Bone tissue engineering in osteoporosis

Osteoporosis is a polygenetic, environmentally modifiable disease, which precipitates into fragility fractures of vertebrae, hip and radius and also confers a high risk of fractures in accidents and trauma. Aging and the genetic molecular background of osteoporosis cause delayed healing and impair regeneration. The worldwide burden of disease is huge and steadily increasing while the average life expectancy is also on the rise. The clinical need for bone regeneration applications, systemic or in situ guided bone regeneration and bone tissue engineering, will increase and become a challenge for health care systems. Apart from in situ guided tissue regeneration classical ex vivo tissue engineering of bone has not yet reached the level of routine clinical application although a wealth of scaffolds and growth factors has been developed. Engineering of complex bone constructs in vitro requires scaffolds, growth and differentiation factors, precursor cells for angiogenesis and osteogenesis and suitable bioreactors in various combinations. The development of applications for ex vivo tissue engineering of bone faces technical challenges concerning rapid vascularization for the survival of constructs in vivo. Recent new ideas and developments in the fields of bone biology, materials science and bioreactor technology will enable us to develop standard operating procedures for ex vivo tissue engineering of bone in the near future. Once prototyped such applications will rapidly be tailored for compromised conditions like vitamin D and sex hormone deficiencies, cellular deficits and high production of regeneration inhibitors, as they are prevalent in osteoporosis and in higher age.     

Do low birth weight infants not see eyes? Face recognition in infancy

BackgroundProgress in neonatal medicine has dramatically improved the survival rate of preterm births, but the evidence suggests that these low-birth weight infants (LBWIs) go on to develop pervasive development disorders and attention deficit hyperactivity disorder (ADHD) at greater rates than the general population. Children with neurodevelopmental disorders are known to suffer from deficits in visual cognition, such as in face perception and attentional functions, the characteristics of which already manifest in early infancy.PurposeThis study aimed to investigate visual cognition in LBWIs during infancy.Subjects20 LBWIs and 20 normal-birth-weight infants (NBWIs: control) of age 9–10 months (corrected age was used for LBWIs).MethodChildren were held seated in front of an eye tracking system by a parent, and presented with facial photos as visual stimuli. During the familiarization phase, the child was presented with two images of the same human face (familiarization stimulus) on the left and right side of a display screen (5 × 10 s trials). Next, during the test phase, the child was presented with the same image on one side of the screen, and a photo of a different person’s face (novel stimulus) on the other (2 × 5 s trials). Gaze behavior was assessed in terms of the total time spent looking at either facial stimulus, and specifically at the eyes of the stimuli, as well as the number of attentional shifts between stimuli, and novelty preference.Results/DiscussionLBWIs spent significant less time looking at facial stimuli overall, and less time at the eye region, than NBWIs. These findings seem to evidence developmental differences in functions related to visual cognition.     

Novel ACOX1 mutations in two siblings with peroxisomal acyl-CoA oxidase deficiency

Peroxisomal acyl-CoA oxidase (ACOX1) deficiency is a rare autosomal recessive single enzyme deficiency characterized by hypotonia, seizures, failure to thrive, developmental delay, and neurological regression starting from approximately 3 years of age.Here, we report two siblings with ACOX1 deficiency born to non-consanguineous Japanese parents. They showed mild global developmental delay from infancy and began to regress at 5 years 10 months and 5 years 6 months of age respectively. They gradually manifested with cerebellar ataxia, dysarthria, pyramidal signs, and dysphasia. Brain MRI revealed T2 high-intensity areas in the cerebellar white matter, bilateral middle cerebellar peduncle, and transverse tracts of the pons, followed by progressive atrophy of these areas.Intriguingly, the ratios of C24:0, C25:0, and C26:0 to C22:0 in plasma, which usually increase in ACOX1 deficiency were within normal ranges in both patients. On the other hand, whole exome sequencing revealed novel compound heterozygous variants in ACOX1: a frameshift variant (c.160delC:p.Leu54Serfs*18) and a missense variant (c.1259 T > C:p.Phe420Ser). The plasma concentration of individual very long chain fatty acids (C24:0, C25:0, and C26:0) was elevated, and we found that peroxisomes in fibroblasts of the patients were larger in size and fewer in number as previously reported in patients with ACOX1 deficiency. Furthermore, the C24:0 β-oxidation activity was dramatically reduced.Our findings suggest that the elevation of individual plasma very long chain fatty acids concentration, genetic analysis including whole exome analysis, and biochemical studies on the patient’s fibroblasts should be considered for the correct diagnosis of ACOX1 deficiency.     

