Preparation and characterization of a three-dimensional printed scaffold based on a functionalized polyester for bone tissue engineering applications

At present there is a strong need for suitable scaffolds that meet the requirements for bone tissue engineering applications. The objective of this study was to investigate the suitability of porous scaffolds based on a hydroxyl functionalized polymer, poly(hydroxymethylglycolide-co-ε-caprolactone) (pHMGCL), for tissue engineering. In a recent study this polymer was shown to be a promising material for bone regeneration. The scaffolds consisting of pHMGCL or poly(ε-caprolactone) (PCL) were produced by means of a rapid prototyping technique (three-dimensional plotting) and were shown to have a high porosity and an interconnected pore structure. The thermal and mechanical properties of both scaffolds were investigated and human mesenchymal stem cells were seeded onto the scaffolds to evaluate the cell attachment properties, as well as cell viability and differentiation. It was shown that the cells filled the pores of the pHMGCL scaffold within 7 days and displayed increased metabolic activity when compared with cells cultured in PCL scaffolds. Importantly, pHMGCL scaffolds supported osteogenic differentiation. Therefore, scaffolds based on pHMGCL are promising templates for bone tissue engineering applications.     

Prevalence and characteristics of heteroresistant vancomycin-intermediate Staphylococcus aureus bacteremia in a tertiary care center

Infections with S. aureus with heterogeneous intermediate resistance to vancomycin (hVISA) are occurring more frequently. The detection of these infections, their prevalence, clinical characteristics, and significance are controversial. During 2003 and 2004, all blood culture isolates of methicillin-resistant Staphylococcus aureus (264 patients) at the Sheba Medical Center, Tel Hashomer, Israel, were assessed for hVISA by using the Etest macromethod. A total of 16 patients (6%) were positive for hVISA. Resistance to teicoplanin alone and to vancomycin alone using the Etest macromethod was found in 14 and 10 patients, respectively. Standard MICs to vancomycin were between 1 to 4 mg/ml. Most of these isolates (12 of 16 [75%]) would have been missed without specific testing. The median number of bacteremic days was 4. Seven patients had positive blood cultures for more than 5 days. Twelve patients died, and for eight of these the deaths were directly related to hVISA sepsis. We found that hVISA bacteremia was prevalent in our institution, and we suggest seeking hVISA in patients with persistent S. aureus bacteremia.     

Pubic Hair Removal and Sexual Behavior: Findings from a Prospective Daily Diary Study of Sexually Active Women in the United States

IntroductionPubic hair removal is prevalent among women in the United States. However, most studies related to pubic hair removal are based on cross‐sectional surveys and retrospective recall.AimThe purpose of this research was to, in a prospective event‐level daily diary study, assess demographic, affective, relational, situational, and behavioral factors related to women's pubic hair removal.MethodData collection occurred as part of a 5‐week prospective, Internet‐based daily diary study.Main Outcome MeasuresAge; Affective predictors (positive mood, negative mood, feeling interested in sex, feeling in love); Relational predictors (partner support, partner negativity, partner type, partner gender); Situational predictors (any vaginal symptoms, use of any vaginal hygiene products; having applied any creams to the genitals); Behavioral variables (penile–vaginal sex, penile–anal sex, had finger inserted into vagina, had clitoris stimulated with fingers, inserted toy into vagina, used vibrator on clitoris, inserted finger into anus, inserted toy into anus, duration of penetration, intensity of penetration).ResultsA total of 2,453 women ages 18 to 68 (mean age 32.69) completed the study, contributing 49,287 total diaries (mean per person 24.5; standard deviation 10.3, median 30); 15.2% of all days (N = 7,362) involved pubic hair waxing or shaving, with the vast majority of hair removal days involving shaving (N = 7,302; 99%). Pubic hair removal was significantly associated with younger age, a greater interest in sex, vaginal fingering, finger–clitoral stimulation, having a casual sex partner, using vaginal hygiene products, and applying cream to the genitals. Hair removal was marginally associated with longer duration of vaginal penetration.ConclusionsThese findings provide greater insight into the factors associated with women's pubic hair removal and their sexual experiences on a day‐to‐day level. Clinical and educational implications are discussed. Herbenick D, Hensel D, Smith NK, Schick V, Reece M, Sanders SA, and Fortenberry JD. Pubic hair removal and sexual behavior: Findings from a prospective daily diary study of sexually active women in the United States. J Sex Med 2013;10:678–685.     

