The mechanism of pain in dentine hypersensitivity is poorly understood but proposed to result from the activation of dental sensory neurons in response to dentinal fluid movements. Odontoblasts have ...been suggested to contribute to thermal and mechanosensation in the tooth via expression of transient receptor potential (TRP) channels. However, a mechanism by which odontoblasts could modulate neuronal activity has not been demonstrated. In this study, we investigated functional TRP channel expression in human odontoblast-like cells and measured ATP release in response to TRP channel activation. Human immortalized dental pulp cells were driven toward an odontoblast phenotype by culture in conditioned media. Functional expression of TRP channels was determined with reverse transcription polymerase chain reaction and ratiometric calcium imaging with Fura-2. ATP release was measured using a luciferin-luciferase assay. Expression of mRNA for TRPA1, TRPV1, and TRPV4 but not TRPM8 was detected in odontoblasts by reverse transcription polymerase chain reaction. Expression of TRPV4 protein was detected by Western blotting and immunocytochemistry. The TRPA1 agonists allyl isothiocyanate and cinnamaldehyde and the TRPV4 agonist GSK1016790A caused a concentration-dependent increase in intracellular Ca2+ concentration that was inhibited by the selective antagonists HC030031, AP18, and HC067047, respectively. In contrast, exposure to the TRPV1 agonist capsaicin or the TRPM8 agonist icilin had no effect on intracellular Ca2+ concentration. Treatment with allyl isothiocyanate, cinnamaldehyde, or GSK1016790A caused an increase in ATP concentration in culture medium that was abolished by preincubation with TRP channel antagonists. These data demonstrate that activation of TRPA1 and TRPV4 channels in human odontoblast-like cells can stimulate ATP release. We were unable to confirm the presence of thermosensitive TRPV1 and TRPM8 that has previously been reported in odontoblasts.
The safety and efficacy of edoxaban and dalteparin is unclear for several cancer groups.
We evaluated the occurrence of the primary outcome in large cancer groups. The primary outcome was the ...composite of recurrent VTE or major bleeding over 12 months.
In patients with gastrointestinal cancer, the primary outcome occurred in 19.4% patients given edoxaban and in 15.0% given dalteparin (risk difference RD, 4.4%; 95%-CI, −4.1% to 12.8%). The corresponding rates for edoxaban and dalteparin were 10.4% and 10.7% for lung cancer (RD, −0.3%; 95%-CI, −10.0% to 9.5%), 13.6% and 12.5% for urogenital cancer (RD, 1.1; 95%-CI, −10.1–12.4), 3.1% and 11.7% for breast cancer (RD, −8.6; 95%-CI, −19.3–2.2), 8.9% and 10.9% for hematological malignancies (RD, −2.0; 95%-CI, −13.1–9.1), and 10.4% and 17.4% for gynecological cancer (RD, −7.0; 95%-CI, −19.8–5.7). In the subgroup of gastrointestinal cancer, edoxaban was associated with a 3.5% lower absolute risk of recurrent VTE and a 7.9% higher risk of major bleeding.
Edoxaban has a similar risk-benefit ratio to dalteparin in most cancer groups. In those with gastrointestinal cancer, the lower risk of recurrent VTE and the advantages of oral therapy need to be balanced against the increased risk of major bleeding.
•The Hokusai VTE Cancer Study was a randomized controlled trial for cancer patients.•It randomized patients to either edoxaban or dalteparin for the treatment of VTE.•This analysis provides adjudicated study outcomes for all large cancer groups.•In most cancers, the primary outcome was comparable between both regimens.•The major bleeding risk in gastrointestinal cancer is higher in edoxaban recipients.
BackgroundRefugees have different experiences of obtaining a refugee status, however it remains unclear if this affects their risk of psychiatric disorders. The aim of this study was to investigate ...whether risk for non-affective psychotic disorder (NAPD) and post-traumatic stress disorder (PTSD) differs between quota refugees (resettled from refugee camps) and non-quota refugees (former asylum seekers).MethodA register-based cohort with a sample size of 52 561 refugees in Sweden starting 1 January 1997 ending 31 December 2011. Exposure: refugee status (quota or non-quota refugees). Cox regression models estimated adjusted HRs with 95% CIs for NAPD (International Classification of Diseases, Tenth Revision (ICD-10), F20–29) and PTSD (ICD-10, F43.1) by refugee status.ResultsThere were more non-quota refugees (77.0%) than quota refugees (23.0%). In total we identified 401 cases of NAPD, 1.0% among quota refugees and 0.7% among non-quota refugees, and 1070 cases of PTSD, 1.9% among quota refugees and 2.1% among non-quota refugees. Male quota refugees were at increased risk for NAPD compared with male non-quota refugees (HRmale=1.41, 95% CI 1.09 to 1.82 and HRfemale=0.65, 95% CI 0.42 to 1.00). All quota refugees were at a reduced risk of PTSD compared with non-quota refugees (HR=0.74, 95% CI 0.64 to 0.87).ConclusionsThis study suggests that risk of NAPD and PTSD varies for quota and non-quota refugees, highlighting the possibility that different experiences of the migration process differentiate the risk of psychiatric disorders among refugees.
