured in 607 postmenopausal women (mean age 66.6 ± 8.4 y) from the Os des Femmes de Lyon cohort at the ninth annual follow-up visit (baseline visit of the current analysis). Nonvertebral and clinical vertebral incident fragility fractures were reported annually during 7 years. Areal bone mineral density (BMD; measured by dual energy X-ray absorptiometry) of the hip and bone markers (intact N-terminal propeptide of type I collagen, osteocalcin, and serum type I collagen C-telopeptide) were also measured. RESULTS: At baseline, serum POSTN did not correlate with age, bone markers, and BMD. After a median of 7 years of follow-up, 75 women sustained an incident clinical vertebral or nonvertebral fragility fracture. The proportion of women who had an incident fracture was significantly higher in women with levels of POSTN in the highest quartile than that of women in the three other quartiles (19.5% vs 10.1%, P = .018) after adjustment for age and prevalent fracture. The highest quartile of POSTN was associated with an increased risk of incident fracture with a relative risk (95% confidence interval) of 1.88 (1.1-3.2) after adjustment for age, prevalent fracture, and hip BMD T-score. Patients with both low hip BMD (T-score < -2.5) and high levels of POSTN (fourth quartile) had a relative risk of fracture of 7.1 (95% confidence interval 2.4-21.8) after adjustment for age. CONCLUSION: High serum POSTN levels are independently associated with increased fracture risk in postmenopausal women. These data suggest that serum POSTN could be useful to improve fracture risk assessment.

The association of cytochrome P450 genetic polymorphisms with sulfolane formation and the efficacy of a busulfan-based conditioning regimen in pediatric patients undergoing hematopoietic stem cell transplantation.

Cytochrome P450 enzymes (CYPs) and flavin-containing monooxygenases (FMOs) likely have a role in the oxidation of intermediate metabolites of busulfan (Bu). In vitro studies to investigate the involvement of these enzymes are cumbersome because of the volatile nature of the intermediate metabolite tetrahydrothiophene (THT) and the lack of sensitive quantitation methods. This study explored the association between the CYP2C9, CYP2C19, CYP2B6 and FMO3 genotypes and sulfolane (Su, a water soluble metabolite of Bu) plasma levels in children undergoing hematopoietic stem cell transplantation (HSCT). The relationship between these genotypes and the effectiveness of myeloablative conditioning was also analyzed. Sixty-six children receiving an intravenous Bu-based myeloablative conditioning regimen were genotyped for common functional variant alleles in CYP2C9 (*2 and *3), CYP2C19 (*2 and *17), FMO3 (rs2266780, rs2266782 and rs1736557) and CYP2B6 (*5 and *9). The plasma levels of Bu and its metabolite Su were measured after the ninth Bu dose in a subset of 44 patients for whom plasma samples were available. The ratio of Bu to Su was considered the metabolic ratio (MR) and was compared across the genotype groups. Higher MRs were observed in CYP2C9*2 and *3 allele carriers (mean±s.d.: 7.8±3.6 in carriers vs 4.4±2.2 in non-carriers; P=0.003). An increased incidence of graft failure was observed among patients with an MR>5 compared with those with MR values <5 (20% vs 0%; P=0.02). In contrast, a significantly higher incidence of relapse and graft failure (evaluated as event-free survival) was observed in patients with malignant disease who carried CYP2B6 alleles with reduced function on both chromosomes compared with carriers of at least one normal allele (100% vs 40%; P=0.0001). These results suggest that CYP2C9 has a role in the oxidation reactions of THT and indicate that it may be possible to predict the efficacy of Bu-based myeloablative conditioning before HSCT on the basis of CYP genotypes and Bu MRs.

Invisible bleeding from clean-shave haircuts: detection with blood specific RNA markers.

BACKGROUND: 'Haircut-associated bleeding' is a newly recognized entity that affects at least a quarter of African men who wear shiny clean-shave ('chiskop') haircuts. AIM: This pilot study aimed to elucidate whether invisible haircut-associated bleeding was detectable using blood specific RNA markers (16 participants, 5 with unknown HIV status) and whether surface virus could be detected using PCR from scalp swabs (of 11 known HIV-positive participants). METHODS: Haircuts were performed professionally and scalps examined by a dermatologist to exclude injury. Serum samples for viral loads were also collected at the same time. RESULTS: In all, 6/16 (37%) samples tested positive (>100 relative fluorescent units) for hemoglobin beta and albumin, confirming evidence of blood; of these, only 1/11 was HIV-positive but had an undetectable serum viral load. No surface HIV was detected from any scalp samples. CONCLUSIONS: This study confirms the entity of haircut-associated bleeding but goes further to show for the first time that invisible bleeding from clean-shave haircuts is also common. Both a high serum viral load and evidence of bleeding should ideally be present prior to surface HIV detection. Future investigations for potential HIV (and hepatitis B) transmission through clean-shave haircuts are warranted but should not delay public education for disease prevention.