Characteristics of Condom and Lubricant Use among a Nationally Representative Probability Sample of Adults Ages 18–59 in the United States

IntroductionAlthough most Americans have used condoms and/or lubricant during sex, little is known about the context of sexual events that involve the use of such products outside of experimentally manipulated studies.AimsTo assess, in a nationally representative study of men and women in the United States ages 18–59, the characteristics of condom and lubricant use during participants' most recent sexual event and the relationship of their condom and lubricant use to event‐level ratings of sexual quality.MethodsData are from the National Survey of Sexual Health and Behavior, which involved the administration of an online questionnaire to a nationally representative probability sample of the U.S. adults.Main Outcome MeasuresSociodemographic items: event‐level items related to sexual behavior, condom use, lubricant use, and participants' perceptions of their arousal, pleasure, ease of erection or lubrication, and pain associated with sex.ResultsDuring their most recent sexual experience, 27.5% of men (N = 237) and 22.3% of women (N = 175) reported using a condom. More than twice as many women as men were unsure whether the condom was lubricated (26.6% vs. 11.4%) and the material it was made of (23.6% vs. 8.9%). Participants consistently rated sex to be arousing and pleasurable whether or not they used condoms or lubricant. No significant differences were found in regard to men's ratings of the ease of their erections based on condom and lubricant use.ConclusionsAlthough some have concerns about how condoms or lubricants may impact their enjoyment of sex, in a nationally representative sample of men and women ages 18–59, ratings of sex were largely quite high, with few differences based on condom and lubricant use. Women, more often than men, reported being unsure about the type of condom and lubricant used, which has implications for patient education. Herbenick D, Schick V, Reece M, Sanders SA, Smith N, Dodge B, and Fortenberry JD. Characteristics of condom and lubricant use among a nationally representative probability sample of adults ages 18–59 in the United States. J Sex Med **;**:**–**.     

Inhibiting activin‐A signaling stimulates bone formation and prevents cancer‐induced bone destruction in vivo

Cancers that grow in bone, such as myeloma and breast cancer metastases, cause devastating osteolytic bone destruction. These cancers hijack bone remodeling by stimulating osteoclastic bone resorption and suppressing bone formation. Currently, treatment is targeted primarily at blocking bone resorption, but this approach has achieved only limited success. Stimulating osteoblastic bone formation to promote repair is a novel alternative approach. We show that a soluble activin receptor type IIA fusion protein (ActRIIA.muFc) stimulates osteoblastogenesis (p < .01), promotes bone formation (p < .01) and increases bone mass in vivo (p < .001). We show that the development of osteolytic bone lesions in mice bearing murine myeloma cells is caused by both increased resorption (p < .05) and suppression of bone formation (p < .01). ActRIIA.muFc treatment stimulates osteoblastogenesis (p < .01), prevents myeloma‐induced suppression of bone formation (p < .05), blocks the development of osteolytic bone lesions (p < .05), and increases survival (p < .05). We also show, in a murine model of breast cancer bone metastasis, that ActRIIA.muFc again prevents bone destruction (p < .001) and inhibits bone metastases (p < .05). These findings show that stimulating osteoblastic bone formation with ActRIIA.muFc blocks the formation of osteolytic bone lesions and bone metastases in models of myeloma and breast cancer and paves the way for new approaches to treating this debilitating aspect of cancer. © 2010 American Society for Bone and Mineral Research.     

Altered circadian locomotor activity in APP23 mice: a model for BPSD disturbances

Over the past decade, clinical Alzheimer's disease research has been challenged with an increased interest in noncognitive symptomatology, commonly referred to as behavioural and psychological signs and symptoms of dementia (BPSD). In accordance, major attention is being paid to behavioural alterations in the phenotyping of transgenic mouse models. Besides an age-dependent decline of cognitive functions, the APP23 model was previously shown to exhibit cage activity disturbances, reminiscent of diurnal rhythm disturbances in Alzheimer patients. To further scrutinize these observations, circadian patterns of horizontal locomotor activity were assessed in 3-, 6- and 12-month-old APP23 mice and wild-type littermates in a test paradigm continuously recording cage activity over a period ranging from 1 to 3 days. At the age of 3 months, APP23 profiles resembled the wild-type pattern to a large extent, although minor differences were already noticeable. Six-month-old APP23 mice displayed an altered activity profile with a first indication of increased activity during the second half of the active phase, reminiscent of sundowning behaviour in Alzheimer patients. This bimodal overnight activity pattern became even more evident at the age of 12 months. The APP23 model was therefore shown to display an age-dependent development of cage activity disturbances and sundowning-like behaviour. A comparison is made with actigraphic recordings of human Alzheimer patients exhibiting sundowning behaviour. This first report of diurnal rhythm disturbances and sundowning-like phenomena in a transgenic mouse model greatly adds to the validity of the APP23 model.     

