Assessing the Intense Influenza A(H1N1)pdm09 Epidemic and Vaccine Effectiveness in the Post-COVID Season in the Russian Federation.

The COVID-19 pandemic had a profound impact on influenza activity worldwide. However, as the pandemic progressed, influenza activity resumed. Here, we describe the influenza epidemic of high intensity of the 2022-2023 season. The epidemic had an early start and peaked in week 51.2022. The extremely high intensity of the epidemic may have been due to a significant decrease in herd immunity. The results of PCR-testing of 220,067 clinical samples revealed that the influenza A(H1N1)pdm09 virus dominated, causing 56.4% of positive cases, while A(H3N2) influenza subtype accounted for only 0.6%, and influenza B of Victoria lineage-for 34.3%. The influenza vaccine was found to be highly effective, with an estimated effectiveness of 92.7% in preventing admission with laboratory-confirmed influenza severe acute respiratory illness (SARI) cases and 54.7% in preventing influenza-like illness/acute respiratory illness (ILI/ARI) cases due to antigenic matching of circulated viruses with influenza vaccine strains for the season. Full genome next-generation sequencing of 1723 influenza A(H1N1)pdm09 viruses showed that all of them fell within clade 6B.1A.5.a2; nine of them possessed H275Y substitution in the NA gene, a genetic marker of oseltamivir resistance. Influenza A(H3N2) viruses belonged to subclade 3C.2a1b.2a.2 with the genetic group 2b being dominant. All 433 influenza B viruses belonged to subclade V1A.3a.2 encoding HA1 substitutions A127T, P144L, and K203R, which could be further divided into two subgroups. None of the influenza A(H3N2) and B viruses sequenced had markers of resistance to NA inhibitors. Thus, despite the continuing circulation of Omicron descendant lineages, influenza activity has resumed in full force, raising concerns about the intensity of fore coming seasonal epidemics.

Inhibition of Cyclin-Dependent Kinases 8/19 Restricts Bacterial and Virus-Induced Inflammatory Responses in Monocytes.

Hyperactivation of the immune system remains a dramatic, life-threatening complication of viral and bacterial infections, particularly during pneumonia. Therapeutic approaches to counteract local and systemic outbreaks of cytokine storm and to prevent tissue damage remain limited. Cyclin-dependent kinases 8 and 19 (CDK8/19) potentiate transcriptional responses to the altered microenvironment, but CDK8/19 potential in immunoregulation is not fully understood. In the present study, we investigated how a selective CDK8/19 inhibitor, Senexin B, impacts the immunogenic profiles of monocytic cells stimulated using influenza virus H1N1 or bacterial lipopolysaccharides. Senexin B was able to prevent the induction of gene expression of proinflammatory cytokines in THP1 and U937 cell lines and in human peripheral blood-derived mononuclear cells. Moreover, Senexin B substantially reduced functional manifestations of inflammation, including clustering and chemokine-dependent migration of THP1 monocytes and human pulmonary fibroblasts (HPF).

Reduced Visual Evoked Potential Amplitude in Autistic Children with Co-Occurring Features of Attention-Deficit/Hyperactivity Disorder.

Provided the significant overlap in features of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), there is a critical need to identify transdiagnostic markers that could meaningfully stratify subgroups. The objective of this study was to compare the visual evoked potential (VEP) between 30 autistic children, 17 autistic children with co-occurring ADHD presentation (ASD + ADHD), and 21 neurotypical children (NTC). Electroencephalography was recorded while children passively viewed a pattern-reversal stimulus. Mean amplitude of the P1 event-related potential was extracted from a midline occipital channel and compared between groups. P1 mean amplitude was reduced in the ASD + ADHD group compared to the ASD and NTC groups, indicating a distinct pattern of brain activity in autistic children with co-occurring ADHD features.

Evaluation of clinical assessments of social abilities for use in autism clinical trials by the autism biomarkers consortium for clinical trials.

Clinical trials in autism spectrum disorder (ASD) often rely on clinician rating scales and parent surveys to measure autism-related features and social behaviors. To aid in the selection of these assessments for future clinical trials, the Autism Biomarkers Consortium for Clinical Trials (ABC-CT) directly compared eight common instruments with respect to acquisition rates, sensitivity to group differences, equivalence across demographic sub-groups, convergent validity, and stability over a 6-week period. The sample included 280 children diagnosed with ASD (65 girls) and 119 neurotypical children (36 girls) aged from 6 to 11 years. Full scale IQ for ASD ranged from 60 to 150 and for neurotypical ranged from 86 to 150. Instruments measured clinician global assessment and autism-related behaviors, social communication abilities, adaptive function, and social withdrawal behavior. For each instrument, we examined only the scales that measured social or communication functioning. Data acquisition rates were at least 97.5% at T1 and 95.7% at T2. All scales distinguished diagnostic groups. Some scales significantly differed by participant and/or family demographic characteristics. Within the ASD group, most clinical instruments exhibited weak (≥ |0.1|) to moderate (≥ |0.4|) intercorrelations. Short-term stability was moderate (ICC: 0.5-0.75) to excellent (ICC: >0.9) within the ASD group. Variations in the degree of stability may inform viability for different contexts of use, such as identifying clinical subgroups for trials versus serving as a modifiable clinical outcome. All instruments were evaluated in terms of their advantages and potential concerns for use in clinical trials.

