Measuring Psychological Inflexibility of Suicidal Thoughts: The Acceptance and Action Questionnaire for Suicidal Ideation (AAQ-SI)

Cognitive Therapy and Research - Despite interest in psychological inflexibility as a marker of suicide risk, no measure of psychological inflexibility specific to SI exists. The present study...     

Estimation of phase signal change in neuronal current MRI for evoke response of tactile detection with realistic somatosensory laminar network model

Magnetic field generated by neuronal activity could alter magnetic resonance imaging (MRI) signals but detection of such signal is under debate. Previous researches proposed that magnitude signal change is below current detectable level, but phase signal change (PSC) may be measurable with current MRI systems. Optimal imaging parameters like echo time, voxel size and external field direction, could increase the probability of detection of this small signal change. We simulate a voxel of cortical column to determine effect of such parameters on PSC signal. We extended a laminar network model for somatosensory cortex to find neuronal current in each segment of pyramidal neurons (PN). 60,000 PNs of simulated network were positioned randomly in a voxel. Biot–savart law applied to calculate neuronal magnetic field and additional phase. The procedure repeated for eleven neuronal arrangements in the voxel. PSC signal variation with the echo time and voxel size was assessed. The simulated results show that PSC signal increases with echo time, especially 100/80 ms after stimulus for gradient echo/spin echo sequence. It can be up to 0.1 mrad for echo time = 175 ms and voxel size = 1.48 × 1.48 × 2.18 mm³. With echo time less than 25 ms after stimulus, it was just acquired effects of physiological noise on PSC signal. The absolute value of the signal increased with decrease of voxel size, but its components had complex variation. External field orthogonal to local surface of cortex maximizes the signal. Expected PSC signal for tactile detection in the somatosensory cortex increase with echo time and have no oscillation.     

Neutrophils Play an Important Role in Protective Immunity against Coxiella burnetii Infection

Coxiella burnetii is an obligate intracellular Gram-negative bacterium that causes the zoonotic disease Q fever. Although Q fever is mainly transmitted by aerosol infection, study of the immune responses in the lung following pulmonary C. burnetii infection is lacking. Neutrophils are considered the first immune cell to migrate into the lung and play an important role in host defense against aerosol infection with microbial pathogens. However, the role of neutrophils in the host defense against C. burnetii infection remains unclear. To determine the role of neutrophils in protective immunity against C. burnetii infection, the RB6-8C5 antibody was used to deplete neutrophils in mice before intranasal infection with C. burnetii. The results indicated that neutrophil-depleted mice developed more severe disease than their wild-type counterparts, suggesting that neutrophils play an important role in host defense against C. burnetii pulmonary infection. We also found that neither CXC chemokine receptor 2 (CXCR2) nor interleukin-17 (IL-17) receptor (IL-17R) deficiency changed the severity of disease following intranasal C. burnetii challenge, suggesting that keratinocyte-derived chemokine and IL-17 may not play essential roles in the response to C. burnetii infection. However, significantly higher C. burnetii genome copy numbers were detected in the lungs of IL-1R^−/− mice at 14 days postinfection. This indicates that IL-1 may be important for the clearance of C. burnetii from the lungs following intranasal infection. Our results also suggest that neutrophils are involved in protecting vaccinated mice from C. burnetii challenge-induced disease. This is the first study to demonstrate an important role for neutrophils in protective immunity against C. burnetii infection.     

Bone Microarchitecture Phenotypes Identified in Older Adults Are Associated With Different Levels of Osteoporotic Fracture Risk

Prevalence of osteoporosis is more than 50% in older adults, yet current clinical methods for diagnosis that rely on areal bone mineral density (aBMD) fail to detect most individuals who have a fragility fracture. Bone fragility can manifest in different forms, and a “one-size-fits-all” approach to diagnosis and management of osteoporosis may not be suitable. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides additive information by capturing information about volumetric density and microarchitecture, but interpretation is challenging because of the complex interactions between the numerous properties measured. In this study, we propose that there are common combinations of bone properties, referred to as phenotypes, that are predisposed to different levels of fracture risk. Using HR-pQCT data from a multinational cohort (n = 5873, 71% female) between 40 and 96 years of age, we employed fuzzy c-means clustering, an unsupervised machine-learning method, to identify phenotypes of bone microarchitecture. Three clusters were identified, and using partial correlation analysis of HR-pQCT parameters, we characterized the clusters as low density, low volume, and healthy bone phenotypes. Most males were associated with the healthy bone phenotype, whereas females were more often associated with the low volume or low density bone phenotypes. Each phenotype had a significantly different cumulative hazard of major osteoporotic fracture (MOF) and of any incident osteoporotic fracture (p < 0.05). After adjustment for covariates (cohort, sex, and age), the low density followed by the low volume phenotype had the highest association with MOF (hazard ratio = 2.96 and 2.35, respectively), and significant associations were maintained when additionally adjusted for femoral neck aBMD (hazard ratio = 1.69 and 1.90, respectively). Further, within each phenotype, different imaging biomarkers of fracture were identified. These findings suggest that osteoporotic fracture risk is associated with bone phenotypes that capture key features of bone deterioration that are not distinguishable by aBMD. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Recurrent Oral and Genital Ulcers in an Infant: Neonatal Presentation of Pediatric Behçet Disease