Genetic counseling for psychiatric disorders

Like other medical conditions, some psychiatric disorders are inherited, whereas others are not. Human genetics research is moving at a rapid pace. Genes for over 450 genetic disorders have been cloned and many disease-causing mutations have also been identified. The explosion of this new knowledge has created many new exciting opportunities in the diagnosis of these heritable disorders. The rapid pace of gene discovery will aid the identification of susceptibility genes for psychiatric disorders. Indeed, we can look forward to answers to many clinical and research questions. These are some of the gifts that the expanding field of human genetics research will continue to bring to medical science. However, as genetic tests for the detection of psychiatric disorders become available, many ethical, legal, and social implications will need to be considered. In this article, we review the principles of genetic counseling for psychiatric disorders, as well as the social and ethical dilemmas that genetic testing may bring. Although medical and scientific advances may bring many gifts, we should approach this new knowledge with caution, as one of the gifts may be a Pandora’s box.     

Comparison of the Heritability of Schizophrenia and Endophenotypes in the COGS-1 Family Study

Background:

Twin and multiplex family studies have established significant heritability for schizophrenia (SZ), often summarized as 81%. The Consortium on the Genetics of Schizophrenia (COGS-1) family study was designed to deconstruct the genetic architecture of SZ using neurocognitive and neurophysiological endophenotypes, for which heritability estimates ranged from 18% to 50% (mean = 30%). This study assessed the heritability of SZ in these families to determine whether there is a “heritability gap” between the diagnosis and related endophenotypes.

Methods:

Nuclear families (N = 296) with a SZ proband, an unaffected sibling, and both parents (n = 1366 subjects; mean family size = 4.6) underwent comprehensive endophenotype and clinical characterization. The Family Interview for Genetic Studies was administered to all participants and used to obtain convergent psychiatric symptom information for additional first-degree relatives of interviewed subjects (N = 3304 subjects; mean family size = 11.2). Heritability estimates of psychotic disorders were computed for both nuclear and extended families.

Results:

The heritability of SZ was 31% and 44% for nuclear and extended families. The inclusion of bipolar disorder increased the heritability to 37% for the nuclear families. When major depression was added, heritability estimates dropped to 34% and 20% for nuclear and extended families, respectively.

Conclusions:

Endophenotypes and psychotic disorders exhibit comparable levels of heritability in the COGS-1 family sample. The ascertainment of families with discordant sibpairs to increase endophenotypic contrast may underestimate diagnostic heritability relative to other studies. However, population-based studies also report significantly lower heritability estimates for SZ. Collectively, these findings support the importance of endophenotype-based strategies and the dimensional view of psychosis.Key words: schizophrenia, psychosis, endophenotypes, cognition, biomarkers, heritability     

A multidisciplinary approach unravels early and persistent effects of X-ray exposure at the onset of prenatal neurogenesis

Background

In humans, in utero exposure to ionising radiation results in an increased prevalence of neurological aberrations, such as small head size, mental retardation and decreased IQ levels. Yet, the association between early damaging events and long-term neuronal anomalies remains largely elusive.

Methods

Mice were exposed to different X-ray doses, ranging between 0.0 and 1.0 Gy, at embryonic days (E) 10, 11 or 12 and subjected to behavioural tests at 12 weeks of age. Underlying mechanisms of irradiation at E11 were further unravelled using magnetic resonance imaging (MRI) and spectroscopy, diffusion tensor imaging, gene expression profiling, histology and immunohistochemistry.

Results

Irradiation at the onset of neurogenesis elicited behavioural changes in young adult mice, dependent on the timing of exposure. As locomotor behaviour and hippocampal-dependent spatial learning and memory were most particularly affected after irradiation at E11 with 1.0 Gy, this condition was used for further mechanistic analyses, focusing on the cerebral cortex and hippocampus. A classical p53-mediated apoptotic response was found shortly after exposure. Strikingly, in the neocortex, the majority of apoptotic and microglial cells were residing in the outer layer at 24 h after irradiation, suggesting cell death occurrence in differentiating neurons rather than proliferating cells. Furthermore, total brain volume, cortical thickness and ventricle size were decreased in the irradiated embryos. At 40 weeks of age, MRI showed that the ventricles were enlarged whereas N-acetyl aspartate concentrations and functional anisotropy were reduced in the cortex of the irradiated animals, indicating a decrease in neuronal cell number and persistent neuroinflammation. Finally, in the hippocampus, we revealed a reduction in general neurogenic proliferation and in the amount of Sox2-positive precursors after radiation exposure, although only at a juvenile age.

Conclusions

Our findings provide evidence for a radiation-induced disruption of mouse brain development, resulting in behavioural differences. We propose that alterations in cortical morphology and juvenile hippocampal neurogenesis might both contribute to the observed aberrant behaviour. Furthermore, our results challenge the generally assumed view of a higher radiosensitivity in dividing cells. Overall, this study offers new insights into irradiation-dependent effects in the embryonic brain, of relevance for the neurodevelopmental and radiobiological field.

Electronic supplementary material

The online version of this article (doi:10.1186/1866-1955-7-3) contains supplementary material, which is available to authorized users.