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One of the primary means of communicating with a baby is through touch. Nurturing physical touch promotes healthy physiological development in social mammals, including humans. Physiology influences wellbeing and psychosocial functioning. The purpose of this paper is to explore the connections among early life positive and negative touch and wellbeing and sociomoral development. In study 1, mothers of preschoolers ( n = 156) reported their attitudes toward positive/negative touch and on their children’s wellbeing and sociomoral outcomes, illustrating moderate to strong positive correlations between positive touch attitudes and children’s sociomoral capacities and orientations and negative correlations with psychopathology. In study 2, we used an existing longitudinal dataset, with at-risk mothers ( n = 682) and their children to test touch effects on moral capacities and social behaviors in early life. Results demonstrated moderate to strong relationships between positive/negative touch and concurrent child behavioral regulation and positive correlations between low corporal punishment and child sociomoral outcomes. In a third study with adults ( n = 607), we found significant mediation processes connecting retrospective reports of childhood touch to adult moral orientation through attachment security, mental health, and moral capacities. In general across studies, more affectionate touch and less punishing touch were positively associated with wellbeing and development of moral capacities and engaged moral orientation.

Evolutionary systems theory identifies niches as key developmental inheritances for animals. The human evolved developmental niche (EDN) is characterized by positive touch, responsiveness, play, and social togetherness and provides the responsive, relational dynamism that optimizes development. Cross-sectional and longitudinal studies of the human EDN have demonstrated correlations between degree of EDN consistency in early childhood and positive sociomoral development and avoidance of ill-being and misbehavior. We created a brief report of children’s recent EDN experience and examined its relation to child well-being and sociomoral development. Using samples from three cultures (United States, N=574; Switzerland, N=96; China, N=382), EDN provision in the past week was related to multiple child outcomes even after controlling for parental age, education, income, responsivity, and child gender. Factor analyses indicated three sets of latent factors in each sample: Moral Socialization, Social Maladaptation, and Social Thriving. Structural equation models indicated that EDN provision significantly predicted Social Thriving in all samples beyond control variables. EDN provision may be particularly helpful in predicting optimal social development.

The parent-child relationship, foundational to a child’s self-regulation, functions best when parents are sensitive and provide affection. Through these important relational aspects, infants and young children become able to regulate arousal. The current study examined both emotion and behavior regulation within the context of the parent-child relationship. Emotion regulation was examined on a micro-level during infancy and behavior regulation was measured when children were four-years old. It was hypothesized, but not supported, that infants who received more touch during the baseline segment would recover faster during the reunion segment of the still-face paradigm. Results showed that micro-level emotion regulation during the reunion segment was predictive of behavior regulation at age four. The current study shows how the still-face paradigm can be useful in capturing a micro-level snapshot of the child’s developing regulatory functions and the relation to behavior regulation years later.

A widely used technique for coordinate-based meta-analysis of neuroimaging data is activation likelihood estimation (ALE), which determines the convergence of foci reported from different experiments. ALE analysis involves modelling these foci as probability distributions whose width is based on empirical estimates of the spatial uncertainty due to the between-subject and between-template variability of neuroimaging data. ALE results are assessed against a null-distribution of random spatial association between experiments, resulting in random-effects inference. In the present revision of this algorithm, we address two remaining drawbacks of the previous algorithm. First, the assessment of spatial association between experiments was based on a highly time-consuming permutation test, which nevertheless entailed the danger of underestimating the right tail of the null-distribution. In this report, we outline how this previous approach may be replaced by a faster and more precise analytical method. Second, the previously applied correction procedure, i.e. controlling the false discovery rate (FDR), is supplemented by new approaches for correcting the family-wise error rate and the cluster-level significance. The different alternatives for drawing inference on meta-analytic results are evaluated on an exemplary dataset on face perception as well as discussed with respect to their methodological limitations and advantages. In summary, we thus replaced the previous permutation algorithm with a faster and more rigorous analytical solution for the null-distribution and comprehensively address the issue of multiple-comparison corrections. The proposed revision of the ALE-algorithm should provide an improved tool for conducting coordinate-based meta-analyses on functional imaging data. ► The permutation procedure of ALE is replaced by a faster and more accurate approach. ► Family-wise error correction and cluster-level inference are introduced into ALE. ► The current and revised implementation of ALE yields comparable results.

