Bronchogenic Cyst in Infants-Clinical and Histopathological Features.

A male infant, one month old, weight 4000 g, breastfed only, no pathological history, was admitted to the 2nd Pediatric Clinic, Clinical Emergency County Hospital in Craiova with fever and cough. Clinical findings when he was admitted: fever 38.7°C, perioral cyanosis, spastic cough, expiratory dyspnea, intercostal retraction, polypnea, subcrepitant rales in the right lung area. The chest x-ray revealed pneumonia aspect in the right middle perihilar region. He was administered antibiotic treatment, HHC, antithermics, with a favorable evolution. The control x-ray, when the infant was in a fair general state, with no disease symptomatology, pointed out a cystic formation at the level of the right middle lobe. The pulmonary CT revealed cavitary lesion, with a diameter of about 40mm in the right lung, and with the presence of septa to the interior and air content. The infant was urgently transferred to Marie Curie Hospital in Bucharest, where the cyst formation was removed through a surgical procedure. The anatomo-pathological examination revealed a bronchogenic cyst. The evolution was favorable after the surgical procedure.

An analytical model to design circumferential clasps for laser-sintered removable partial dentures.

OBJECTIVE: Clasps of removable partial dentures (RPDs) often suffer from plastic deformation and failure by fatigue; a common complication of RPDs. A new technology for processing metal frameworks for dental prostheses based on laser-sintering, which allows for precise fabrication of clasp geometry, has been recently developed. This study sought to propose a novel method for designing circumferential clasps for laser-sintered RPDs to avoid plastic deformation or fatigue failure. METHODS: An analytical model for designing clasps with semicircular cross-sections was derived based on mechanics. The Euler-Bernoulli elastic curved beam theory and Castigliano's energy method were used to relate the stress and undercut with the clasp length, cross-sectional radius, alloy properties, tooth type, and retention force. Finite element analysis (FEA) was conducted on a case study and the resultant tensile stress and undercut were compared with the analytical model predictions. Pull-out experiments were conducted on laser-sintered cobalt-chromium (Co-Cr) dental prostheses to validate the analytical model results. RESULTS: The proposed circumferential clasp design model yields results in good agreement with FEA and experiments. The results indicate that Co-Cr circumferential clasps in molars that are 13mm long engaging undercuts of 0.25mm should have a cross-section radius of 1.2mm to provide a retention of 10N and to avoid plastic deformation or fatigue failure. However, shorter circumferential clasps such as those in premolars present high stresses and cannot avoid plastic deformation or fatigue failure. SIGNIFICANCE: Laser-sintered Co-Cr circumferential clasps in molars are safe, whereas they are susceptible to failure in premolars.

Strategies for Optimizing the Soft Tissue Seal around Osseointegrated Implants.

Percutaneous and permucosal devices such as catheters, infusion pumps, orthopedic, and dental implants are commonly used in medical treatments. However, these useful devices breach the soft tissue barrier that protects the body from the outer environment, and thus increase bacterial infections resulting in morbidity and mortality. Such associated infections can be prevented if these devices are effectively integrated with the surrounding soft tissue, and thus creating a strong seal from the surrounding environment. However, so far, there are no percutaneous/permucosal medical devices able to prevent infection by achieving strong integration at the soft tissue-device interface. This review gives an insight into the current status of research into soft tissue-implant interface and the challenges associated with these interfaces. Biological soft/hard tissue interfaces may provide insights toward engineering better soft tissue interfaces around percutaneous devices. In this review, focus is put on the history and current findings as well as recent progress of the strategies aiming to develop a strong soft tissue seal around osseointegrated implants, such as orthopedic and dental implants.

Caloric restriction stabilizes body weight and accelerates behavioral recovery in aged rats after focal ischemia.

