The effect of increasing strut porosity on the osteoinductive ability of silicate substituted calcium phosphate (SiCaP) biomaterials was investigated in an ectopic ovine model. Implants with strut ...porosities of 22.5%, 32.0% and 46.0% were inserted into the parapsinalis muscle. At 8, 12 and 24weeks histological sections were prepared. Sections were examined using backscattered scanning electron microscopy and un-decalcified histology. Bone area, implant area and bone-implant contact were quantified. At 8weeks there was no significant difference between the groups in terms of bone area and implant area. However at 12weeks, the amount of bone formation observed was significantly greater in SiCaP-46 (6.17±1.51%) when compared with SiCaP-22.5 (1.33±0.84%) p=0.035. Results also showed significantly increased amounts of bone-implant contact to the SiCaP-46 scaffold (3.30±1.17%) compared with SiCaP-22.5 (0.67±0.52%, p=0.043) at 8weeks and 12weeks; (SiCaP-46 (21.82±5.59%) vs SiCaP-22.5 (3.06±1.89%), p=0.012). At 24weeks, bone formation and graft resorption had significantly increased in all groups so that the level of bone formation in the SiCaP-46 group had increased 75-fold to 30.05±8.38%. Bone formation was observed in pores <10μm. Results suggest that bone graft substitute materials with greater strut porosity are more osteoinductive.
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson disease (PD). LRRK2 contains an "enzymatic core" composed of GTPase and kinase domains that is flanked ...by leucine-rich repeat (LRR) and WD40 protein-protein interaction domains. While kinase activity and GTP-binding have both been implicated in LRRK2 neurotoxicity, the potential role of other LRRK2 domains has not been as extensively explored.
We demonstrate that LRRK2 normally exists in a dimeric complex, and that removing the WD40 domain prevents complex formation and autophosphorylation. Moreover, loss of the WD40 domain completely blocks the neurotoxicity of multiple LRRK2 PD mutations.
These findings suggest that LRRK2 dimerization and autophosphorylation may be required for the neurotoxicity of LRRK2 PD mutations and highlight a potential role for the WD40 domain in the mechanism of LRRK2-mediated cell death.
A well-behaved spin-light emitting diode (LED) composed of InGaN/GaN multiple quantum disks (MQDs), ferromagnetic contact, and Fe3O4 nanoparticles has been designed, fabricated, and characterized. ...The degree of circular polarization of electroluminescence (EL) can reach up to a high value of 10.9% at room temperature in a low magnetic field of 0.35 T, which overcomes a very low degree of spin polarization in nitride semiconductors due to the weak spin–orbit interaction. Several underlying mechanisms play significant roles simultaneously in this newly designed device for the achievement of such a high performance. Most of all, the vacancy between nanodisks can be filled by half-metal nanoparticles with suitable energy band alignment, which enables selective transfer of spin polarized electrons and holes and leads to the enhanced output spin polarization of LED. Unlike previously reported mechanisms, this new process leads to a weak dependence of spin relaxation on temperature. Additionally, the internal strain in planar InGaN/GaN multiple quantum wells can be relaxed in the nanodisk formation process, which leads to the disappearance of Rashba Hamiltonian and enhances the spin relaxation time. Our approach therefore opens up a new route for the further research and development of semiconductor spintronics.
Objective: Due to global urbanization, technological advancements, and increasing convenience in daily activities, reduced energy expenditure in all aspects of life has become a major public health ...concern. A positive physical activity (PPA) intervention was developed to promote physical activity and fitness among Hong Kong families. PPA utilizes positive affective attitudes to circumvent barriers to health behavior change by helping families associate feelings of enjoyment with physical activity. Zero-Time Exercise (ZTEx) was introduced and promoted as a foot-in-the-door approach. Method: Using a community-based collaborative approach, the research team worked with social service organizations, a government department, and schools to implement a cluster randomized controlled crossover trial at a citywide scale. A total of 1,983 eligible participants from 1,467 families were recruited from all 18 districts in Hong Kong. Data were collected using structured questionnaires and physical fitness assessments at preintervention and 1-month and 3-month follow-up. Results: PPA was effective in increasing ZTEx and ZTEx with family members at 1-month and 3-month follow-up and in improving balance and endurance at 3-month follow-up. Semistructured focus groups provided further support for the intervention effectiveness and added in-depth insights into the participants' motivational, interpersonal, and affective experiences. Conclusion: The results not only shed light on the intervention's effectiveness for physical activity and fitness but also demonstrated that the community-based collaborative approach was successful in engaging relevant stakeholders in an active and fruitful partnership with effective capacity building for program development.
