Project description:Purpose:Lumbar transforaminal selective nerve root injection (SNRI) is effective for controlling radicular pain. However, when a patient occasionally experiences severe foraminal stenosis, osteophytes cover the outside opening of the neural foramen, preventing clinicians from inserting a needle tip within the neural foramen. Patients and Methods:An 81-year-old man complained of left L5 radicular pain (left thigh and calf) due to severe left L5-S1 foraminal stenosis. After failure of conventional transforaminal SNRI in the left L5 due to severe degenerative change in the lumbar spine, SNRI was performed using a Racz catheter. After inserting a 16-gauge cannula via the sacral hiatus, the Racz catheter was inserted. The tip of the catheter was positioned near the left L5 nerve root. After confirming the location of the needle tip using a contrast dye, 20 mg (40 mg/mL) of triamcinolone with 0.5 mL of 1% lidocaine and 2 mL of normal saline was injected. Results:Immediately after the procedure, the patient's pain completely disappeared. During the 1- and 2-month follow-ups, the patient reported only slight pain in the thigh and calf. Conclusion:When it is not possible to perform a conventional transforaminal SNRI, SNRI using a Racz catheter can be an effective treatment option for controlling lumbar radicular pain.
Project description:One possible consequence of dentoalveolar trauma is the development of external inflammatory root resorption (EIRR), which represents an anatomic and microbiologic challenge for clinicians. This case report describes different strategies implemented for successful endodontic management of teeth with multiple EIRR lesions, highlighting the orthograde root canal filling using a tricalcium silicate-based material (Biodentine, Septodont, Saint-Maur-des-Fossés, France). A 17-year-old female patient presented with severe pain in the anterior maxillary teeth and a history of trauma. Two- and three-dimensional radiographic exams confirmed EIRR in three teeth, with a total of 11 EIRR lesions, three exhibiting communication with the root canal. Therefore, chemo-mechanical preparation complemented by ultrasonic activation of irrigants and some changes of intra-canal dressing with calcium hydroxide were performed to reduce the microbiologic load of the affected teeth as much as possible. Then, the canals were entirely filled with Biodentine to interrupt the root resorption process and strengthen the remaining root structure. A 60-month follow-up showed the disappearance of bone rarefactions and the complete repair of the 11 EIRR lesions. The favorable long-term response indicates the feasibility of using tricalcium silicate-based putty as part of orthograde endodontic treatment of teeth with EIRR and root perforations.
Project description:The cyclic GMP-dependent protein kinase (PKG) of apicomplexan parasites is essential for secretion of micronemes and host cell invasion and egress. Both kinase specificity and localization can determine which substrates are phosphorylated. The functions of plasma membrane and cytosolic PKG isoforms of Toxoplasma gondii were unknown because of difficulties precisely manipulating expression of essential genes. Brown et al. (K. M. Brown, S. Long, and L. D. Sibley, mBio 8:e00375-17, https://doi.org/10.1128/mBio.00375-17) adapted the auxin-inducible degron (AID) system for conditional expression of T. gondii proteins. AID, in combination with clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 gene editing, facilitated creation of a panel of PKG mutants to demonstrate that the membrane association via acylation of PKG is critical for its essential functions in tachyzoites. The cytosolic form of PKG is not sufficient for viability and is dispensable. These studies illuminate a critical role for targeting of kinase complexes for parasite viability. The AID system enables rapid, conditional regulation of protein expression that expands the molecular toolbox of T. gondii.
Project description:Objectives:To investigate the success rate of supplemental intraseptal and buccal infiltration anaesthesia in mandibular molars undergoing endodontic therapy/extraction when the inferior alveolar nerve block has failed. Material and Methods:A prospective clinical trial including 200 patients undergoing lower molar root canal treatment/teeth extraction was conducted. Only 80 patients of the participants who had profound lower lip anaesthesia after the administration of inferior alveolar nerve block (IANB) were in pain within treatment. Patients experiencing moderate to severe pain upon using elevators, forceps, bur, or endodontic file were randomly allocated to the 2% lidocaine intraseptal injection and 4% articaine buccal infiltration groups. Level of pain was assessed every 2 to 10 min on standard 100 mm visual analogue scales. Results:Overall, 55 (69%) of patients who were given either intraseptal injection of 2% lidocaine or buccal infiltration of 4% articaine had successful anaesthesia of lower molar teeth within 10 min. However, 25 (31%) of participating patients in the buccal infiltration and the intraseptal groups had failed anaesthesia within the study duration (10 min), and they received additional local anaesthetic. IANBs were more painful than buccal and intraseptal injections. However, buccal articaine injections were significantly more comfortable than intraseptal lidocaine injections (P > 0.001). Conclusions:Supplemental intraseptal injection of 2% lidocaine and buccal infiltration of 4% articaine achieved profound pulpal anaesthesia in 69% of patients when the inferior alveolar nerve block failed. Recommendations can be given to dental practitioners to use infiltration of 4% articaine in conjunction with intraseptal injection of 2% lidocaine to anaesthetize the lower molar teeth when inferior alveolar nerve block fails.