Obesity and hyperinsulinemia are risk factors for stroke. We tested the hypothesis that caloric restriction, which reduces the incidence of age-related obesity and metabolic syndrome, may represent an efficient and cost-effective strategy for preventing stroke and its devastating consequences. To this end, we placed aged, obese Sprague-Dawley aged rats on a calorie-restricted diet for 8 weeks prior to the experimental infarction. Stroke in this animal model caused a progressive decrease in weight that reached a minimum at day 6 for the young rats, and at day 10 for the aged, ad libitum-fed rats. However, in aged animals that were calorie-restricted prior to stroke, body weight did not decrease after stroke, but we noted accelerated body weight gain shortly thereafter starting at day 5 poststroke. Moreover, calorie-restricted aged animals showed improved behavioral recovery in tasks requiring complex sensorimotor skills, or in tasks requiring cutaneous sensitivity and sensorimotor integration or spatial memory. Likewise, calorie-restricted aged rats showed significant poststroke increases in serum glucose, insulin, and IGF1 levels, as well as CR-specific changes in the expression of gene transcripts involved in glycogen metabolism, IGF signaling, apoptosis, arteriogenesis, and hypoxia. In conclusion, our study shows that recovery from stroke is enhanced in aged rats by a dietary regimen that reduces body weight prior to infarct.

Molecular mechanisms underlying neurodevelopmental disorders, ADHD and autism.

Neurodevelopmental disorders such as attention deficit hyperactivity disorder and autism represent a significant economic burden, which justify vigorous research to uncover its genetics and developmental clinics for a diagnostic workup. The urgency of addressing attention deficit hyperactivity disorder comorbidities is seen in the chilling fact that attention deficit hyperactivity disorder (ADHD), mood disorders, substance use disorders and obesity each increase the risk for mortality. However, data about comorbidity is mainly descriptive, with mechanistic studies limited to genetic epidemiological studies that document shared genetic risk factors among these conditions. Autism and intellectual disability affects 1.5 to 2% of the population in Western countries with many individuals displaying social-emotional agnosia and having difficulty in forming attachments and relationships. Underlying mechanisms include: (i) dysfunctions of neuronal miRNAs; (ii) deletions in the chromosome 21, subtelomeric deletions, duplications and a maternally inherited duplication of the chromosomal region 15q11-q13; (iii) microdeletions in on the long (q) arm of the chromosome in a region designated q21.1 increases the risk of delayed development, intellectual disability, physical abnormalities, and neurological and psychiatric problems associated with autism, schizophrenia, and epilepsy and weak muscle tone (hypotonia); (iv) interstitial duplications encompassing 16p13.11.

Development of a Large Animal Long-Term Intervertebral Disc Organ Culture Model That Includes the Bony Vertebrae for Ex Vivo Studies.

Intervertebral disc (IVD) degeneration is a common cause of low back pain. Testing potential therapeutics in the regeneration of the disc requires the use of model systems. Although several animal models have been developed to investigate IVD degeneration, they are technically challenging to prepare, expensive, present with limitations when performing biomechanical studies on the disc, and are impractical in large-scale screening of novel anabolic and scaffolding agents. An IVD organ culture system offers an inexpensive alternative. In the current paradigm, the bony endplates are removed to allow for nutrient diffusion and maintenance of disc cell viability. Although this is an excellent system for testing biologics, it results in concave cartilage endplates and, as such, requires special platens for loading purposes in a bioreactor as flat ones can overload the annular disc region leading to improper loading. Furthermore, the absence of bone makes it unsuitable for applying complex cyclic loading, a topic of interest in the study of chronic progressive degeneration, as multiaxial loading is more representative of daily forces encountered by the IVD. We have developed and validated a novel long-term IVD organ culture model that retains vertebral bone and is easy to prepare. Our model is ideal for testing potential drugs and alternate-based therapies, in addition to investigating the long-term effects of loading paradigms on disc degeneration and repair.

Age-related hypoxia in CNS pathology.

Although neuropathological conditions differ in the etiology of the inflammatory response, cellular and molecular mechanisms of neuroinflammation are probably similar in aging, hypertension, depression and cognitive impairment. Moreover, a number of common risk factors such as obesity, hypertension, diabetes and atherosclerosis are increasingly understood to act as "silent contributors" to neuroinflammation and can underlie the development of disorders such as cerebral small vessel disease (cSVD) and subsequent dementia. On the other hand, acute neuroinflammation, such as in response to traumatic or cerebral ischemia, aggravates the acute damage and can lead to a number of pathological such as depression, post-stroke dementia and potentially neurodegeneration. All of those sequelae impair recovery and most of them provide the ground for further cerebrovascular events and a vicious cycle develops. Therefore, understanding the mechanisms associated with vascular dementia, stroke and related complications is of paramount importance in improving current preventive and therapeutic interventions. Likewise, understanding of molecular factors and pathways associated with neuroinflammation will eventually enable the discovery and implementation of new diagnostic and therapeutic strategies indicated in a wide range of neurological conditions.

