Conditioned pain modulation in temporomandibular disorders (TMD) pain patients

The aims were to investigate (1) if temporomandibular disorders (TMD) patients with temporomandibular joint (TMJ) pain had different conditioned pain modulation (CPM) compared with healthy subjects and, (2) if clinical pain characteristics influenced CPM. Sixteen TMD pain patients and 16 age-matched healthy subjects were participated. A mechanical conditioning stimulus (CS) was applied to pericranial muscles provoking a pain intensity of 5/10 on a visual analogue scale. Pressure pain thresholds (PPT) and pressure pain tolerance thresholds (PPTol) were assessed at masseter, forearm and painful TMJ (only PPT) before, during, and 20 min after CS. Data were analyzed with ANOVAs. The correlations between CPM effect and ratings of TMD pain intensity on a numerical rating scale (NRS) or the pain duration were calculated (correlation coefficient; R). The relative PPT and PPTol increases (mean for the three assessment sites) during CS were significantly higher than baseline in healthy subjects (43.0 ± 3.6, 33.0 ± 4.0 %; P < 0.001, P < 0.001) but not in the TMD pain patients (4.9 ± 2.7, ?1.4 ± 4.1 %; P = 0.492, P = 1.000) with significant differences between groups (P < 0.001). In the patients, the relative PPT changes during CS were not significantly higher than baseline at TMJ (5.3 ± 3.8 %, P = 0.981) and masseter (?2.8 ± 4.8 %, P = 1.000) but significantly higher at forearm (12.3 ± 4.7 %, P = 0.039). No correlation was detected between TMD pain intensity and CPM effect (R = ?0.261; P = 0.337) or between pain duration and CPM effect (R = ?0.423; P = 0.103) at painful TMJ. These findings indicate that CPM is impaired in TMD pain patients especially at sites with chronic pain but not at pain-free sites and that the clinical pain characteristics do not influence CPM.     

A retrospective comparative study of mandibular fracture treatment with internal fixation using reconstruction plate versus miniplates

PurposeThis study compared the clinical success rates of mandibular fracture treatment using reconstruction plates or miniplates and clarified the selection criteria for reconstruction plates.MethodsAll patients who had surgically-treated mandible fractures from 2008 to 2017 with sufficient follow-up were retrospectively analyzed for information about the fracture condition, treatment, and outcomes.ResultsA total of 126 surgically-treated mandible fractures without mandibular condylar fracture in 105 patients (76 male, 29 female) were included. Reconstruction plates were used in 32 fractures with very good postoperative occlusal function. Four cases with complications requiring reoperation were treated using only miniplates. Variables that were statistically associated with follow-up surgery included simple versus comminuted mandible fracture, and the absence of teeth that could be used for intermaxillary fixation (P < 0.05). In the miniplates treatment for comminuted fracture, there was a significant difference in the treatment outcome depending on the number of free bone-fragments and the presence of bone-fragments requiring removal within 1 cm (P < 0.05).ConclusionReconstruction plates provided better treatment outcomes for comminuted fractures and fractures without teeth. Selecting a reconstruction plate that is capable of sufficiently overloading is important in comminuted fractures with multiple free bone-fragments and bone-fragments requiring removal.     

Loss of heterozygosity in 7q myeloid disorders: clinical associations and genomic pathogenesis

Loss of heterozygosity affecting chromosome 7q is common in acute myeloid leukemia and myelodysplastic syndromes, pointing toward the essential role of this region in disease phenotype and clonal evolution. The higher resolution offered by recently developed genomic platforms may be used to establish more precise clinical correlations and identify specific target genes. We analyzed a series of patients with myeloid disorders using recent genomic technologies (1458 by single-nucleotide polymorphism arrays [SNP-A], 226 by next-generation sequencing, and 183 by expression microarrays). Using SNP-A, we identified chromosome 7q loss of heterozygosity segments in 161 of 1458 patients (11%); 26% of chronic myelomonocytic leukemia patients harbored 7q uniparental disomy, of which 41% had a homozygous EZH2 mutation. In addition, we describe an SNP-A-isolated deletion 7 hypocellular myelodysplastic syndrome subset, with a high rate of progression. Using direct and parallel sequencing, we found no recurrent mutations in typically large deletion 7q and monosomy 7 patients. In contrast, we detected a markedly decreased expression of genes included in our SNP-A defined minimally deleted regions. Although a 2-hit model is present in most patients with 7q uniparental disomy and a myeloproliferative phenotype, haplodeficient expression of defined regions of 7q may underlie pathogenesis in patients with deletions and predominant dysplastic features.     