Behçet disease is a complex, multisystem disease characterized by recurrent oral and genital ulcerations. It rarely occurs in infants or children. Neonatal Behçet disease has been reported in infants whose ulcers resolve at or before 9 weeks of age. Few cases of neonatal Behçet disease persisting into childhood have previously been reported. We report the case of a 1‐month‐old infant who presented with severe recurrent genital ulcerations and at 6 months developed recurrent oral ulcerations. Her orogenital ulcerations continue to recur. Human leukocyte antigen testing revealed HLA‐B51 and B44 positivity. This is a case of pediatric Behçet disease in the neonatal period. Behçet disease should be considered in the differential diagnosis of recurrent genital and oral ulcerations in infants and children.     

Does Oil Rich in Alpha-Linolenic Fatty Acid Cause the Same Immune Modulation as Fish Oil in Walker 256 Tumor-Bearing Rats?

Objective: Polyunsaturated fatty acids n-3 (PUFA n-3) have shown effects in reducing tumor growth, in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) abundantly present in fish oil (FO). When these fatty acids are provided in the diet, they alter the functions of the cells, particularly in tumor and immune cells. However, the effects of α-linolenic fatty acid (ALA), which is the precursor of EPA and DHA, are controversial. Thus, our objective was to test the effect of this parental fatty acid. Methods: Non-tumor-bearing and tumor-bearing Wistar rats (70 days) were supplemented with 1 g/kg body weight of FO or Oro Inca® (OI) oil (rich in ALA). Immune cells function, proliferation, cytokine production, and subpopulation profile were evaluated. Results: We have shown that innate immune cells enhanced phagocytosis capacity, and increased processing and elimination of antigens. Moreover, there was a decrease in production of pro-inflammatory cytokines (tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6)) by macrophages. Lymphocytes showed decreased proliferation capacity, increased cluster of differentiation 8 (CD8⁺) subpopulation, and increased TNF-α production. Conclusions: Oil rich in ALA caused similar immune modulation in cancer when compared with FO.     

Binding mode of conformations and structure-based pharmacophore development for farnesyltransferase inhibitors

Farnesyltransferase (FTase) is one of the prenyltransferase family enzymes that catalyse the transfer of 15-membered isoprenoid (farnesyl) moiety to the cysteine of CAAX motif-containing proteins including Rho and Ras family of G proteins. Inhibitors of FTase act as drugs for cancer, malaria, progeria and other diseases. In the present investigation, we have developed two structure-based pharmacophore models from protein–ligand complex (3E33 and 3E37) obtained from the protein data bank. Molecular dynamics (MD) simulations were performed on the complexes, and different conformers of the same complex were generated. These conformers were undergone protein–ligand interaction fingerprint (PLIF) analysis, and the fingerprint bits have been used for structure-based pharmacophore model development. The PLIF results showed that Lys164, Tyr166, TrpB106 and TyrB361 are the major interacting residues in both the complexes. The RMSD and RMSF analyses on the MD-simulated systems showed that the absence of FPP in the complex 3E37 has significant effect in the conformational changes of the ligands. During this conformational change, some interactions between the protein and the ligands are lost, but regained after some simulations (after 2 ns). The structure-based pharmacophore models showed that the hydrophobic and acceptor contours are predominantly present in the models. The pharmacophore models were validated using reference compounds, which significantly identified as HITs with smaller RMSD values. The developed structure-based pharmacophore models are significant, and the methodology used in this study is novel from the existing methods (the original X-ray crystallographic coordination of the ligands is used for the model building). In our study, along with the original coordination of the ligand, different conformers of the same complex (protein–ligand) are used. It concluded that the developed methodology is significant for the virtual screening of novel molecules on different targets.