Postoperative improvement of executive function and adaptive behavior in children with intractable epilepsy

IntroductionAn alteration in postoperative cognitive function varies according to the patients’ background characteristics, such as etiology, focus, and seizure duration. Accurate prediction and assessment of postoperative cognitive function is difficult in each patient. Adaptive behavior could describe the typical performance of daily activities and represents the ability to translate cognitive potential into real-world skills. We examined the relationship between alterations of executive function (EF) and adaptive behavior in school children undergoing surgery for intractable epilepsy.MethodologyWe enrolled 31 children with focal resection or corpus callosotomy for intractable epilepsy [mean age at surgery, 12.5 years; 16 boys; mean intellectual quotient, 73.3]. We surveyed answered questionnaires on attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and adaptive behavior using the Vineland Adaptive Behavior Scale, 2nd edition (VABS-II), and performed continuous performance tests (CPTs) on children pre- and postoperatively.ResultADHD and ASD symptoms improved after epilepsy surgery. The omission error (OE) in the CPT variable improved after epilepsy surgery, especially in children with a shorter preoperative period. Improved ASD symptoms led to an increased score of the coping skills subdomain. The reduced OE observed after surgery also increased the score of the community skills subdomain.ConclusionImprovement in EF and ASD symptoms resulted in better adaptive behavior postoperatively. These results were important for the pre- and postoperative evaluation and re-evaluation of children with epilepsy requiring special education and related services.     

An anatomic study of the inferior oblique nerve with high-resolution magnetic resonance imaging

Objective

To investigate anatomic features of the inferior oblique nerve (IObN) by high-resolution magnetic resonance (MR) imaging and cadaveric dissection.

Methods

This study enrolled 100 consecutive outpatients, who underwent 3.0 T MR imaging equipped by the 32-channel head coil. The T2-weighted imaging data of IObN were extracted for analysis and compared with the findings of microsurgical dissection in 14 orbits.

Results

50 male and 50 female subjects allotted to the imaging study were aged from 11 to 78 years. In 94 % sides, the IObN was found to separate from the inferior rectus muscle (IRM) at the level just behind to the posterior pole of the bulb. At the midpoint of the IObN part coursing along the orbital floor and above or adjacent to the infraorbital nerve and artery complex, the mean distance from the lateral margin of the IRM was 1.0 mm on the right and 0.9 mm on the left. The IObN showed upward direction change just below the belly of the inferior oblique muscle and innervated to it at the equator level in 78 sides on the right and 89 on the left. Dissected specimens revealed the consistent morphological findings of the IObN.

Conclusions

The IObN seems to be a relatively consistent structure. Anatomic information on the IObN and surrounding structures that are provided by high-resolution MR imaging can be a help for safe surgery.     

Characteristics of gram-negative bacteremia during febrile neutropenia among allogeneic hematopoietic stem cell transplant recipients on levofloxacin prophylaxis

European Journal of Clinical Microbiology & Infectious Diseases - The aim of this study is to clarify the characteristics of gram-negative bacteremia (GNB), including extended-spectrum...     

Imaging of muscle activity-induced morphometric changes in fibril network of myofascia by two-photon microscopy

Myofascia, deep fascia enveloping skeletal muscles, consists of abundant collagen and elastin fibres that play a key role in the transmission of muscular forces. However, understanding of biomechanical dynamics in myofascia remains very limited due to less quantitative and relevant approaches for in vivo examination. The purpose of this study was to evaluate the myofascial fibril structure by means of a quantitative approach using two-photon microscopy (TPM) imaging in combination with intravital staining of Evans blue dye (EBD), a far-red fluorescence dye, which potentially labels elastin. With focus on myofascia of the tibial anterior (TA) muscle, the fibril structure intravitally stained with EBD was observed at the depth level of collagen fibrous membrane above the muscle belly. The EBD-labelled fibril structure and orientation in myofascia indicated biomechanical responses to muscle activity and ageing. The orientation histograms of EBD-labelled fibrils were significantly modified depending upon the intensity of muscle activity and ageing. Moreover, the density of EBD-labelled fibrils in myofascia decreased with habitual exercise but increased with muscle immobilization or ageing. In particular, the diameter of EBD-labelled fibrils in aged mice was significantly higher. The orientation histograms of EBD-labelled fibrils after habitual exercise, muscle immobilization and ageing showed significant differences compared to control. Indeed, the histograms in bilateral TA myofascia of exercise mice made simple waveforms without multiple sharp peaks, whilst muscular immobilization or ageing significantly shifted a histogram with sustaining multiple sharp peaks. Therefore, the dynamics of fibre network with EBD fluorescence in response to the biomechanical environment possibly indicate functional tissue adaptation in myofascia. Furthermore, on the basis of the knowledge that neutrophil recruitment occurs locally in working muscles, we suggested the unique reconstruction mechanism involving neutrophilic elastase in the myofascial fibril structure. In addition to the elastolytic susceptibility of EBD-labelled fibrils, distinct immunoreactivities and activities of neutrophil elastase in the myofascia were observed after electric pulse stimulation-induced muscle contraction for 15 min. Our findings of EBD-labelled fibril dynamics in myofascia through quantitative approach using TPM imaging and intravital fluorescence labelling potentially brings new insights to examine muscle physiology and pathology.     

Topographical relationship between the accessory hepatic duct and the hepatic artery system

Anatomical Science International - Hepatic biliary injury is one of the most common complications in cholecystectomy and is frequently accompanied by arterial injuries. Because there are several...