Movies vary widely in appeal, star power, cost, and other elements, and therefore, each might be expected to charge a different price. Multiplexes, however, typically charge the same price for all ...movies, except for such premium formats as 3D, a choice that has puzzled managers and researchers. Because of data limitations, minimal empirical work has directly addressed this issue. In Hong Kong, however, prices vary both within and across multiplexes. Using daily ticket prices and attendance by theater and movie, the authors empirically examine the potential gains from differentiated movie-specific pricing as well as the increasingly common two-tier (2D/3D) uniform pricing, as compared with a full uniform pricing strategy in which a theater charges the same price for all its movies. Their results show that differential pricing leads to higher profits than the two-tier uniform pricing practice, but that the improvement is limited. In contrast, the gains are substantial when compared with the full uniform pricing strategy, suggesting that only minimal differentiation (2D/3D) may obtain most of the gains available from fully differentiated prices.
BACKGROUND AND PURPOSE
Capsaicin, an agonist of transient receptor potential vanilloid 1 (TRPV1) channels, is pro‐nociceptive in the periphery but is anti‐nociceptive when administered into the ...ventrolateral periaqueductal gray (vlPAG), a midbrain region for initiating descending pain inhibition. Here, we investigated how activation of TRPV1 channels in the vlPAG leads to anti‐nociception.
EXPERIMENTAL APPROACH
We examined synaptic transmission and neuronal activity using whole‐cell recordings in vlPAG slices in vitro and hot‐plate nociceptive responses in rats after drug microinjection into the vlPAG in vivo.
KEY RESULTS
Capsaicin (1–10 µM) depressed evoked GABAergic inhibitory postsynaptic currents (eIPSCs) in vlPAG slices presynaptically, while increasing miniature excitatory PSC frequency. Capsaicin‐induced eIPSC depression was antagonized by cannabinoid CB1 and metabotropic glutamate (mGlu5) receptor antagonists, and prevented by inhibiting diacylglycerol lipase (DAGL), which converts DAG into 2‐arachidonoylglycerol (2‐AG), an endocannabinoid. Capsaicin induced membrane depolarization in 2/3 neurons recorded but, overall, increased neuronal firings by increasing evoked postsynaptic potentials. Intra‐vlPAG capsaicin reduced hot‐plate responses in rats, effects blocked by CB1 and mGlu receptor antagonists. Effects of capsaicin were antagonized by SB 366791, a TRPV1 channel antagonist.
CONCLUSIONS AND IMPLICATIONS
Capsaicin activated TRPV1s on glutamatergic terminals to release glutamate which activated postsynaptic mGlu5 receptors, yielding 2‐AG from DAG by DAGL hydrolysis. 2‐AG induces retrograde inhibition (disinhibition) of GABA release via presynaptic CB1 receptors. This disinhibition in the vlPAG leads to anti‐nociception by activating the descending pain inhibitory pathway. This is a novel TRPV1 channel‐mediated anti‐nociceptive mechanism in the brain and a new interaction between vanilloid and endocannabinoid systems.
Proton radiotherapy has been increasingly utilized to treat pediatric brain tumors, however, limited information exists regarding radiation necrosis among these patients. Our aim was to evaluate the ...incidence, timing, clinical significance, risk factors, and imaging patterns of radiation necrosis in pediatric patients with brain tumors treated with proton radiation therapy.
A retrospective study was performed on 60 consecutive pediatric patients with primary brain tumors treated with proton radiation therapy. Radiation necrosis was assessed by examining serial MRIs and clinical records to determine the incidence, timing, risk factors, imaging patterns, and clinical significance associated with the development of radiation necrosis in these patients. Radiation necrosis was defined as areas of new enhancement within an anatomic region with previous exposure to proton beam therapy with subsequent decrease on follow-up imaging without changes in chemotherapy.
