Recognition of peptide-MHC class I complexes by activating killer immunoglobulin-like receptors

Inhibitory receptors for MHC class I molecules increase the threshold of lymphocyte activation. Natural Killer (NK) cells express a large number of such inhibitory receptors, including the human killer Ig-like receptors (KIR). However, activating members of the KIR family have poorly defined ligands and functions. Here we describe the use of activating KIR tetramer reagents as probes to detect their ligands. Infection of cells with Epstein-Barr virus leads to expression of a detectable ligand for the activating receptor KIR2DS1. In this case, KIR2DS1 interacts with up-regulated peptide-MHC class I complexes on Epstein-Barr virus-infected cells in a transporter associated with antigen processing (TAP)-dependent manner. In tetramer-based cellular assays and direct affinity measurements, this interaction with MHC class I is facilitated by a broad spectrum of peptides. KIR2DS1 and its inhibitory homologue, KIR2DL1, share sensitivity to peptide sequence alterations at positions 7 and 8. These results fit a model in which activating and inhibitory receptors recognize the same sets of self-MHC class I molecules, differing only in their binding affinities. Importantly, KIR2DS1 is not always sufficient to trigger NK effector responses when faced with cognate ligand, consistent with fine control during NK cell activation. We discuss how our results for KIR2DS1 and parallel studies on KIR2DS2 relate to the association between activating KIR genes and susceptibility to autoimmune disorders.     

Association between diabetes and the prevalence of radiolucent periapical lesions in root-filled teeth: systematic review and meta-analysis

Introduction

The question of whether diabetes mellitus can influence the outcome of root canal treatment (RCT) remains unclear. The aim of this systematic review and meta-analysis was to analyze scientific available evidence on the association between diabetes and the presence of radiolucent periapical lesions (RPLs) in root-filled teeth (RFT).

Methods

The review question was as follows: in adult patients who had endodontically treated teeth, does the absence or presence of diabetes result in an increase in the prevalence of RPL associated to RFT? A systematic MEDLINE/PubMed, Wiley Online Database, Web of Science, and Scopus search was conducted using the following MeSH and keywords: Diabetes Mellitus OR Diabetes OR Diabetic OR Hyperglycemia, AND Endodontics, Periapical Periodontitis, Periapical Diseases, Apical Periodontitis, Periradicular Lesion, Periapical Radiolucency, Radiolucent Periapical Lesion, Root Canal Treatment, Root Canal Preparation, Root Canal Therapy, Root Filled Teeth, Endodontically Treated Teeth. Seven studies reporting data on the prevalence of RPL associated to RFT both in diabetic and control subjects were included.

Results

After the study selection, seven epidemiological studies fulfilled the inclusion criteria, representing data from 1593 root canal treatments, 1011 in non-diabetic control subjects, and 582 in diabetic patients. The calculated pooled odds ratio (OR = 1.42; 95 % CL = 1.11–1.80; p = 0.0058) indicates that diabetic patients have higher prevalence of RFT with RPLs than controls.

Conclusion

Available scientific evidence indicates that diabetes is significantly associated to higher prevalence of periapical radiolucencies in endodontically treated teeth, being an important putative pre-operative prognostic factor in RCT.

Clinical relevance

Taking into account that diabetes is the third most prevalent chronic medical condition among dental patients, endodontic providers should be aware of the relationship between the outcome of endodontic treatment and diabetes.

     

Use of trunk muscle training and neuromuscular electrical stimulation to reduce pain and disability in an older adult with chronic low back pain: A case report

Among older adults, low back pain (LBP) is common, costly, and disabling. Trunk muscle training (TMT) and neuromuscular electrical stimulation (NMES) have both been found to be effective in reducing LBP, but studies among older adults have been limited. An 83-year-old female with left-sided chronic LBP participated in a randomized controlled trial consisting of supervised TMT and NMES to the paraspinal muscles two times per week for 12 weeks. She also participated in a home exercise program. At the end of the intervention, she reported reduced LBP and LBP-related disability per the modified Oswestry disability index (i.e., 60% at baseline to 40% at 12 weeks). Her Short Physical Performance Battery summary score improved from 4/12 at baseline to 10/12 at 12 weeks, while her Timed Up and Go test improved from 17.21 to 15.20 s and her Repetitive Trunk Rotation test from 2.72 to 1.93 s/right–left rotation. This case demonstrates a positive short-term treatment response to TMT supplemented with NMES of the paraspinal muscles in an older adult with chronic LBP. A packaged intervention of TMT plus NMES may be a means of addressing not only LBP, but also impaired physical function and resultant disability.     

The Cerebellum in Children with Spina Bifida and Chiari II Malformation: Quantitative Volumetrics by Region

Few volumetric MRI studies of the entire cerebellum have been published; even less quantitative information is available in patients with hindbrain malformations, including the Chiari II malformation which is ubiquitous in patients with spina bifida meningomyelocele (SBM). In the present study, regional volumetric analyses of the cerebellum were conducted in children with SBM/Chiari II and typically developing (TD) children. Total cerebellar volume was significantly reduced in the SBM group relative to the TD group. After correcting for total cerebellum volume, and relative to the TD group, the posterior lobe was significantly reduced in SBM, the corpus medullare was not different, and the anterior lobe was significantly enlarged. Children with thoracic level lesions had smaller cerebellar volumes relative to those with lumbar/sacral lesions, who had smaller volumes compared to TD children. The reduction in cerebellar volume in the group with SBM represents not a change in linear scaling but rather a reconfiguration involving anterior lobe enlargement and posterior lobe reduction.     

Endoscopic sedation in pediatric practice

Best sedation practices for pediatric endoscopy involve the consideration of many patient factors, including age, medical history, clinical status, and anxiety level, as well as physician access to anesthesia support. A recent survey of pediatric gastroenterologists suggests that endoscopist-administered intravenous (iv) sedation and anesthesiologist-administered propofol represent common sedation regimens in children. Technical advances in ventilatory monitoring are contributing to increased patient safety for all children undergoing gastrointestinal procedures, regardless of sedation type.     

Review: Combination therapy with non-clozapine atypical antipsychotic medication: a review of current evidence

Use of combined antipsychotics for patients with treatment-resistant/refractory schizophrenia is common practice in psychiatry. The objective of this paper is to review the current literature on combining non-clozapine atypical antipsychotics as well as discussing the theoretical benefits and risks, and summarizing the implications for clinical practice.We found in cases of treatment-resistant schizophrenia, where clozapine is deemed inappropriate, combination therapy with non-clozapine atypical antipsychotics is a strategy worthy of consideration. Combinations using olanzapine with either amisulpride or risperidone--or quetiapine with risperidone--in theory act on different receptor profiles and in the limited data available have shown improvement in symptoms, been used most frequently, and on balance have more data on safety. Initial case reports suggest that aripiprazole combined with non-clozapine atypicals may worsen psychosis.The current literature, however, has significant limitations. For this reason, due to the lack of data on safety, caution is recommended. There needs to be further well-designed studies with the aim to specifically investigate the effects of combination therapy to allow the clinician to better balance the risks and benefits (both clinical and economical) of treatment.