Αρχειοθήκη ιστολογίου

Δευτέρα 28 Δεκεμβρίου 2015

Spatial variation in osteon population density at the human femoral midshaft: histomorphometric adaptations to habitual load environment

Abstract

Intracortical remodeling, and the osteons it produces, is one aspect of the bone microstructure that is influenced by and, in turn, can influence its mechanical properties. Previous research examining the spatial distribution of intracortical remodeling density across the femoral midshaft has been limited to either considering only small regions of the cortex or, when looking at the entirety of the cortex, considering only a single individual. This study examined the spatial distribution of all remodeling events (intact osteons, fragmentary osteons, and resorptive bays) across the entirety of the femoral midshaft in a sample of 30 modern cadaveric donors. The sample consisted of 15 males and 15 females, aged 21–97 years at time of death. Using geographic information systems software, the femoral cortex was subdivided radially into thirds and circumferentially into octants, and the spatial location of all remodeling events was marked. Density maps and calculation of osteon population density in cortical regions of interest revealed that remodeling density is typically highest in the periosteal third of the bone, particularly in the lateral and anterolateral regions of the cortex. Due to modeling drift, this area of the midshaft femur has some of the youngest primary tissue, which consequently reveals that the lateral and anterolateral regions of the femoral midshaft have higher remodeling rates than elsewhere in the cortex. This is likely the result of tension/shear forces and/or greater strain magnitudes acting upon the anterolateral femur, which results in a greater amount of microdamage in need of repair than is seen in the medial and posterior regions of the femoral midshaft, which are more subject to compressive forces and/or lesser strain magnitudes.



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Clinical significance of accounting for tissue heterogeneity in permanent breast seeds implant brachytherapy planning

Publication date: Available online 23 December 2015
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Shahram Mashouf, Emmanuelle Fleury, Priscilla Lai, Tomas Merino, Eli Lechtman, Alex Kiss, Claire McCann, Jean-Philippe Pignol
PurposeThe Inhomogeneity Correction Factor (ICF) method provides heterogeneity correction for the fast calculation TG43 formalism in seeds brachytherapy. This study compared ICF corrected plans to their standard TG43 counterparts looking at their capacity to assess inadequate coverage and/or risk of any skin toxicities for patients who received Permanent Breast Seed Implant (PBSI).Methods and MaterialsThe 2 month post implant CT-scans and plans of 140 PBSI patients were used to calculate dose distributions using the TG-43U1 formalism and the ICF method. Multiple dose-volume histogram (DVH) parameters of clinical target volume (CTV) and skin were extracted and compared for both ICF and TG43 dose distributions. Short term (desquamation and erythema) and long term (telangiectasia) skin toxicity data were available on 125 and 110 of the patients, respectively, at the time of study. The predictive value of each DVH parameter of skin was evaluated using the area under the receiver operating characteristic (ROC) curve for each toxicity endpoint.ResultsThe DVH parameters of CTV calculated using the ICF method showed an overall decrease compared to TG43 while those of skin showed an increase confirming previously reported findings on the impact of heterogeneity with low energy sources. The ICF methodology enabled us to distinguish patients for whom the CTV V100 and V90 are up to 19% lower compared to TG43, which could present a risk of recurrence not detected when heterogeneity are not accounted for. The ICF method also led to an increase in the prediction of desquamation, erythema, and telangiectasia91% of skin DVH parameters studied.ConclusionsThe ICF methodology has the advantage to distinguish any inadequate dose coverage of CTV due to breast heterogeneity, which can be missed by TG43. The use of the ICF correction also led to an increase in prediction accuracy of skin toxicities in majority of cases.

Teaser

In this study we compared a tissue heterogeneity correction algorithm (ICF method) to the standard AAPM-TG43 protocol for a cohort of patients treated with permanent breast seed implants (PBSI). Using heterogeneity correction enabled distinguishing patients who received lower dose to the clinical target volume (CTV), who would otherwise go undetected using TG43. The use of the ICF correction also led to an increase in prediction accuracy of skin toxicities in the majority of the cases.


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The Best Medical Technologies of 2015

As we look back on the medtech developments of 2015 there's definitely a sense that we're living through revolutionary times. Nearly every day exciting and fascinating technologies are being unveiled by small and large companies, universities, and even tiny independent groups. Empowered by high-powered computers, 3D printers, and other technologies, researchers, scientists, and engineers are coming up with novel solutions to age-old medical problems. Everything from treating gunshot wounds to how fetuses inside the womb are monitored is going through change thanks to technologies developed by thousands of independent minds around the world.

