A network analysis of the Fear of COVID-19 Scale (FCV-19S): a large-scale cross-cultural study in Iran, Bangladesh, and Norway

The rapid spread of the coronavirus disease 2019 (COVID-19) has led to high levels of fear worldwide. Given that fear is an important factor in causing psychological distress and facilitating preventive behaviors, assessing the fear of COVID-19 is important. The seven-item Fear of COVID-19 Scale (FCV-19S) is a widely used psychometric instrument to assess this fear. However, the factor structure of the FCV-19S remains unclear according to the current evidence. Therefore, the present study used a network analysis to provide further empirical evidence for the factor structure of FCV-19S. A total of 24,429 participants from Iran (n = 10,843), Bangladesh (n = 9906), and Norway (n = 3680) completed the FCV-19S in their local language. A network analysis (via regularized partial correlation networks) was applied to investigate the seven FCV-19S items. Moreover, relationships between the FCV-19S items were compared across gender (males vs. females), age groups (18-30 years, 31-50 years, and >50 years), and countries (Iran, Bangladesh, and Norway). A two-factor structure pattern was observed (three items concerning physical factors, including clammy hands, insomnia, and heart palpitations; four items concerning psychosocial factors, including being afraid, uncomfortable, afraid of dying, and anxious about COVID-19 news). Moreover, this pattern was found to be the same among men and women, across age groups and countries. The network analysis used in the present study verified the two-factor structure for the FCV-19S. Future studies may consider using the two-factor structure of FCV-19S to assess the fear of COVID-19 during the COVID-19 era

Sequential Broadening of CTL Responses in Early HIV-1 Infection Is Associated with Viral Escape

BACKGROUND: Antigen-specific CTL responses are thought to play a central role in containment of HIV-1 infection, but no consistent correlation has been found between the magnitude and/or breadth of response and viral load changes during disease progression. METHODS AND FINDINGS: We undertook a detailed investigation of longitudinal CTL responses and HIV-1 evolution beginning with primary infection in 11 untreated HLA-A2 positive individuals. A subset of patients developed broad responses, which selected for consensus B epitope variants in Gag, Pol, and Nef, suggesting CTL-induced adaptation of HIV-1 at the population level. The patients who developed viral escape mutations and broad autologous CTL responses over time had a significantly higher increase in viral load during the first year of infection compared to those who did not develop viral escape mutations. CONCLUSIONS: A continuous dynamic development of CTL responses was associated with viral escape from temporarily effective immune responses. Our results suggest that broad CTL responses often represent footprints left by viral CTL escape rather than effective immune control, and help explain earlier findings that fail to show an association between breadth of CTL responses and viral load. Our results also demonstrate that CTL pressures help to maintain certain elements of consensus viral sequence, which likely represent viral escape from common HLA-restricted CTL responses. The ability of HIV to evolve to escape CTL responses restricted by a common HLA type highlights the challenges posed to development of an effective CTL-based vaccine

Optimizing Taq Polymerase Concentration for Improved Signal-to-Noise in the Broad Range Detection of Low Abundance Bacteria

BACKGROUND:PCR in principle can detect a single target molecule in a reaction mixture. Contaminating bacterial DNA in reagents creates a practical limit on the use of PCR to detect dilute bacterial DNA in environmental or public health samples. The most pernicious source of contamination is microbial DNA in DNA polymerase preparations. Importantly, all commercial Taq polymerase preparations inevitably contain contaminating microbial DNA. Removal of DNA from an enzyme preparation is problematical. METHODOLOGY/PRINCIPAL FINDINGS:This report demonstrates that the background of contaminating DNA detected by quantitative PCR with broad host range primers can be decreased greater than 10-fold through the simple expedient of Taq enzyme dilution, without altering detection of target microbes in samples. The general method is: For any thermostable polymerase used for high-sensitivity detection, do a dilution series of the polymerase crossed with a dilution series of DNA or bacteria that work well with the test primers. For further work use the concentration of polymerase that gave the least signal in its negative control (H(2)O) while also not changing the threshold cycle for dilutions of spiked DNA or bacteria compared to higher concentrations of Taq polymerase. CONCLUSIONS/SIGNIFICANCE:It is clear from the studies shown in this report that a straightforward procedure of optimizing the Taq polymerase concentration achieved "treatment-free" attenuation of interference by contaminating bacterial DNA in Taq polymerase preparations. This procedure should facilitate detection and quantification with broad host range primers of a small number of bona fide bacteria (as few as one) in a sample

Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer: post hoc analysis of PREVAIL.

