Neural circuit basis of placebo pain relief.

Placebo effects are notable demonstrations of mind-body interactions1,2. During pain perception, in the absence of any treatment, an expectation of pain relief can reduce the experience of pain-a phenomenon known as placebo analgesia3-6. However, despite the strength of placebo effects and their impact on everyday human experience and the failure of clinical trials for new therapeutics7, the neural circuit basis of placebo effects has remained unclear. Here we show that analgesia from the expectation of pain relief is mediated by rostral anterior cingulate cortex (rACC) neurons that project to the pontine nucleus (rACC→Pn)-a precerebellar nucleus with no established function in pain. We created a behavioural assay that generates placebo-like anticipatory pain relief in mice. In vivo calcium imaging of neural activity and electrophysiological recordings in brain slices showed that expectations of pain relief boost the activity of rACC→Pn neurons and potentiate neurotransmission in this pathway. Transcriptomic studies of Pn neurons revealed an abundance of opioid receptors, further suggesting a role in pain modulation. Inhibition of the rACC→Pn pathway disrupted placebo analgesia and decreased pain thresholds, whereas activation elicited analgesia in the absence of placebo conditioning. Finally, Purkinje cells exhibited activity patterns resembling those of rACC→Pn neurons during pain-relief expectation, providing cellular-level evidence for a role of the cerebellum in cognitive pain modulation. These findings open the possibility of targeting this prefrontal cortico-ponto-cerebellar pathway with drugs or neurostimulation to treat pain.

The presence of symptoms within 6 months after COVID-19: a single-center longitudinal study.

BACKGROUND: Characterizing the post-COVID health conditions is helpful to direct patients to appropriate healthcare. AIMS: To describe the presence of symptoms in COVID-19 patients within 6 months after diagnosis and to investigate the associated factors in terms of reporting symptoms. METHODS: Data of DEU-COVIMER (a telephone interview-based COVID-19 follow-up center established in a tertiary care hospital) was analyzed for SARS-CoV-2 RNA positive participants aged ≥ 18 years from November 1st, 2020, to May 31st, 2021. Symptom frequencies were stratified by demographic and clinical characteristics at one, three, and 6 months after diagnosis. With the patients who had symptoms at baseline, generalized estimating equations were applied to identify the factors associated with reporting of symptoms. RESULTS: A total of 5610 patients agreed to participate in the study. Symptom frequency was 37.2%, 21.8%, and 18.2% for the first, third, and sixth months. Tiredness/fatigue, muscle or body aches, and dyspnea/difficulty breathing were the most common symptoms in all time frames. In multivariate analysis, older age, female gender (odds ratio OR 1.74, 95% confidence interval 1.57-1.93), bad economic status (OR 1.37, 1.14-1.65), current smoking (OR 1.15, 1.02-1.29), being fully vaccinated before COVID-19 (OR 0.53, 0.40-0.72), having more health conditions (≥ 3 conditions, OR 1.78, 1.33-2.37), having more symptoms (> 5 symptoms, OR 2.47, 2.19-2.78), and hospitalization (intensive care unit, OR 2.18, 1.51-3.14) were associated with reporting of symptoms. CONCLUSIONS: This study identifies risk factors for patients who experience post-COVID-19 symptoms. Healthcare providers should appropriately allocate resources prioritizing the patients who would benefit from post-COVID rehabilitation.

Evaluation of possible COVID-19 reinfection in children: A multicenter clinical study.

BACKGROUND: Although it was originally unknown whether there would be cases of reinfection of coronavirus disease 2019 (COVID-19) as seen with other coronaviruses, cases of reinfection were reported from various regions recently. However, there is little information about reinfection in children. METHODS: In this study, we aimed to investigate the incidence and clinical findings of reinfection in pediatric patients who had recovered from COVID-19. We retrospectively evaluated all patients under 18 years of age with COVID-19 infection from a total of eight healthcare facilities in Turkey, between March 2020 and July 2021. Possible reinfection was defined as a record of confirmed COVID-19 infection based on positive reverse transcription-polymerase chain reaction (RT-PCR) test results at least 3 months apart. RESULTS: A possible reinfection was detected in 11 out of 8840 children, which yielded an incidence of 0.12%. The median duration between two episodes of COVID-19 was 196 (92-483) days. When initial and second episodes were compared, the rates of symptomatic and asymptomatic disease were similar for both, as was the severity of the disease (p = 1.000). Also, there was no significant difference in duration of symptoms (p = 0.498) or in hospitalization rates (p = 1.000). Only one patient died 15 days after PCR positivity, which resulted in a 9.1% mortality rate for cases of reinfection in pediatric patients. CONCLUSION: We observed that children with COVID-19 were less likely to be exposed to reinfection when compared with adults. Although the clinical spectrum of reinfection was mostly similar to the first episode, we reported death of a healthy child during the reinfection.

A General Analytical Approximation to Impulse Response of 3-D Microfluidic Channels in Molecular Communication.

In this paper, the impulse response for a 3-D microfluidic channel in the presence of Poiseuille flow is obtained by solving the diffusion equation in radial coordinates. Using the radial distribution, the axial distribution is then approximated accordingly. Since Poiseuille flow velocity changes with radial position, molecules have different axial properties for different radial distributions. We, therefore, present a piecewise function for the axial distribution of the molecules in the channel considering this radial distribution. We lay evidence for our theoretical derivations for impulse response of the microfluidic channel and radial distribution of molecules through comparing them using various Monte Carlo simulations. Finally, the communication performance of the channel is examined.

Comparison of blood culture and multiplex real-time PCR for the diagnosis of nosocomial sepsis.

BACKGROUND: In many cases of suspected sepsis, causative microorganisms cannot be isolated. Multiplex real-time PCR generates results more rapidly than conventional blood culture systems. METHODS: In this study, we evaluated the diagnostic performance of multiplex real-time PCR (LightCycler® SeptiFast, Roche, Mannheim, Germany), and compared with blood cultures and cultures from focus of infection in nosocomial sepsis. RESULTS: Seventy-eight nosocomial sepsis episodes in 67 adult patients were included in this study. The rates of microorganism detection by blood culture and PCR were 34.2% and 47.9%, respectively. Sixty-five microorganisms were detected by both methods from 78 sepsis episodes. Nineteen of these microorganisms were detected by both blood culture and PCR analysis from the same sepsis episode. There was statistically moderate concordance between the two methods (κ=0.445, P<0.001). There was no significant agreement between the blood culture and PCR analysis in terms of microorganism detected (κ=0.160, P=0.07). Comparison of the results of PCR and cultures from focus of infection revealed no significant agreement (κ=0.110, P=0.176). However, comparison of the results of PCR and blood cultures plus cultures from focus of infection (positive blood culture and/or positive culture from focus of infection) showed poor agreement (κ=0.17, P=0.026). When the blood culture was used as the gold standard, the sensitivity, specificity, positive and negative predictive value of PCR in patients with bacteremia was 80%, 69%, 57% and 87%, respectively. CONCLUSIONS: SeptiFast may be useful when added to blood culture in the diagnosis and management of sepsis.