"Psychiatric emergency consultations of minors: a qualitative study of professionals' experiences".

BACKGROUND: Psychiatric emergency assessment of minors can be a complex process, especially for professional staff who are not specifically trained in handling child and adolescent emergency patients. As minors cannot usually express their feelings and experiences as well as adults, it is difficult to form an accurate picture of their condition and to determine what kind of emergency care is needed, for instance whether or not a psychiatric emergency admission is necessary. We lack insight in what professionals at emergency departments need to adequately assess these minors and their families. The aim of this study was to explore staff members' experiences with assessing minors and explore recommendations for improving their ability to provide appropriate support. METHODS: Guided by a topic list with open-ended questions, we conducted 11 semi-structured interviews with staff working at psychiatric emergency services. Thematic analysis enabled us to identify five main themes: (1) young age and the crucial role of parents; (2) professionals' feelings, especially uncertainty; (3) psychiatric emergency admissions and the alternatives to them; (4) regional differences in organization and tasks; and (5) options for improving care. RESULTS: The staff interviewed all agreed that it was often complicated and time consuming to take full responsibility when assessing minors with serious and urgent psychiatric problems. Most found it difficult to determine which behaviors were and were not age-appropriate, and how to handle systemic problems during the assessment. When assessing minors and their families in crisis, this led to uncertainty. Professionals were especially insecure when assessing children under age 12 and their families, feeling they lacked the appropriate knowledge and routine. CONCLUSION: Customized expertise development and improved regional embedding of the psychiatric emergency service in the child and adolescent services will reduce professionals' uncertainty and improve psychiatric emergency care for minors.

Non-visualisation of fetal gallbladder in a Chinese cohort.

INTRODUCTION: Non-visualisation of fetal gallbladder (NVFGB) is associated with chromosomal abnormalities, biliary atresia, cystic fibrosis, and gallbladder agenesis in Caucasian fetuses. We investigated the outcomes of fetuses with NVFGB in a Chinese cohort. METHODS: This retrospective analysis included cases of NVFGB among Chinese pregnant women at five public fetal medicine clinics in Hong Kong from 2012 to 2019. We compared the incidences of subsequent gallbladder visualisation, chromosomal abnormalities, biliary atresia, cystic fibrosis, and gallbladder agenesis between cases of isolated NVFGB and cases of non-isolated NVFGB. RESULTS: Among 19 cases of NVFGB detected at a median gestational age of 21.3 weeks (interquartile range, 20.0-22.3 weeks), 10 (52.6%) were isolated and nine (47.4%) were non-isolated. Eleven (58.0%) cases had transient non-visualisation, four (21.0%) had gallbladder agenesis, three (15.8%) had chromosomal abnormalities (trisomy 18, trisomy 21, and 22q11.2 microduplication), one (5.2%) had biliary atresia, and none had cystic fibrosis. The incidence of serious conditions was significantly higher in the non-isolated group than in the isolated group (44.4% vs 0%; P=0.029); all three cases with chromosomal abnormalities and the only case of biliary atresia were in the non-isolated group, while all four cases with gallbladder agenesis were in the isolated group. The incidences of transient non-visualisation were similar (55.6% vs 60.0%; P=1.000). CONCLUSION: Isolated NVFGB is often transient or related to gallbladder agenesis. While investigations for chromosomal abnormalities and biliary atresia are reasonable in cases of NVFGB, testing for cystic fibrosis may be unnecessary in Chinese fetuses unless the NVFGB is associated with consistent ultrasound features, significant family history, or consanguinity.

Relationship between viral load, infection-to-delivery interval and mother-to-child transfer of anti-SARS-CoV-2 antibodies.