Diagenesis-inspired reaction of magnesium ions with surface enamel mineral modifies properties of human teeth.

UNLABELLED: Mineralized tissues such as teeth and bones consist primarily of highly organized apatitic calcium-phosphate crystallites within a complex organic matrix. The dimensions and organization of these apatite crystallites at the nanoscale level determine in part the physical properties of mineralized tissues. After death, geological processes such as diagenesis and dolomitization can alter the crystallographic properties of mineralized tissues through cycles of dissolution and re-precipitation occurring in highly saline environments. Inspired by these natural exchange phenomena, we investigated the effect of hypersalinity on tooth enamel. We discovered that magnesium ions reacted with human tooth enamel through a process of dissolution and re-precipitation, reducing enamel crystal size at the surface of the tooth. This change in crystallographic structure made the teeth harder and whiter. Salt-water rinses have been used for centuries to ameliorate oral infections; however, our discovery suggests that this ancient practice could have additional unexpected benefits. STATEMENT OF SIGNIFICANCE: Here we describe an approach inspired by natural geological processes to modify the properties of a biomineral - human tooth enamel. In this study we showed that treatment of human tooth enamel with solutions saturated with magnesium induced changes in the nanocrystals at the outer surface of the protective enamel layer. As a consequence, the physical properties of the tooth were modified; tooth microhardness increased and the color shade became whiter, thus suggesting that this method could be used as a clinical treatment to improve dental mechanical properties and esthetics. Such an approach is simple and straightforward, and could also be used to develop new strategies to synthesize and modify biominerals for biomedical and industrial applications.

Up-regulation of serotonin receptor 2B mRNA and protein in the peri-infarcted area of aged rats and stroke patients.

Despite the fact that a high proportion of elderly stroke patients develop mood disorders, the mechanisms underlying late-onset neuropsychiatric and neurocognitive symptoms have so far received little attention in the field of neurobiology. In rodents, aged animals display depressive symptoms following stroke, whereas young animals recover fairly well. This finding has prompted us to investigate the expression of serotonin receptors 2A and 2B, which are directly linked to depression, in the brains of aged and young rats following stroke. Although the development of the infarct was more rapid in aged rats in the first 3 days after stroke, by day 14 the cortical infarcts were similar in size in both age groups i.e. 45% of total cortical volume in young rats and 55.7% in aged rats. We also found that the expression of serotonin receptor type B mRNA was markedly increased in the perilesional area of aged rats as compared to the younger counterparts. Furthermore, histologically, HTR2B protein expression in degenerating neurons was closely associated with activated microglia both in aged rats and human subjects. Treatment with fluoxetine attenuated the expression of Htr2B mRNA, stimulated post-stroke neurogenesis in the subventricular zone and was associated with an improved anhedonic behavior and an increased activity in the forced swim test in aged animals. We hypothesize that HTR2B expression in the infarcted territory may render degenerating neurons susceptible to attack by activated microglia and thus aggravate the consequences of stroke.

Post-stroke gaseous hypothermia increases vascular density but not neurogenesis in the ischemic penumbra of aged rats.

PURPOSE: In aged humans, stroke is a major cause of disability for which no neuroprotective measures are available. In animal studies of focal ischemia, short-term hypothermia often reduces infarct size. Nevertheless, efficient neuroprotection requires long-term, regulated lowering of whole body temperature. Previously, we reported that post-stroke exposure to hydrogen sulfide (H2S) effectively lowers whole body temperature and confers neuroprotection in aged animals. METHODS: In the present study using behavioral tests, MRI, telemetrical EEG, BP and temperature recordings, RT-PCR and immunofluorescence, we assessed infarct size, vascular density, neurogenesis and as well as the expression of genes coding for proteasomal proteins as well as in post-stroke aged Sprague-Dawley rats exposed to H2S- induced hypothermia. RESULTS: Two days exposure to mild hypothermia diminishes the expression of several genes involved in protein degradation, thereby leading to better preservation of infarcted tissue. Further, hypothermia increased the density of newly formed blood vessels in the peri-lesional cortex did not enhance neurogenesis in the infarcted area of aged rats. Likewise, there was improved recovery of fine vestibulomotor function and asymmetric sensorimotor deficit. CONCLUSION: Long-term hypothermia may be a viable clinical approach by simultaneously targeting multiple processes including better tissue preservation, enhanced vascular density and improved behavioral performance.