Patterns of Intervention Utilization Among School-Aged Children with Autism Spectrum Disorder: Findings from a Multi-Site Research Consortium.

When designing and interpreting results from clinical trials evaluating treatments for children on the autism spectrum, a complicating factor is that most children receive a range of concurrent treatments. Thus, it is important to better understand the types and hours of interventions that participants typically receive as part of standard of care, as well as to understand the child, family, and geographic factors that are associated with different patterns of service utilization. In this multi-site study, we interviewed 280 caregivers of 6-to-11-year-old school-aged children on the autism spectrum about the types and amounts of interventions their children received in the prior 6 weeks. Reported interventions were coded as "evidence-based practice" or "other interventions," reflecting the level of empirical support. Results indicated that children received a variety of interventions with varying levels of empirical evidence and a wide range of hours (0 to 79.3 hours/week). Children with higher autism symptom levels, living in particular states, and who identified as non-Hispanic received more evidence-based intervention hours. Higher parental education level related to more hours of other interventions. Children who were younger, had lower cognitive ability, and with higher autism symptom levels received a greater variety of interventions overall. Thus, based on our findings, it would seem prudent when designing clinical trials to take into consideration a variety of factors including autism symptom levels, age, cognitive ability, ethnicity, parent education and geographic location. Future research should continue to investigate the ethnic, racial, and socioeconomic influences on school-aged intervention services.

Social EEG: A novel neurodevelopmental approach to studying brain-behavior links and brain-to-brain synchrony during naturalistic toddler-parent interactions.

Despite increasing emphasis on emergent brain-behavior patterns supporting language, cognitive, and socioemotional development in toddlerhood, methodologic challenges impede their characterization. Toddlers are notoriously difficult to engage in brain research, leaving a developmental window in which neural processes are understudied. Further, electroencephalography (EEG) and event-related potential paradigms at this age typically employ structured, experimental tasks that rarely reflect formative naturalistic interactions with caregivers. Here, we introduce and provide proof of concept for a new "Social EEG" paradigm, in which parent-toddler dyads interact naturally during EEG recording. Parents and toddlers sit at a table together and engage in different activities, such as book sharing or watching a movie. EEG is time locked to the video recording of their interaction. Offline, behavioral data are microcoded with mutually exclusive engagement state codes. From 216 sessions to date with 2- and 3-year-old toddlers and their parents, 72% of dyads successfully completed the full Social EEG paradigm, suggesting that it is possible to collect dual EEG from parents and toddlers during naturalistic interactions. In addition to providing naturalistic information about child neural development within the caregiving context, this paradigm holds promise for examination of emerging constructs such as brain-to-brain synchrony in parents and children.

Functional Organization of the Temporal-Parietal Junction for Theory of Mind in Preverbal Infants: A Near-Infrared Spectroscopy Study.

Successful human social life requires imagining what others believe or think to understand and predict behavior. This ability, often referred to as theory of mind (ToM), reliably engages a specialized network of temporal and prefrontal brain regions in older children and adults, including selective recruitment of the temporal-parietal junction (TPJ). To date, how and when this specialized brain organization for ToM arises is unknown due to limitations in functional neuroimaging at younger ages. Here, we used the emerging technique of functional near-infrared spectroscopy to measure the functional brain response across parietal, temporal, and prefrontal regions in 7-month-old male and female infants as they viewed different video scenarios of a person searching for a hidden object. Over different conditions, we manipulated whether the person held an accurate (true) or inaccurate (false) belief about the location of the hidden object in the videos. In two separate experiments, we observed that activity from the TPJ, but not other temporal and prefrontal regions, spontaneously tracked with the beliefs of the other person, responding more during scenarios when the other person's belief regarding the location of the object was false compared with scenarios when her belief was true. These results mirror those obtained with adults to show that the TPJ already shows some functional organization relevant to high-level social cognition by around 7 months of age. Furthermore, these results suggest that infants may draw on similar core mechanisms to implicitly track beliefs, as adults do when reasoning explicitly about them.SIGNIFICANCE STATEMENT Humans selectively engage a network of brain regions, including the temporal-parietal junction (TPJ), to track what others think, an ability referred to as theory of mind. How and when this specialized brain organization for high-level social cognition arises is unknown. Using the emerging technique of near-infrared spectroscopy with 7-month-old infants, we observed that activity of the TPJ, but not other temporal and frontal regions, distinguished between scenarios when another person's belief about the location of the object was false compared with scenarios when the belief was true. These results suggest that a basic neural architecture to understand and predict the actions of others based on their beliefs may be present from the first year of life.