OBJECTIVE: To investigate the association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and infection-to-delivery interval with maternal and cord serum concentrations of anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies and transplacental transfer ratio in pregnant women with active or recovered SARS-CoV-2 infection. METHODS: This was a prospective case series of consecutive pregnant women with laboratory-confirmed SARS-CoV-2 infection between 27 March 2020 and 24 January 2021. We collected information regarding deep throat saliva or nasopharyngeal swab (NPS) reverse transcription polymerase chain reaction (RT-PCR) test results, serial cycle threshold (Ct) values at and after diagnosis, demographic, clinical and outcome data, and neonatal NPS RT-PCR results. Qualitative and quantitative analysis of IgG and immunoglobulin M (IgM) antibodies against SARS-CoV-2 was performed in maternal and cord blood serum samples obtained at delivery. Correlation of maternal Ct values, infection-to-delivery interval, infection duration and viral load area under the curve (AUC) with gestational age (GA) at diagnosis, maternal and cord serum IgG concentrations and transplacental transfer ratio of IgG were evaluated using Pearson's correlation. RESULTS: Twenty pregnant women who consented to participate and who had delivered their babies by 31 January 2021 were included in the study, comprising 14 who had recovered from coronavirus disease 2019 (COVID-19) and six with active infection at delivery. The median GA at clinical manifestation was 32.7 (range, 11.9-39.4) weeks. The median infection-to-delivery interval and infection duration were 41.5 (range, 2-187) days and 10.0 (range, 1-48) days, respectively. The median GA at delivery was 39.1 (range, 32.4-40.7) weeks and the median seroconversion interval was 14 (range, 1-19) days. Of 13 neonates born to seropositive mothers with recovered infection at delivery, 12 tested positive for anti-SARS-CoV-2 IgG. All neonatal NPS samples were negative for SARS-CoV-2 and all cord sera tested negative for IgM. The median transplacental transfer ratio of IgG was 1.3 (interquartile range, 0.9-1.6). There was a negative correlation between infection-to-delivery interval and anti-SARS-CoV-2 IgG concentrations in maternal (r = -0.6693, P = 0.0087) and cord (r = -0.6554, P = 0.0068) serum and a positive correlation between IgG concentration in maternal serum and viral load AUC (r = 0.5109, P = 0.0310). A negative correlation was observed between transfer ratio and viral load AUC (r = -0.4757, P = 0.0409). CONCLUSIONS: In pregnant women who have recovered from COVID-19, anti-SARS-CoV-2 IgG concentrations at delivery increased with increasing viral load during infection and decreased with increasing infection-to-delivery interval. The median transplacental transfer ratio of IgG was 1.3 and it decreased with increasing viral load during infection. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Pattern and predictors of medical care received by hepatitis B carriers during pregnancy and after delivery.

OBJECTIVE: The objective of the study is to evaluate the pattern and predictors of medical care received by hepatitis B virus (HBV) carriers during pregnancy and after delivery in Hong Kong. STUDY DESIGN: The study is a retrospective analysis. METHODS: Pregnant HBV carriers and their infants were followed up for 9-12 months after delivery. Face-to-face interviews were conducted to investigate what medical care they received for HBV before, during and after pregnancy. RESULTS: Data were available for 412 HBV carriers. A total of 375 (91.0%) women were known HBV carriers before pregnancy. Routine antenatal screening picked out the remaining 37 (9.0%) HBV carriers; these women were younger, more likely to be smokers and had a lower level of education (P < 0.05) than known HBV carriers. In total, 356 of 412 (86.4%) HBV carriers did not receive any medical care for HBV during pregnancy. Known HBV carrier status, history of medical check-up and the use of antiviral treatment before pregnancy were significant predictors for HBV medical care during pregnancy (P < 0.05). The results show that 217 of 412 (52.6%) HBV carriers did not receive medical care for HBV after delivery. HBV medical care before pregnancy, use of antiviral treatment before pregnancy and a higher level of education were significant predictors for postpartum HBV medical care (P < 0.05). Multivariate analysis showed that HBV medical care before pregnancy (odds ratio [OR], 7.73; 95% confidence interval [CI], 3.21-18.65; P < 0.001) and the use of antiviral treatment (OR, 5.02; 95% CI, 1.41-17.81; P = 0.013) were associated with medical care during pregnancy. Medical care before pregnancy was also associated with postpartum HBV medical care (OR, 5.05; 95% CI, 3.29-7.51; P < 0.001). CONCLUSIONS: A significant proportion of HBV carriers did not receive HBV-related medical check-ups during and after pregnancy in Hong Kong despite the majority being aware of their carrier status. Medical care before pregnancy predicted antenatal and postpartum HBV medical care.

The first pilot study of expanded newborn screening for inborn errors of metabolism and survey of related knowledge and opinions of health care professionals in Hong Kong.