Culture-based isolation and enumeration of bacterial human pathogens from environmental and human food samples has significant limitations. Many pathogens enter a viable but non-culturable (VBNC) ...state in response to stress, and cannot be detected via culturing methods. Favourable growth conditions with a source of energy and an ideal stoichiometric ratio of carbon to inorganic elements can reverse this VBNC state. This review will focus on the bacterium Campylobacter jejuni which is a leading cause of food borne illness in the developed world. C. jejuni can enter a VBNC state in response to extremes in: pH, moisture content, temperature, nutrient content and salinity. Once in a VBNC state, the organism must maintain an energy balance from substrate oxidation through respiration to grow, divide and remain viable. The goal of this review is a greater understanding of how abiotic stress and thermodynamics influence the viability of C. jejuni.
ABO incompatibility has been considered as an important immunological barrier for renal transplantation. With the advent of effective preconditioning protocols, it is now possible to do renal ...transplants across ABO barrier. We hereby present a single center retrospective analysis of all consecutive ABOi renal transplants performed from November 2011 to August 2014. Preconditioning protocol consisted of rituximab, plasmapheresis and intravenous immunoglobulin (IVIG) and maintenance immunosuppression consisted of tacrolimus, mycophenolate sodium, and prednisolone. The outcome of these ABOi transplants was compared with all other consecutive ABO-compatible (ABOc) renal transplants performed during same time. Twenty ABOi renal transplants were performed during the study period. Anti-blood group antibody titer varied from 1:2 to 1:512. Patient and graft survival was comparable between ABOi and ABOc groups. Biopsy proven acute rejection rate was 15% in ABOi group, which was similar to ABOc group (16.29%). There were no antibody-mediated rejections in ABOi group. The infection rate was also comparable. We conclude that the short-term outcome of ABOi and ABOc transplants is comparable. ABOi transplants should be promoted in developing countries to expand the donor pool.
Host restriction factors are potent, widely expressed intracellular blocks to viral replication that are an important component of the innate immune response to viral infection. However, viruses have ...evolved mechanisms that antagonize restriction factors. Through evolutionary pressure for both host survival and virus replication, an evolutionary 'arms race' has developed that drives continuous rounds of selection for beneficial mutations in the genes encoding restriction factors and their viral antagonists. Because viruses can evolve faster than their hosts, the innate immune system of modern-day vertebrates is for the most part optimized to defend against ancient viruses, rather than newer viral threats. Thus, the evolutionary history of restriction factors might, in part, explain why humans are susceptible or resistant to the viruses present in the modern world.
Visceral leishmaniasis (VL) caused by Leishmania chagasi is endemic to northeast Brazil. A positive delayed-type hypersensitivity skin test response (DTH+) is a marker for acquired resistance to ...disease, clusters in families and may be genetically controlled. Twenty-three single nucleotide polymorphisms (SNPs) were genotyped in the cytokine 5q23.3-q31.1 region IRF1-IL5-IL13-IL4-IL9-LECT2-TGFBI in 102 families (323 DTH+; 190 DTH-; 123 VL individuals) from a VL endemic region in northeast Brazil. Data from 20 SNPs were analyzed for association with DTH+/- status and VL using family-based, stepwise conditional logistic regression analysis. Independent associations were observed between the DTH+ phenotype and markers in separate linkage disequilibrium blocks in LECT2 (OR 2.25; P=0.005; 95% CI=1.28-3.97) and TGFBI (OR 1.94; P=0.003; 95% CI=1.24-3.03). VL child/parent trios gave no evidence of association, but the DTH- phenotype was associated with SNP rs2070874 at IL4 (OR 3.14; P=0.006; 95% CI=1.38-7.14), and SNP rs30740 between LECT2 and TGFBI (OR 3.00; P=0.042; 95% CI=1.04-8.65). These results indicate several genes in the immune response gene cluster at 5q23.3-q31.1 influence outcomes of L. chagasi infection in this region of Brazil.
To investigate the distribution of individual tooth impaction in general dental patients of Northern India.
Centre for Dental Education and Research, All India Institute of Medical Sciences, New ...Delhi.
Hospital based crossectional study.
General dental patients were examined clinically and impacted teeth were diagnosed from radiographs. The distribution of impacted teeth (excluding third molars) with respect to the arch, side and gender were recorded. The results were analyzed with respect to the prevalence of individual tooth impaction. The distribution of teeth impaction was evaluated by using the Chi-square test. A p-value of < 0.05 was considered as statistically significant.
Of 27,529 general dental patients examined, 134 (0.49%) had at least one-impacted tooth and a total of 220 impacted teeth were recorded. The most frequently impacted teeth were maxillary canines (52.27%) and the least frequently impacted teeth were maxillary first and second molars (0%).
The prevalence of teeth impaction in the North Indian dental patients was less when compared with the other populations. The most frequently impacted teeth were maxillary canines and the least frequently impacted teeth were maxillary first and second molars.
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