Thirty-one percent of patients developed radiation necrosis with a median time to development of 5.0 months (range, 3-11 months). Risk factors included multiple chemotherapy agents (>3 cytotoxic agents) and atypical teratoid rhabdoid tumor pathology (P = .03 and P = .03, respectively). The most common imaging patterns were small (median, 0.9 cm) and multifocal (63% of patients) areas of parenchymal enhancement remote from the surgical site. The median time to complete resolution on imaging was 5.3 months (range, 3-12 months). Among patients with imaging findings of radiation necrosis, 25% demonstrated severe symptoms with medical intervention indicated.
Pediatric patients with brain tumors treated with proton radiation therapy demonstrate a high incidence of radiation necrosis and a short time to development of necrosis. Multiple small areas of necrosis are frequently identified on imaging. Exposure to multiple chemotherapy agents was a significant risk factor associated with radiation necrosis in these patients.
Organised hematoma (OH) in the para-nasal sinus and nasal cavity is a rare, non-neoplastic, benign disease which can be locally aggressive. In clinical practice, OH is easily misdiagnosed as ...malignancy and over-treated.
These patients with OH had a common history of malignant neoplasms post-radiotherapy, including two cases of nasopharyngeal carcinoma and one case of tonsil cancer with jaw osteosarcoma. All of the patients presented with symptoms of epistaxis and blood-tinged rhinorrhea. All of the patients received endoscopic endonasal surgery under navigation.
All of the patients had a good recovery after surgery. There's no recurrence after follow-up at 6 months. We therefore hypothesised that radiotherapy could be a cause of the OH. Although OH is uncommon and difficult to diagnose, a history of malignancy and imaging features with appropriate treatment are key.
The International Workshop on HIV Persistence during Therapy provides a forum in which HIV/AIDS researchers gather to share the latest research findings related to viral reservoirs and cure. The ...Tenth Workshop, which was attended by over 400 delegates, extended over 4 days and comprised eight sessions covering topics from the basic science of viral persistence to therapeutic approaches to HIV cure. Furthermore, satellite sessions on the first day of the Conference featuring cure research endeavours being pursued by the Bill and Melinda Gates Foundation as well as those being coordinated under the National Institutes of Health Martin Delaney Collaboratory program, provided important updates on research advances being made in these initiatives. As with previous conferences, the International Workshop on HIV Persistence during Therapy is primarily abstract-driven with only one invited talk for each of the sessions. This format, therefore, increases the number of presentations from early-stage investigators. Furthermore, presentations by Community representatives illustrated approaches to creating cure research literacy with effective messaging for the Community. The following article offers a synopsis of the meeting sessions. Due to space constraints, some presentations may have only been briefly discussed. Nevertheless, the Workshop abstracts can be found online (https://www/sciencedirect.com/journal/journal-of-virus-eradication/vol/8/suppl/S).
The basidiomycete Phanerochaete carnosa is a white-rot species that has been mainly isolated from coniferous softwood. Given the particular recalcitrance of softwoods to bioconversion, we conducted a ...comparative transcriptomic analysis of P. carnosa following growth on wood powder from one softwood (spruce; Picea glauca) and one hardwood (aspen; Populus tremuloides). P. carnosa was grown on each substrate for over one month, and mycelia were harvested at five time points for total RNA sequencing. Residual wood powder was also analyzed for total sugar and lignin composition.
Following a slightly longer lag phase of growth on spruce, radial expansion of the P. carnosa colony was similar on spruce and aspen. Consistent with this observation, the pattern of gene expression by P. carnosa on each substrate converged following the initial adaptation. On both substrates, highest transcript abundances were attributed to genes predicted to encode manganese peroxidases (MnP), along with auxiliary activities from carbohydrate-active enzyme (CAZy) families AA3 and AA5. In addition, a lytic polysaccharide monooxygenase from family AA9 was steadily expressed throughout growth on both substrates. P450 sequences from clans CPY52 and CYP64 accounted for 50% or more of the most highly expressed P450s, which were also the P450 clans that were expanded in the P. carnosa genome relative to other white-rot fungi.
The inclusion of five growth points and two wood substrates was important to revealing differences in the expression profiles of specific sequences within large glycoside hydrolase families (e.g., GH5 and GH16), and permitted co-expression analyses that identified new targets for study, including non-catalytic proteins and proteins with unknown function.
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