INTRODUCTION: Newborn screening is important for early diagnosis and effective treatment of inborn errors of metabolism (IEM). In response to a 2008 coroners' report of a 14-year-old boy who died of an undiagnosed IEM, the OPathPaed service model was proposed. In the present study, we investigated the feasibility of the OPathPaed model for delivering expanded newborn screening in Hong Kong. In addition, health care professionals were surveyed on their knowledge and opinions of newborn screening for IEM. METHODS: The present prospective study involving three regional hospitals was conducted in phases, from 1 October 2012 to 31 August 2014. The 10 steps of the OPathPaed model were evaluated: parental education, consent, sampling, sample dispatch, dried blood spot preparation and testing, reporting, recall and counselling, confirmation test, treatment and monitoring, and cost-benefit analysis. A fully automated online extraction system for dried blood spot analysis was also evaluated. A questionnaire was distributed to 430 health care professionals by convenience sampling. RESULTS: In total, 2440 neonates were recruited for newborn screening; no true-positive cases were found. Completed questionnaires were received from 210 respondents. Health care professionals supported implementation of an expanded newborn screening for IEM. In addition, there is a substantial need of more education for health care professionals. The majority of respondents supported implementing the expanded newborn screening for IEM immediately or within 3 years. CONCLUSION: The feasibility of OPathPaed model has been confirmed. It is significant and timely that when this pilot study was completed, a government-led initiative to study the feasibility of newborn screening for IEM in the public health care system on a larger scale was announced in the Hong Kong Special Administrative Region Chief Executive Policy Address of 2015.

High resolution MR anatomy of the subthalamic nucleus: imaging at 9.4 T with histological validation.

Using conventional MRI the subthalamic nucleus (STN) is not clearly defined. Our objective was to define the anatomy of the STN using 9.4 T MRI of post mortem tissue with histological validation. Spin-echo (SE) and 3D gradient-echo (GE) images were obtained at 9.4 T in 8 post mortem tissue blocks and compared directly with corresponding histological slides prepared with Luxol Fast Blue/Cresyl Violet (LFB/CV) in 4 cases and Perl stain in 3. The variability of the STN anatomy was studied using internal reference points. The anatomy of the STN and surrounding structures was demonstrated in all three anatomical planes using 9.4 T MR images in concordance with LFB/CV stained histological sections. Signal hypointensity was seen in 6/8 cases in the anterior and medial STN that corresponded with regions of more intense Perl staining. There was significant variability in the volume, shape and location of the borders of the STN. Using 9.4 T MRI, the internal signal characteristics and borders of the STN are clearly defined and significant anatomical variability is apparent. Direct visualisation of the STN is possible using high field MRI and this is particularly relevant, given its anatomical variability, for planning deep brain stimulation.

Intraoral Microbial Metabolism and Association with Host Taste Perception.

Metabolomics has been identified as a means of functionally assessing the net biological activity of a particular microbial community. Considering the oral microbiome, such an approach remains largely underused. While the current knowledge of the oral microbiome is constantly expanding, there are several deficits in knowledge particularly relating to their interactions with their host. This work uses nuclear magnetic resonance spectroscopy to investigate metabolic differences between oral microbial metabolism of endogenous (i.e., salivary protein) and exogenous (i.e., dietary carbohydrates) substrates. It also investigated whether microbial generation of different metabolites may be associated with host taste perception. This work found that in the absence of exogenous substrate, oral bacteria readily catabolize salivary protein and generate metabolic profiles similar to those seen in vivo. Important metabolites such as acetate, butyrate, and propionate are generated at relatively high concentrations. Higher concentrations of metabolites were generated by tongue biofilm compared to planktonic salivary bacteria. Thus, as has been postulated, metabolite production in proximity to taste receptors could reach relatively high concentrations. In the presence of 0.25 M exogenous sucrose, increased catabolism was observed with increased concentrations of a range of metabolites relating to glycolysis (lactate, pyruvate, succinate). Additional pyruvate-derived molecules such as acetoin and alanine were also increased. Furthermore, there was evidence that individual taste sensitivity to sucrose was related to differences in the metabolic fate of sucrose in the mouth. High-sensitivity perceivers appeared more inclined toward continual citric acid cycle activity postsucrose, whereas low-sensitivity perceivers had a more efficient conversion of pyruvate to lactate. This work collectively indicates that the oral microbiome exists in a complex balance with the host, with fluctuating metabolic activity depending on nutrient availability. There is preliminary evidence of an association between host behavior (sweet taste perception) and oral catabolism of sugar.

Total optical transmission through a small hole in a metal waveguide screen.