Granulocyte colony-stimulating factor and bone marrow mononuclear cells for stroke treatment in the aged brain.

Ischemic stroke swiftly induces a wide spectrum of pathophysiological sequelae, particularly in the aged brain. The translational failure of experimental therapies, might partially be related to monotherapeutic approaches, not address potential counter-mechanisms sufficiently or within the best time window. For example, therapeutic effects relying on stem/progenitor cell mobilization by granulocyte-colony stimulating factor (G-CSF), require approximately a week to become manifest, which is potentially beyond the optimal timing. Here, We tested the hypothesis that treating post-stroke aged rats with the combination of bone marrow-derived mononuclear cells (BM MNC) and G-CSF improves the long term (56 days) functional outcome by compensating the delay before G-CSF effects come to full effect. 1x10(6) syngeneic BM MNC per kg bodyweight (BW) with G-CSF (50 µg/kg, given intraperitoneal by via the jugular vein to aged Sprague- Dawley rats, six hours post-stroke. This process was repeated daily, for a 28 day period. Infarct volume was measured by magnetic resonance imaging at 3 and 48 days post-stroke and additionally by immunohistochemistry at day 56. Functional recovery was tested during the entire post-stroke survival period. Daily G-CSF treatment led to a robust and consistent improvement of neurological function, but did not alter final infarct volumes. The combination of G-CSF and BM MNC, did not further improve post-stroke recovery. The lack of an additional benefit may be due to interaction between both approaches, and to a lesser extent, in the insensitivity of the aged brains' regenerative mechanisms. Also considering recent findings on other tandem approaches involving G-CSF in animal models featuring relevant co-morbidities, we conclude that such combination therapies are not the optimal approach to treat the acutely injured aged brain.

Life style, Perfusion deficits and Co-morbidities Precipitate Inflammation and Cerebrovascular Disorders in Aged Subjects.

Cerebrovascular diseases represent 2nd leading cause of death worldwide. Understanding how genetic predispositions and their interaction with environmental factors affect cerebrovascular diseases is fundamental for prevention, diagnosis and for the development of safe and efficient therapies. Cerebrovascular diseases have not only a very high mortality rate, but also results in debilitating neurological impairments or permanent disability in survivors associated with huge economic losses. Among the women and men individuals with a low-risk lifestyle (smoking, exercising daily, consuming a prudent diet including moderate alcohol and having a healthy weight during mid-life) had a significantly lower risk of stroke than individuals without a low-risk lifestyle. Current review focuses on determining the relationship between diet, as an important component of 'life style', aging and cerebrovascular diseases.This review may help to unravel biological mechanisms linking lifestyle, diet-induced, metabolic inflammation, aging and cerebral hypoperfusion to development of cerebrovascular diseases, a prerequisite for development of science-based preventive strategies needed to combat the major public health challenges like obesity and stroke.

Naproxen affects osteogenesis of human mesenchymal stem cells via regulation of Indian hedgehog signaling molecules.

INTRODUCTION: We previously showed that type X collagen, a marker of late stage chondrocyte hypertrophy (associated with endochondral ossification), is constitutively expressed by mesenchymal stem cells (MSCs) from osteoarthritis patients and this may be related to Naproxen (Npx), a nonsteroidal anti-inflammatory drug used for therapy. Hedgehog (HH) signaling plays an important role during the development of bone. We tested the hypothesis that Npx affected osteogenic differentiation of human MSCs through the expression of Indian hedgehog (IHH), Patched-1 (PTC1) and GLI family members GLI1, GLI2, GLI3 in vitro. METHODS: MSCs were cultured in osteogenic differentiation medium without (control) or with 0.5 µM Npx. The expression of collagen type X, alpha 1 (COL10A1), alkaline phosphatase (ALP), osteopontin (OPN), osteocalcin (OC), collagen type I, alpha 1 (COL1A1) was analyzed with real-time reverse transcription (RT) PCR, and the ALP activity was measured. The osteogenesis of MSCs was monitored by mineral staining and quantification with alizarin red S. To examine whether Npx affects osteogenic differentiation through HH signaling, the effect of Npx on the expression of IHH, GLI1, GLI2, GLI3 and PTC1 was analyzed with real-time RT PCR. The effect of cyclopamine (Cpn), a HH signaling inhibitor, on the expression of COL10A1, ALP, OC and COL1A1 was also determined. RESULTS: When MSCs were cultured in osteogenic differentiation medium, Npx supplementation led to a significant decrease in ALP gene expression as well as its activity, and had a tendency to decrease mineral deposition. It also decreased the expression of COL1A1 significantly. In contrast, the gene expression of COL10A1 and OPN were upregulated significantly by Npx. No significant effect was found on OC expression. The expression of IHH, PTC1, GLI1, and GLI2 was increased by Npx, while no significant difference was observed on GLI3 expression. Cpn reversed the effect of Npx on the expression of COL10A1, ALP, OPN and COL1A1. CONCLUSIONS: These results indicate that Npx can affect gene expression during osteogenic differentiation of MSCs, and downregulate mineral deposition in the extracellular matrix through IHH signaling. Therefore, Npx could affect MSC-mediated repair of subchondral bone in OA patients.