And so we'd like to take you on a quick tour of amazing, inspiring, and long hoped for medical capabilities that have graced these pages over the last year.

Eyes-On Wearable Ultrasound and Infrared Glasses

Evena-wearable-ultrasound

Who would have thought we'd have hands-free and at-a-distance ultrasound technology in a pair of glasses? Evena Medical released their Eyes-On device that projects both ultrasound waves and infrared light to visualize both the peripheral and deeper vasculature for venipuncture procedures. The glasses feature Epson's Moverio technology that displays an image laid over the wearer's field of view. The computer that powers the glasses does image processing on the imaging data, detecting the vasculature and displaying it over the patient's skin within the glasses.

Here's what you would see wearing the glasses when imaging the peripheral vasculature using infrared:

 

Nanoparticles and Vascular Stents for Busting Brain Clots

clot-busting-nano-drugsThe field of nanomedicine has seen considerable progress this year in attacking its main target, cancer, but also in addressing other difficult conditions. Researchers at Harvard's Wyss Institute and University of Massachusetts' New England Center for Stroke Research combined a narrow stent with pressure activated nanoparticles to break up vessel occlusions in the brain that cause ischemic strokes. The technology addresses many cases for which clot retrieval is not appropriate and may prevent smaller pieces of the clot from causing damage further down the vasculature.

The stent is used to bore through the clot, creating a passage for a narrow stream of blood to flow through. Special nanoparticles carrying clot busting drugs are then released toward the clot. Designed to let go of their payloads when put under high pressure, the nanoparticles only become active when passing through the freshly made tunnel within the clot. Since the drug is released just near the clot, it sticks to it and dissolves it. Any pieces of the clot breaking away should also get a few of the millions of nanoparticles passing through attached to them, helping to break up any loose bits that may otherwise cause further damage.

 

ekso-stimulationParalyzed People Walk Again!

Last year we've seen real progress toward getting paralyzed folks back up on their feet again, and not by simply using exoskeletons. At UCLA researchers managed to non-invasively stimulate the spinal cords of paralyzed men who were then able to voluntarily move their legs. Though they weren't exactly walking and remained horizontal, one man out of the study went on with specialized rehab to be able to use a smart exoskeleton.

The UCLA researchers combined non-invasive spinal cord stimulation from NeuroRecovery Technologies with a powered exoskeleton from EKSO Bionics. The combination allowed the man to actually walk again, using his legs to push forward and take repeated steps while being supported by the exoskeleton.

Coincidentally, last year we got a chance to visit EKSO's research lab and try out an exoskeleton for ourselves. Though the new prototype device we tried was designed for able bodied people operating heavy handheld equipment, the trip allowed us to experience the potential of exoskeletons for medical applications.

 

 

XstatXStat

Can the same device make it to our "Best Of" list two years in a row? If it's the XStat Rapid Hemostasis System, indeed it can. While originally developed for battlefield medics to stop bleeding from gunshot wounds, only this month has it been approved by the FDA for civilian use.

The XStat is a syringe filled with tablets made of an absorbent material. It's inserted into the wound and the sponge tablets that are pushed inside rapidly swell on contact with blood. Since their new volume is many times their original size, the soaked sponges end up filling the space of the wound, preventing further bleeding. Once the patient is delivered to the hospital and treated, X-rays can be used to make sure all the sponges are removed since they all have a small radiopaque marker within them.

 

Fetal Pacemaker

fetal-pacemaker-bigWhile adult pacemakers are getting tiny, some patients may benefit considerably more from pacemaker miniaturization. Children born with complete heart block, a condition in which electrical signals don't propagate properly throughout the heart, often don't make it before a pacemaker can be implanted. Moreover, external pacemakers that are often used can come with serious side effects.

A team from Children's Hospital Los Angeles and University of Southern California built and tested a pacemaker that can be implanted in utero into a fetus. Because the procedure can be done before birth and the pacemaker fully implanted into the child, we may soon witness complete heart block turn into a considerably less grave of a condition.

The device has already been tested with great success on sheep fetuses and the team behind the new pacemaker believes it's ready for clinical trials. These should commence soon since the device is already covered by the FDA's Humanitarian Use Device designation.