Project description:As the field of neuroimaging grows, it can be difficult for scientists within the field to gain and maintain a detailed understanding of its ever-changing landscape. While collaboration and citation networks highlight important contributions within the field, the roles of and relations among specific areas of study can remain quite opaque. Here, we apply techniques from network science to map the landscape of neuroimaging research documented in the journal NeuroImage over the past decade. We create a network in which nodes represent research topics, and edges give the degree to which these topics tend to be covered in tandem. The network displays small-world architecture, with communities characterized by common imaging modalities and medical applications, and with hubs that integrate these distinct subfields. Using node-level analysis, we quantify the structural roles of individual topics within the neuroimaging landscape, and find high levels of clustering within the structural MRI subfield as well as increasing participation among topics related to psychiatry. The overall prevalence of a topic is unrelated to the prevalence of its neighbors, but the degree to which a topic becomes more or less popular over time is strongly related to changes in the prevalence of its neighbors. Finally, we incorporate data from PNAS to investigate whether it serves as a trend-setter for topics' use within NeuroImage. We find that popularity trends are correlated across the two journals, and that changes in popularity tend to occur earlier within PNAS among growing topics. Broadly, this work presents a cohesive model for understanding the emergent relationships and dynamics of research topics within NeuroImage.
Project description:The proteins belonging to the inhibitor of growth (ING) family of proteins serve as epigenetic readers of the H3K4Me3 histone mark of active gene transcription and target histone acetyltransferase (HAT) or histone deacetylase (HDAC) protein complexes, in order to alter local chromatin structure. These multidomain adaptor proteins interact with numerous other proteins to facilitate their localization and the regulation of numerous biochemical pathways that impinge upon biological functions. Knockout of some of the ING genes in murine models by various groups has verified their status as tumor suppressors, with ING1 knockout resulting in the formation of large clear-cell B-lymphomas and ING2 knockout increasing the frequency of ameloblastomas, among other phenotypic effects. ING4 knockout strongly affects innate immunity and angiogenesis, and INGs1, ING2, and ING4 have been reported to affect apoptosis in different cellular models. Although ING3 and ING5 knockouts have yet to be published, preliminary reports indicate that ING3 knockout results in embryonic lethality and that ING5 knockout may have postpartum effects on stem cell maintenance. In this review, we compile the known information on the domains of the INGs and the effects of altering ING protein expression, to better understand the functions of this adaptor protein family and its possible uses for targeted cancer therapy.
Project description:Self-assembly of fluorenylmethoxycarbonyl-protected diphenylalanine (FmocFF) in water is widely known to produce hydrogels. Typically, confocal microscopy is used to visualize such hydrogels under wet conditions, that is, without freezing or drying. However, key aspects of hydrogels like fiber diameter, network morphology and mesh size are sub-diffraction limited features and cannot be visualized effectively using this approach. In this work, we show that it is possible to image FmocFF hydrogels by Points Accumulation for Imaging in Nanoscale Topography (PAINT) in native conditions and without direct gel labelling. We demonstrate that the fiber network can be visualized with improved resolution (≈50 nm) both in 2D and 3D. Quantitative information is extracted such as mesh size and fiber diameter. This method can complement the existing characterization tools for hydrogels and provide useful information supporting the design of new materials.
Project description:In this issue of Cell, Ma et al. reveal a mechanistic role for PIEZO1 in iron homeostasis through molecular genetic mouse studies. They also demonstrate implications for human iron overload and deficiency syndromes, susceptibility to malarial infection, and red blood cell turnover in persons of African ancestries.
Project description:Immune cell recognition of bacterial products usually occurs via specific pattern recognition receptors, but new research recently published in Cell by Wolf et al. (2016) demonstrates that the glycolytic enzyme hexokinase can act as an innate immune sensor by binding to bacterial derived N-acetylglucosamine (NAG).
Project description:Background Identification of patients at risk of tuberculosis relapse following treatment would revolutionize clinical trials of new drugs and regimens and facilitate clinical management. The study aim was to determine whether tuberculosis patients who subsequently suffer relapse have different immune responses to mycobacteria in vitro compared to patients who remain cured for two years post-treatment. Methods First episode pulmonary tuberculosis patients were recruited into a surrogate marker study in Cape Town, South Africa. Peripheral blood samples were collected at diagnosis and after two and four weeks of tuberculosis treatment. Diluted blood was cultured with live Mycobacterium tuberculosis for six days and cellular RNA was frozen. Gene expression in samples from ten patients who subsequently relapsed, confirmed by stain genotyping, was compared to those who remained cured using Affymetrix microarrays. Results At diagnosis, the expression of 668 genes was significantly different in samples from patients who subsequently relapsed compared to successfully cured patients, and these differences persisted for at least four weeks. Gene Ontology and biological pathways analyses revealed the most significant difference was up-regulation of genes involved in cytotoxic cell-mediated killing, such as perforin, granulysin and fas ligand. Results were confirmed by qRT-PCR in a wider patient cohort. Conclusions These data show that patients who will subsequently relapse exhibit altered immune responses at diagnosis, including excessively robust cytolytic responses to M. tuberculosis in vitro, compared to patients who will achieve durable cure. Together with microbiological and clinical indices, these differences could be exploited for patient stratification in drugs trials, or for host-directed therapy development.