Regulated fracture in tooth enamel: a nanotechnological strategy from nature.

Tooth enamel is a very brittle material; however it has the ability to sustain cracks without suffering catastrophic failure throughout the lifetime of mechanical function. We propose that the nanostructure of enamel can play a significant role in defining its unique mechanical properties. Accordingly we analyzed the nanostructure and chemical composition of a group of teeth, and correlated it with the crack resistance of the same teeth. Here we show how the dimensions of apatite nanocrystals in enamel can affect its resistance to crack propagation. We conclude that the aspect ratio of apatite nanocrystals in enamel determines its resistance to crack propagation. According to this finding, we proposed a new model based on the Hall-Petch theory that accurately predicts crack propagation in enamel. Our new biomechanical model of enamel is the first model that can successfully explain the observed variations in the behavior of crack propagation of tooth enamel among different humans.

Effect of acetaminophen and nonsteroidal anti-inflammatory drugs on gene expression of mesenchymal stem cells.

We have previously shown that mesenchymal stem cells (MSCs) from patients with osteoarthritis (OA) constitutively express type X collagen, a marker of late-stage chondrocyte hypertrophy, osteogenic marker genes, including alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OC), and chondrogenesis marker gene aggrecan (ACAN). As patients with arthritis often take nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (Acet), the purpose of the study was to assess whether these drugs can affect the gene expression of human MSCs. MSCs isolated from the bone marrow of patients with OA or normal donors were cultured without (control) or with Acet or NSAIDs, which include ibuprofen, diclofenac (Dic), naproxen, and celebrex. After 3 days of culture, the expression of type X collagen alpha 1 (COL10A1), ACAN, COL1A1, as well as ALP, BSP, OC, and Runt-related transcription factor 2 was analyzed by real-time reverse transcription (RT)-polymerase chain reaction. The results showed that COL10A1 and the osteogenic and chondrogenic marker genes can be regulated by NSAIDs and Acet in normal MSCs. In contrast, Acet did not significantly affect COL10A1 expression in OA MSCs, while Dic is the only drug that had no significant effect on all markers in normal MSCs. The upregulation of COL10A1 in normal MCSs by Acet and Npx may explain why stem cells from patients with OA express COL10A1 constitutively. This knowledge may help in designing better strategies for stem cell differentiation into chondrocyte-like cells, from this source, with Dic being a viable option for treating OA pain, with an eye toward preventing the potential to enhance calcification in the repair of cartilage and degenerated intervertebral discs.

Regulation of enamel hardness by its crystallographic dimensions.

Enamel is a composite biomaterial comprising a minor organic matrix (~2%) and a hierarchically organized inorganic ultrastructure (~96-98%). Surprisingly, to date there is no available information in the literature regarding the possible role of the enamel ultrastructure on the nanoscale level in tooth macroscopic properties. Understanding this relationship is of special interest for restorative purposes in dentistry. Accordingly, this study was designed to investigate how enamel nanocrystals regulate its hardness. We performed microindentation analysis on 100 extracted human teeth. The tooth enamel hardness was quantified and correlated with changes in enamel chemical composition and crystallographic dimensions obtained from Fourier transform infrared spectroscopy and X-ray diffraction, respectively. Enamel hardness was not related to the variability in organic content, but was associated with the size of apatite crystals along the c-axis. This association followed the Hall-Petch model for polycrystalline materials, indicating that the optimal size of apatite nanocrystals (larger than the critical size) provides enamel with the greatest hardness, which enables teeth to survive the heavy wear over a human lifetime.