 

Light Powered Cardiac Pacemaker

Since we're on the subject of pacemakers, we might be seeing the way they work fundamentally change. At Israel's Technion-Institute of Technology researchers have been able to pace the rhythm of a rat's heart using a beam of light. This was accomplished by using a virus to make the rat express the Channelrhodopsin-2 transgene within its ventricular myocardium. This made the rat heart react to blue light effectively the same as to an electric pacemaker, contracting along with flashes of the light. Since there aren't any leads and the only device needed for pacing is a simple strobe light, the optogenetic technology may one day become common. One big next step to bringing light pacemakers closer to clinical practice is to figure out the optimal places within the heart where to express the transgene.

Check out this video of a rat heart beating to the rhythm of a light:

 

Light Producing Sleep Mask for Preventing Diabetic Retinopathy

Noctura

Diabetic retinopathy is an unfortunate, but very common way for people with diabetes to lose their eyesight. It's been a difficult to manage condition, but now there's a new night-time sleep mask that may help dramatically slow its onset. As a patient's diabetes progresses, the blood circulation worsens and the supply of oxygen to the retina is compromised. retinopathyThe retina is especially oxygen-starved at night since the rods, which are used primarily when the eyes dark-adjust, demand more oxygen than the light-activated cones. In response to this ischemia, the body signals for additional blood vessels to be formed in this region, but these new blood vessels are very weak and susceptible to microaneurysms and leaking.  This leaking leads to retinal edema and eventually macular edema, which destroys a patient's eyesight.

The Noctura 400 sleep mask from PolyPhotonix prevents the patient's eyes from dark-adapting while the patient is asleep. It continuously shines light at the user's closed eyelid, but the color and brightness of this light was selected such that it prevents the rods from dark-adapting but does not stimulate the patient's cones or other photoreceptive cells.  This prevents the therapy from adversely affecting the patient's quality of sleep.

 

EarLens Laser-based Hearing Device

headerImage_deviceThis year we also saw an FDA approval of the laser-based hearing aid from EarLens Corporation. The EarLens consists of two parts: a tympanic membrane transducer, which is non-surgically placed deep into the ear canal on the eardrum, and a behind-the-ear audio processor that is connected to a probe that's placed in the ear canal. Sounds are converted to electronic signals, digitally processed, amplified, and sent to the ear tip, which contains a laser diode sending out pulses of light. A photodetector in the tympanic membrane transducer converts the light back into electronic signals, transmitting sound vibrations directly to the eardrum by direct contact. Check out how this ingenious device works:

 

WiSE Wireless Technology for LV Heart Pacing Without Coronary Sinus Leads

WiSE-technology

Pacemakers typically deliver electric signals only to the right side of the heart because that's the easy route for lead placement. Now there's a way for pacing both sides of the heart using a conventional pacemaker coupled with an additional system. The WiSE technolory from EBR Systems includes an implanted pulse generator near the heart and a receiver-electrode attached to the endocardium of the left ventricle.

The generator detects the signal of the primary pacemaker and fires off an ultrasonic pulse toward the receiver-electrode as needed. The tiny device converts sound waves into an electrical signal, pacing the left ventricle. One of the main advantages of the system is that it allows the physician to place the electrode anywhere within the heart, optimizing pacing therapy for each patient.

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And there it is, 2015 is wrapping to a close, but on a high note. We are seeing revolutionary changes in how many diseases are managed, treated, and cured, and there's a definite sense that things are only heating up. Genetic technologies, better approaches to pacing and stimulation, new materials and their applications, and many other aspects of how medicine can be improved will paint the pages of Medgadget in the coming years.

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Timing of routine infant vaccinations and risk of food allergy and eczema at one year of age

Abstract

Background

Epidemiological evidence suggests that routine vaccinations can have non-targeted effects on susceptibility to infections and allergic disease. Such effects may depend on age at vaccination, and a delay in pertussis vaccination has been linked to reduced risk of allergic disease. We aimed to test the hypothesis that delay in vaccines containing diphtheria-tetanus-acelullar pertussis (DTaP) is associated with reduced risk of food allergy and other allergic diseases.

Methods

HealthNuts is a population-based cohort in Melbourne, Australia. 12 month-old infants were skin prick tested to common food allergens, and sensitized infants were offered oral food challenges to determine food allergy status. In this data linkage study, vaccination data for children in the HealthNuts cohort were obtained from the Australian Childhood Immunisation Register. Associations were examined between age at the first dose of DTaP and allergic disease.