We present the theory of total optical transmission through a small hole in metal waveguide screen. Unlike past works on extraordinary optical transmission using arrays, there is only a single hole; yet, the theory predicts total transmission for a perfect electric conductor (not normalized to the hole size) 100% transmission, regardless of how small the hole. This is very surprising considering the usual application of Bethe's theory to waveguide apertures. Comprehensive numerical simulations agree well with the theory and their modal-analysis supports the proposed evanescent-mode mechanism for total transmission. These simulations are extended to show the influence of realistic material response (including loss) at microwave and visible-infrared frequencies. Due to the strong resonant field localization and transmission from only a thin metal screen with a single hole, many promising applications arise for this phenomenon including filtering, sensing, plasma generation, nonlinear optics, spectroscopy, heating, optical trapping, near-field microscopy and cavity quantum electrodynamics.

Exact results for the Kuramoto model with a bimodal frequency distribution.

We analyze a large system of globally coupled phase oscillators whose natural frequencies are bimodally distributed. The dynamics of this system has been the subject of long-standing interest. In 1984 Kuramoto proposed several conjectures about its behavior; ten years later, Crawford obtained the first analytical results by means of a local center manifold calculation. Nevertheless, many questions have remained open, especially about the possibility of global bifurcations. Here we derive the system's stability diagram for the special case where the bimodal distribution consists of two equally weighted Lorentzians. Using an ansatz recently discovered by Ott and Antonsen, we show that in this case the infinite-dimensional problem reduces exactly to a flow in four dimensions. Depending on the parameters and initial conditions, the long-term dynamics evolves to one of three states: incoherence, where all the oscillators are desynchronized; partial synchrony, where a macroscopic group of phase-locked oscillators coexists with a sea of desynchronized ones; and a standing wave state, where two counter-rotating groups of phase-locked oscillators emerge. Analytical results are presented for the bifurcation boundaries between these states. Similar results are also obtained for the case in which the bimodal distribution is given by the sum of two Gaussians.

Voxel-wise comparisons of cellular microstructure and diffusion-MRI in mouse hippocampus using 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND).

A key challenge in medical imaging is determining a precise correspondence between image properties and tissue microstructure. This comparison is hindered by disparate scales and resolutions between medical imaging and histology. We present a new technique, 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND), for registering medical images with 3D histology to overcome these limitations. Ex vivo 120 × 120 × 200 µm resolution diffusion-MRI (dMRI) data was acquired at 7 T from adult C57Bl/6 mouse hippocampus. Tissue was then optically cleared using CLARITY and stained with cellular markers and confocal microscopy used to produce high-resolution images of the 3D-tissue microstructure. For each sample, a dense array of hippocampal landmarks was used to drive registration between upsampled dMRI data and the corresponding confocal images. The cell population in each MRI voxel was determined within hippocampal subregions and compared to MRI-derived metrics. 3D-BOND provided robust voxel-wise, cellular correlates of dMRI data. CA1 pyramidal and dentate gyrus granular layers had significantly different mean diffusivity (p > 0.001), which was related to microstructural features. Overall, mean and radial diffusivity correlated with cell and axon density and fractional anisotropy with astrocyte density, while apparent fibre density correlated negatively with axon density. Astrocytes, axons and blood vessels correlated to tensor orientation.

Prevention of early onset group B streptococcal disease by universal antenatal culture-based screening in all public hospitals in Hong Kong.

OBJECTIVES: To determine the prevalence of maternal colonization with group B streptococcus (GBS), and early onset GBS disease (EOGBSD) after implementation of universal screening. METHODS: This was a three-year retrospective cohort study on universal antenatal rectovaginal culture-based screening and intrapartum antimicrobial prophylaxis (IAP) to colonized women in the public sector in Hong Kong. Routinely collected data including maternal colonization and EOGBSD were retrieved. RESULTS: Of 113,989 GBS screening performed, 21.8% were positive. The colonization rate was higher in the public hospitals (higher risk) than in the Maternal and Child Health Centers (lower risk) (23.7% vs 18.1%, p < .001), while their false negative rates were not greater than expected. Majority of eligible women opted for screening, and colonized women received IAP. There were 29 cases of EOGBSD with clinical signs and a positive blood or cerebrospinal fluid culture. Compared to clinical risk-based screening, EOGBSD incidence decreased after universal screening (1 vs 0.24 per 1000 births, p < .001). Although EOGBSD occurred at a higher rate in preterm than term infants, 86.7% occurred in the latter, and were associated with a false negative screening result (41.3%), lack of screening (20.7%) or unavailability of a colonization result at labour (13.8%). CONCLUSIONS: Maternal GBS colonization rate was higher than previously reported, and varied with different risk populations. EOGBSD reduced after universal screening.

Non-invasive genetic imaging for molecular and cell therapies of cancer.