Background Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA monitoring alone to determine disease status on therapy. This approach has not been adequately tested.Methods Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide in the PREVAIL study were analyzed post hoc for rising versus nonrising PSA (empirically defined as >1.05 vs ⩽1.05 times the PSA level from 3 months earlier) at the time of radiographic progression. Clinical characteristics and disease outcomes were compared between the rising and nonrising PSA groups.Results Of 265 PREVAIL patients with radiographic progression and evaluable PSA levels on the enzalutamide arm, nearly one-quarter had a nonrising PSA. Median progression-free survival in this cohort was 8.3 months versus 11.1 months in the rising PSA cohort (hazard ratio 1.68; 95% confidence interval 1.26-2.23); overall survival was similar between the two groups, although less than half of patients in either group were still at risk at 24 months. Baseline clinical characteristics of the two groups were similar.Conclusions Non-rising PSA at radiographic progression is a common phenomenon in mCRPC patients treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant on serial serum PSA measurement may more accurately identify disease progression

Involvement of calcitonin gene-related peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients

Calcitonin gene-related peptide (CGRP)-containing nerves are closely associated with cranial blood vessels. CGRP is the most potent vasodilator known in isolated cerebral blood vessels. CGRP can induce migraine attacks, and two selective CGRP receptor antagonists are effective in the treatment of migraine attacks. It is therefore important to investigate its mechanism of action in patients with migraine. We here investigate the effects of intravenous human alpha-CGRP (hαCGRP) on intracranial hemodynamics. In a double-blind, cross-over study, the effect of intravenous infusion of hαCGRP (2 μg/min) or placebo for 20 min was studied in 12 patients with migraine without aura outside attacks. Xenon-133 inhalation SPECT-determined regional cerebral blood flow (rCBF) and transcranial Doppler (TCD)-determined blood velocity (Vmean) in the middle cerebral artery (MCA), as well as the heart rate and blood pressure, were the outcome parameters. No change of rCBF was observed at the end of infusion [1.2% ± 1.7 with hαCGRP, vs. −1.6% ± 3.1 with placebo (mean ± SD)] (P = 0.43). Vmean in MCA decreased to 13.5% ± 3.6 with hαCGRP versus 0.6% ± 1.8 with placebo (P < 0.005). Since rCBF was unchanged, this indicates a dilation of the MCA. hαCGRP induced a decrease in MAP (12%) (P < 0.005) and an increase in heart rate (58%) (P < 0.0001). CGRP dilates cerebral arteries, but the effect is so small that it is unlikely to be the only mechanism of CGRP-induced migraine

Evaluation of the national surveillance system for point-prevalence of healthcare-associated infections in hospitals and in long-term care facilities for elderly in Norway, 2002-2008

<p>Abstract</p> <p>Background</p> <p>Since 2002, the Norwegian Institute of Public Health has invited all hospitals and long-term care facilities for elderly (LTCFs) to participate in two annual point-prevalence surveys covering the most frequent types of healthcare-associated infections (HAIs). In a comprehensive evaluation we assessed how well the system operates to meet its objectives.</p> <p>Methods</p> <p>Surveillance protocols and the national database were reviewed. Data managers at national level, infection control practitioners and ward personnel in hospitals as well as contact persons in LTCFs involved in prevalence data collection were surveyed.</p> <p>Results</p> <p>The evaluation showed that the system was structurally simple, flexible and accepted by the key partners. On average 87% of hospitals and 32% of LTCFs participated in 2004-2008; high level of data completeness was achieved. The data collected described trends in the prevalence of reportable HAIs in Norway and informed policy makers. Local results were used in hospitals to implement targeted infection control measures and to argue for more resources to a greater extent than in LTCFs. Both the use of simplified Centers for Disease Control and Prevention (CDC) definitions and validity of data seemed problematic as compliance with the standard methodology were reportedly low.</p> <p>Conclusions</p> <p>The surveillance system provides important information on selected HAIs in Norway. The system is overall functional and well-established in hospitals, however, requires active promotion in LTCFs. Validity of data needs to be controlled in the participating institutions before reporting to the national level.</p

Natural CD4+ T-Cell Responses against Indoleamine 2,3-Dioxygenase

The enzyme indoleamine 2,3-dioxygenase (IDO) contributes to immune tolerance in a variety of settings. In cancer IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it endorses the establishment of peripheral immune tolerance to tumor antigens. Recently, we described cytotoxic CD8(+) T-cell reactivity towards IDO-derived peptides.In the present study, we show that CD4(+) helper T cells additionally spontaneously recognize IDO. Hence, we scrutinized the vicinity of the previously described HLA-A*0201-restricted IDO-epitope for CD4(+) T-cell epitopes. We demonstrated the presence of naturally occurring IDO-specific CD4(+) T cells in cancer patients and to a lesser extent in healthy donors by cytokine release ELISPOT. IDO-reactive CD4(+) T cells released IFN-γ, TNF-α, as well as IL-17. We confirm HLA class II-restriction by the addition of HLA class II specific blocking antibodies. In addition, we detected a trend between class I- and class II-restricted IDO responses and detected an association between IDO-specific CD4(+) T cells and CD8(+) CMV-responses. Finally, we could detect IL-10 releasing IDO-reactive CD4(+) T cells.IDO is spontaneously recognized by HLA class II-restricted, CD4(+) T cells in cancer patients and in healthy individuals. IDO-specific T cells may participate in immune-regulatory networks where the activation of pro-inflammatory IDO-specific CD4(+) responses may well overcome or delay the immune suppressive actions of the IDO-protein, which are otherwise a consequence of the early expression of IDO in maturing antigen presenting cells. In contrast, IDO-specific regulatory T cells may enhance IDO-mediated immune suppression