Results

109 of 4433 children (2.5%) received the first dose of DTaP one month late (delayed DTaP). Overall, delayed DTaP was not associated with primary outcomes of food allergy (adjusted odds ratio (aOR) 0.77; 95% CI 0.36-1.62, p=0.49) or atopic sensitization (aOR 0.66; 95% CI 0.35-1.24, p=0.19). Among secondary outcomes, delayed DTaP was associated with reduced eczema (aOR 0.57; 95% CI 0.34-0.97, p=0.04) and reduced use of eczema medication (aOR 0.45; 95% CI 0.24-0.83, p=0.01).

Conclusions

There was no overall association between delayed DTaP and food allergy, however children with delayed DTaP had less eczema and less use of eczema medication. Timing of routine infant immunizations may affect susceptibility to allergic disease.

This article is protected by copyright. All rights reserved.



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IJMS, Vol. 17, Pages 37: The Role of bFGF in the Excessive Activation of Astrocytes Is Related to the Inhibition of TLR4/NFκB Signals

Astrocytes have critical roles in immune defense, homeostasis, metabolism, and synaptic remodeling and function in the central nervous system (CNS); however, excessive activation of astrocytes with increased intermediate filaments following neuronal trauma, infection, ischemia, stroke, and neurodegenerative diseases results in a pro-inflammatory environment and promotes neuronal death. As an important neurotrophic factor, the secretion of endogenous basic fibroblast growth factor (bFGF) contributes to the protective effect of neuronal cells, but the mechanism of bFGF in reactive astrogliosis is still unclear. In this study, we demonstrated that exogenous bFGF attenuated astrocyte activation by reducing the expression of glial fibrillary acidic protein (GFAP) and other markers, including neurocan and vimentin, but not nestin and decreased the levels of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), via the regulation of the upstream toll-like receptor 4/nuclear factor κB (TLR4/NFκB) signaling pathway. Our study suggests that the function of bFGF is not only related to the neuroprotective and neurotrophic effect but also involved in the inhibition of excessive astrogliosis and glial scarring after neuronal injury.

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IJMS, Vol. 17, Pages 33: Targeted Radionuclide Therapy of Human Tumors

Targeted radionuclide therapy is one of the most intensively developing directions of nuclear medicine. Unlike conventional external beam therapy, the targeted radionuclide therapy causes less collateral damage to normal tissues and allows targeted drug delivery to a clinically diagnosed neoplastic malformations, as well as metastasized cells and cellular clusters, thus providing systemic therapy of cancer. The methods of targeted radionuclide therapy are based on the use of molecular carriers of radionuclides with high affinity to antigens on the surface of tumor cells. The potential of targeted radionuclide therapy has markedly grown nowadays due to the expanded knowledge base in cancer biology, bioengineering, and radiochemistry. In this review, progress in the radionuclide therapy of hematological malignancies and approaches for treatment of solid tumors is addressed.

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IJMS, Vol. 17, Pages 25: Interleukin-10 Protection against Lipopolysaccharide-Induced Neuro-Inflammation and Neurotoxicity in Ventral Mesencephalic Cultures

Interleukin (IL)-10, an anti-inflammatory cytokine, is expressed in the brain and can inhibit microglial activation. Herein, we utilized lipopolysaccharide (LPS)-induced inflammatory Parkinson's disease (PD) cell model to determine whether microglia and astrocytes are necessary targets for IL-10 neuroprotection. Primary ventral mesencephalic (VM) cultures with different composition of neurons, microglia and astrocytes were prepared. The cells were exposed to IL-10 (15, 50 or 150 ng/mL) 1 h prior to LPS (50 ng/mL) treatment. LPS induced dopaminergic and non-dopaminergic neuronal loss in VM cultures, VM neuron-enriched cultures, and neuron-microglia co-cultures, but not in neuron-astrocyte co-cultures. IL-10 reduced LPS-induced neuronal loss particularly in single VM neuron cultures. Pro-inflammatory mediators (TNF-α, IL-1β, inducible nitric oxide synthase and cyclooxygenase-2) were upregulated in both neuron-microglia and neuron-astrocyte co-cultures by LPS. In contrast, neurotrophic factors (brain-derived neurotrophic factor, insulin-like growth factor-1 or glial cell-derived neurotrophic factor) were downregulated in neuron-microglia co-cultures, but upregulated in neuron-astrocyte co-cultures by LPS. IL-10 reduced both the increase in production of the pro-inflammatory mediators and the decrease in production of the neurotrophic factors induced by LPS. These results suggest that astrocytes can balance LPS neurotoxicity by releasing more neurotrophic factors and that IL-10 exerts neuroprotective property by an extensive action including direct on neurons and indirect via inhibiting microglial activation.

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