Gene therapy is a very attractive strategy in experimental cancer therapy. Ideally, the approach aims to deliver therapeutic genes selectively to cancer cells. However, progress in the improvement of gene therapy formulations has been hampered by difficulties in measuring transgene delivery and in quantifying transgene expression in vivo. In clinical trials, endpoints rely almost exclusively on the analysis of biopsies, which provide limited information. Non-invasive monitoring of gene delivery and expression is a very attractive approach as it can be repeated over time in the same patient to provide spatiotemporal information on gene expression on a whole body scale. Thus, imaging methods can uniquely provide researchers and clinicians the ability to directly and serially assess morphological, functional and metabolic changes consequent to molecular and cellular based therapies. This review highlights the various methods currently being developed in preclinical models.

Self-reported problem behavior in young children with and without a DSM-disorder in the general population.

BACKGROUND: Problem behavior of young children is generally not assessed with structured child interviews. This paper examined how information about problem behavior, obtained by structured interviews with six-year-old children, relates to DSM-disorders obtained from parents and to treatment referral. METHODS: In a population-based cohort, caregivers of 1084 young children (mean age 6.7 years) were interviewed with the DSM-based Diagnostic Interview Schedule-Young Child version (DISC-YC), and they scored the Child Behavior Checklist (CBCL). Children themselves were interviewed about problem behavior using the semi-structured Berkeley Puppet Interview (BPI). Information regarding treatment referral to mental health services was obtained by parent-reported questionnaire when children were on average eight years old. RESULTS: DSM-disorders and CBCL problems in the clinical range were cross-sectionally associated with higher levels of child self-reported problems. Associations were strongest in the externalizing domain (e.g. DISC-YC externalizing disorders with BPI externalizing scores: F(1, 416)=19.39, P<0.001; DISC-YC internalizing disorders with BPI internalizing scores: F(1, 312)=3.75, P=0.054). Moreover, higher BPI internalizing and externalizing problem scores predicted treatment referral two years later. CONCLUSIONS: We conclude that systematically interviewing preschool and young elementary school-aged children should be an integral part of child assessment. This approach may contribute to a better understanding of child development and may predict future problems.

9.4 T MR microscopy of the substantia nigra with pathological validation in controls and disease.

BACKGROUND: The anatomy of the substantia nigra on conventional MRI is controversial. Even using histological techniques it is difficult to delineate with certainty from surrounding structures. We sought to define the anatomy of the SN using high field spin-echo MRI of pathological material in which we could study the anatomy in detail to corroborate our MRI findings in controls and Parkinson's disease and progressive supranuclear palsy. METHODS: 23 brains were selected from the Queen Square Brain Bank (10 controls, 8 progressive supranuclear palsy, 5 Parkinson's disease) and imaged using high field 9.4 Tesla spin-echo MRI. Subsequently brains were cut and stained with Luxol fast blue, Perls stain, and immunohistochemistry for substance P and calbindin. Once the anatomy was defined on histology the dimensions and volume of the substantia nigra were determined on high field magnetic resonance images. RESULTS: The anterior border of the substantia nigra was defined by the crus cerebri. In the medial half it was less distinct due to the deposition of iron and the interdigitation of white matter and the substantia nigra. The posterior border was flanked by white matter bridging the red nucleus and substantia nigra and seen as hypointense on spin-echo magnetic resonance images. Within the substantia nigra high signal structures corresponded to confirmed nigrosomes. These were still evident in Parkinson's disease but not in progressive supranuclear palsy. The volume and dimensions of the substantia nigra were similar in Parkinson's disease and controls, but reduced in progressive supranuclear palsy. CONCLUSIONS: We present a histologically validated anatomical description of the substantia nigra on high field spin-echo high resolution magnetic resonance images and were able to delineate all five nigrosomes. In accordance with the pathological literature we did not observe changes in the nigrosome structure as manifest by volume or signal characteristics within the substantia nigra in Parkinson's disease whereas in progressive supranuclear palsy there was microarchitectural destruction.

Bending stiffness of a crystalline actin bundle.

The acrosomal process of the sperm of the horseshoe crab (Limulus polyphemus) is a unique crystalline actin bundle, consisting of multiple actin filaments cross-linked by the actin-bundling protein, scruin. For successful fertilization, the acrosomal bundle must penetrate through a 30 microm thick jelly coat surrounding the egg and thus it must be sufficiently stiff. Here, we present two measurements of the bending stiffness of a single crystalline bundle of actin. Results from these measurements indicate that the actin:scruin composite bundle has an average elastic modulus of 2 GPa, which is similar to that of a single actin filament, and a bending stiffness that is more than two orders of magnitude larger than that of a bundle of uncross-linked actin filaments due to stiffening by the scruin matrix.