Psychiatric diagnoses and punishment for misconduct: the effects of PTSD in combat-deployed Marines

<p>Abstract</p> <p>Background</p> <p>Research on Vietnam veterans suggests an association between psychological problems, including posttraumatic stress disorder (PTSD), and misconduct; however, this has rarely been studied in veterans of Operation Iraqi Freedom or Operation Enduring Freedom. The objective of this study was to investigate whether psychological problems were associated with three types of misconduct outcomes (demotions, drug-related discharges, and punitive discharges.)</p> <p>Methods</p> <p>A population-based study was conducted on all U.S. Marines who entered the military between October 1, 2001, and September 30, 2006, and deployed outside of the United States before the end of the study period, September 30, 2007. Demographic, psychiatric, deployment, and personnel information was collected from military records. Cox proportional hazards regression analysis was conducted to investigate associations between the independent variables and the three types of misconduct in war-deployed (n = 77 998) and non-war-deployed (n = 13 944) Marines.</p> <p>Results</p> <p>Marines in both the war-deployed and non-war-deployed cohorts with a non-PTSD psychiatric diagnosis had an elevated risk for all three misconduct outcomes (hazard ratios ranged from 3.93 to 5.65). PTSD was a significant predictor of drug-related discharges in both the war-deployed and non-war-deployed cohorts. In the war-deployed cohort only, a specific diagnosis of PTSD was associated with an increased risk for both demotions (hazard ratio, 8.60; 95% confidence interval, 6.95 to 10.64) and punitive discharges (HR, 11.06; 95% CI, 8.06 to 15.16).</p> <p>Conclusions</p> <p>These results provide evidence of an association between PTSD and behavior problems in Marines deployed to war. Moreover, because misconduct can lead to disqualification for some Veterans Administration benefits, personnel with the most serious manifestations of PTSD may face additional barriers to care.</p

Increased cholinergic contractions of jejunal smooth muscle caused by a high cholesterol diet are prevented by the 5-HT(4 )agonist – tegaserod

BACKGROUND: Excess cholesterol in bile and in blood is a major risk factor for the respective development of gallbladder disease and atherosclerosis. This lipid in excess negatively impacts the functioning of other smooth muscles, including the intestine. Serotonin is an important mediator of the contractile responses of the small intestine. Drugs targeting the serotonin receptor are used as prokinetic agents to manage intestinal motor disorders, in particular irritable bowel syndrome. Thus, tegaserod, acting on 5-HT(4 )receptor, ideally should obviate detrimental effects of excessive cholesterol on gastrointestinal smooth muscle. In this study we examined the effect of tegaserod on cholesterol-induced changes in the contractile responses of intestinal smooth muscle. METHODS: The effects of a high cholesterol (1%) diet on the in vitro contractile responses of jejunal longitudinal smooth muscle from Richardson ground squirrels to the cholinergic agonist carbachol were examined in the presence or absence of tetrodrodotoxin (TTX). Two groups of animals, fed either low (0.03%) or high cholesterol rat chow diet, were further divided into two subgroups and treated for 28 days with either vehicle or tegaserod. RESULTS: The high cholesterol diet increased, by nearly 2-fold, contractions of the jejunal longitudinal smooth muscle elicited by carbachol. These cholinergic contractions were mediated by muscarinic receptors since they were blocked by scopolamine, a muscarinic receptor antagonist, but not by the nicotinic receptor antagonist, hexamethonium. Tegaserod treatment, which did not affect cholinergic contractions of tissues from low cholesterol fed animals, abrogated the increase caused by the high cholesterol diet. With low cholesterol diet TTX enhanced carbachol-evoked contractions, whereas this action potential blocker did not affect the augmented cholinergic contractions seen with tissues from animals on the high cholesterol diet. Tegaserod-treatment removed the effects of a high cholesterol diet on neuronal muscarinic receptors, as the potentiating effect of TTX on carbachol-elicited contractions was maintained in these animals. CONCLUSION: A high cholesterol diet causes significant changes to cholinergic neurotransmission in the enteric nerves of the jejunum. The mechanisms by which these effects of cholesterol are reversed by tegaserod are unknown, but relate to removal of an inhibitory effect of cholesterol on enteric nerves