Association of gene expression involving innate immunity and genetic variation in interleukin 28B with antiviral response

Innate immunity plays an important role in host antiviral response to hepatitis C viral (HCV) infection. Recently, single nucleotide polymorphisms (SNPs) of IL28B and host response to peginterferon α (PEG-IFNα) and ribavirin (RBV) were shown to be strongly associated. We aimed to determine the gene expression involving innate immunity in IL28B genotypes and elucidate its relation to response to antiviral treatment. We genotyped IL28B SNPs (rs8099917 and rs12979860) in 88 chronic hepatitis C patients treated with PEG-IFNα-2b/RBV and quantified expressions of viral sensors (RIG-I, MDA5, and LGP2), adaptor molecule (IPS-1), related ubiquitin E3-ligase (RNF125), modulators (ISG15 and USP18), and IL28 (IFNλ). Both IL28B SNPs were 100% identical; 54 patients possessed rs8099917 TT/rs12979860 CC (IL28B major patients) and 34 possessed rs8099917 TG/rs12979860 CT (IL28B minor patients). Hepatic expressions of viral sensors and modulators in IL28B minor patients were significantly up-regulated compared with that in IL28B major patients (≈ 3.3-fold, P < 0.001). However, expression of IPS-1 was significantly lower in IL28B minor patients (1.2-fold, P = 0.028). Expressions of viral sensors and modulators were significantly higher in nonvirological responders (NVR) than that in others despite stratification by IL28B genotype (≈ 2.6-fold, P < 0.001). Multivariate and ROC analyses indicated that higher RIG-I and ISG15 expressions and RIG-I/IPS-1 expression ratio were independent factors for NVR. IPS-1 down-regulation in IL28B minor patients was confirmed by western blotting, and the extent of IPS-1 protein cleavage was associated with the variable treatment response. CONCLUSION: Gene expression involving innate immunity is strongly associated with IL28B genotype and response to PEG-IFNα/RBV. Both IL28B minor allele and higher RIG-I and ISG15 expressions and RIG-I/IPS-1 ratio are independent factors for NVR.     

Pure topographical disorientation in novel environments without anterograde amnesia: a case study

ABSTRACT

Topographical disorientation (TD) in novel environments is considered to be a part of anterograde amnesia. A 56-year-old woman presented with pure TD only in novel environments following limbic encephalitis. She could not remember directions inside the hospital on weekly outpatient visits; however, her verbal and visual anterograde memories were normal. In the test of learning photographs of scenes, faces, and objects, only her scores for landscapes were worse than those in healthy controls. These findings suggested that her TD specific to landscapes and directions in novel environments was caused by category-specific memory impairment related to bilateral hippocampal and parahippocampal dysfunction.     

Molecular analysis of afibrinogenemic mutations caused by a homozygous FGA1238?bp deletion, and a compound heterozygous FGA1238?bp deletion and novel FGA c.54+3A>C substitution

We identified two afibrinogenemic girls in two Japanese families and performed molecular analysis to clarify the mechanisms of fibrinogen defects. Genetic analyses were performed by PCR amplification of the fibrinogen gene and DNA sequence analysis. To analyze the mechanisms of mature fibrinogen defects in plasma, we cloned minigenes from the proposita's PCR-amplified DNA, transfected them into CHO cells, and sequenced the cDNA amplified with the RT reaction followed by PCR. Sequence analyses indicated that one was caused by a homozygous 1238?bp deletion of the fibrinogen Aα-chain gene (FGAΔ1238) and the other was a compound heterozygous FGAΔ1238 and novel FGA c.54+3A>C substitution. The minigene corresponding to FGAΔ1238 generates two aberrant mRNAs, both of which may induce a frameshift and terminate prematurely. In contrast, the minigene corresponding to FGA c.54+3A>C generates two aberrant mRNAs, one of which may induce a frameshift and terminate prematurely, and the other uses a cryptic 5' splice site in exon 1, resulting in the deletion of six amino acids in signal peptides. Molecular analyses of both genetic variants suggest that the lack of a mature Aα-chain, impaired assembly, and/or secretion of the fibrinogen molecule may lead to afibrinogenemia.