Cloning and expression analysis of a mouse gene related to Drosophila odd-skipped.

The Drosophila pair-rule gene odd-skipped (odd) and two related genes, sister of odd (sob) and bowel (bowl), encode zinc finger containing proteins, two of which play important roles in embryonic development probably functioning as transcription factors. Here we report the cloning and expression analysis of a mouse gene related to odd, odd-skipped related 1 (Osr1). During early embryogenesis Osr1 is expressed in the intermediate mesoderm and in a dynamic pattern during limb and branchial arch development.

Veganism and its relationship with insulin resistance and intramyocellular lipid.

OBJECTIVE: To test the hypothesis that dietary factors in the vegan diet lead to improved insulin sensitivity and lower intramyocellular lipid (IMCL) storage. DESIGN: Case-control study. SETTING: Imperial College School of Medicine, Hammersmith Hospital Campus, London, UK. SUBJECTS: A total of 24 vegans and 25 omnivores participated in this study; three vegan subjects could not be matched therefore the matched results are shown for 21 vegans and 25 omnivores. The subjects were matched for gender, age and body mass index (BMI). INTERVENTIONS: Full anthropometry, 7-day dietary assessment and physical activity levels were obtained. Insulin sensitivity (%S) and beta-cell function (%B) were determined using the homeostatic model assessment (HOMA). IMCL levels were determined using in vivo proton magnetic resonance spectroscopy; total body fat content was assessed by bioelectrical impedance. RESULTS: There was no difference between the groups in sex, age, BMI, waist measurement, percentage body fat, activity levels and energy intake. Vegans had a significantly lower systolic blood pressure (-11.0 mmHg, CI -20.6 to -1.3, P=0.027) and higher dietary intake of carbohydrate (10.7%, CI 6.8-14.5, P<0.001), nonstarch polysaccharides (20.7 g, CI 15.8-25.6, P<0.001) and polyunsaturated fat (2.8%, CI 1.0-4.6, P=0.003), with a significantly lower glycaemic index (-3.7, CI -6.7 to -0.7, P=0.01). Also, vegans had lower fasting plasma triacylglycerol (-0.7 mmol/l, CI -0.9 to -0.4, P<0.001) and glucose (-0.4 mmol/l, CI -0.7 to -0.09, P=0.05) concentrations. There was no significant difference in HOMA %S but there was with HOMA %B (32.1%, CI 10.3-53.9, P=0.005), while IMCL levels were significantly lower in the soleus muscle (-9.7, CI -16.2 to -3.3, P=0.01). CONCLUSION: Vegans have a food intake and a biochemical profile that will be expected to be cardioprotective, with lower IMCL accumulation and beta-cell protective.

Surface biology of collagen scaffold explains blocking of wound contraction and regeneration of skin and peripheral nerves.

We review the details of preparation and of the recently elucidated mechanism of biological (regenerative) activity of a collagen scaffold (dermis regeneration template, DRT) that has induced regeneration of skin and peripheral nerves (PN) in a variety of animal models and in the clinic. DRT is a 3D protein network with optimized pore size in the range 20-125 µm, degradation half-life 14 ± 7 d and ligand densities that exceed 200 µM α1ß1 or α2ß1 ligands. The pore has been optimized to allow migration of contractile cells (myofibroblasts, MFB) into the scaffold and to provide sufficient specific surface for cell-scaffold interaction; the degradation half-life provides the required time window for satisfactory binding interaction of MFB with the scaffold surface; and the ligand density supplies the appropriate ligands for specific binding of MFB on the scaffold surface. A dramatic change in MFB phenotype takes place following MFB-scaffold binding which has been shown to result in blocking of wound contraction. In both skin wounds and PN wounds the evidence has shown clearly that contraction blocking by DRT is followed by induction of regeneration of nearly perfect organs. The biologically active structure of DRT is required for contraction blocking; well-matched collagen scaffold controls of DRT, with structures that varied from that of DRT, have failed to induce regeneration. Careful processing of collagen scaffolds is required for adequate biological activity of the scaffold surface. The newly understood mechanism provides a relatively complete paradigm of regenerative medicine that can be used to prepare scaffolds that may induce regeneration of other organs in future studies.