Whether we feel sympathy for another, listen to our heartbeat, experience pain or negotiate, the insular cortex is thought to integrate perceptions, emotions, thoughts, and plans into one subjective image of “our world”. The insula has hence been ascribed an integrative role, linking information from diverse functional systems. Nevertheless, various anatomical and functional studies in humans and non-human primates also indicate a functional differentiation of this region. In order to investigate this functional differentiation as well as the mechanisms of the functional integration in the insula, we performed activation-likelihood-estimation (ALE) meta-analyses of 1,768 functional neuroimaging experiments. The analysis revealed four functionally distinct regions on the human insula, which map to the social-emotional, the sensorimotor, the olfacto-gustatory, and the cognitive network of the brain. Sensorimotor tasks activated the mid-posterior and social-emotional tasks the anterior-ventral insula. In the central insula activation by olfacto-gustatory stimuli was found, and cognitive tasks elicited activation in the anterior-dorsal region. A conjunction analysis across these domains revealed that aside from basic somatosensory and motor processes all tested functions overlapped on the anterior-dorsal insula. This overlap might constitute a correlate for a functional integration between different functional systems and thus reflect a link between them necessary to integrate different qualities into a coherent experience of the world and setting the context for thoughts and actions.

Massive apoptosis of lymphocytes is a hallmark of sepsis. The resulting immunosuppression is associated with secondary infections, which are often lethal. Moreover, sepsis-survivors are burdened with increased morbidity and mortality for several years after the sepsis episode. The duration and clinical consequences of sepsis induced-immunosuppression are currently unknown. We have used the mouse model of peritoneal contamination and infection (PCI) to investigate the quantitative and qualitative recovery of T lymphocytes for 3.5 months after sepsis with or without IL-7 treatment. Thymic output and the numbers of naive and effector/memory CD4+ and CD8+ lymphocytes quickly recovered after sepsis. IL-7 treatment resulted in an accelerated recovery of CD8+ lymphocytes. Next generation sequencing revealed no significant narrowing of the T cell receptor repertoire 3.5 months after sepsis. In contrast, detailed functional analyses of T helper (Th)-cell responses towards a fungal antigen revealed a significant loss of Th cells. Whereas cytokine production was not impaired at the single cell level, the absolute number of Th cells specific for the fungal antigen was reduced. Our data indicate a clinically relevant loss of pathogen-specific T cell clones after sepsis. Given the small number of naive T lymphocytes specific for a given antigen, this decrement of T cell clones remains undetected even by sensitive methods such as deep sequencing. Taken together, our data are compatible with long lasting impairments in CD4+ T-cell responses after sepsis despite rapid recovery of T lymphocyte populations.

A shortage of artemether–lumefantrine at the Ebola treatment center in Liberia led to the use of artesunate–amodiaquine for malaria treatment during a 12-day period. In this setting, artesunate–amodiaquine use was associated with a 31% lower risk of death from Ebola. The outbreak of Ebola virus disease (EVD) in West Africa has led to more than 28,000 cases and has claimed more than 11,000 lives since the outbreak was first declared in March 2014, with most of the burden of disease observed in Guinea, Sierra Leone, and Liberia. 1 Few treatment practices or therapeutics are known to significantly reduce the risk of death. Recent in vitro assessments of drugs that have been approved by the U.S. Food and Drug Administration for anti-EVD activity have identified a number of candidates among compounds that are used to treat other diseases, including malaria. 2 However, little . . .

Background Epilepsy and other seizure disorders account for a high disease burden in Germany. As a timely diagnosis and accurate treatment are crucial, improving the management of these disorders is important. Outside of Germany, outpatient long-term video EEGs (ALVEEGs) have demonstrated the potential to support the diagnosis and management of epilepsy and other seizure disorders. This study aims to evaluate the implementation of ALVEEGs as a new diagnostic pathway in eastern parts of Germany to diagnose epilepsy and other seizure disorders and to assess if ALVEEGs are equally effective as the current inpatient-monitoring gold standard, which is currently only available at a limited number of specialized centers in Germany. Methods ALVEEG is a prospective, multicenter, randomized controlled equivalence trial, involving five epilepsy centers in the eastern states of Germany. Patients will be randomized into either intervention (IG) or control group (CG), using a permuted block randomization. The sample size targeted is 688 patients, continuously recruited over the trial. The IG will complete an ALVEEG in a home setting, including getting access to a smartphone app to document seizure activity. The CG will receive care as usual, i.e., inpatient long-term video-EEG monitoring. The primary outcome is the proportion of clinical questions being solved in the IG compared to the CG. Secondary outcomes include hospital stays, time until video EEG, time until diagnosis and result discussion, patients’ health status, quality of life and health competence, and number and form of epilepsy-related events and epileptiform activity. Alongside the trial, a process implementation and health economic evaluation will be conducted. Discussion The extensive evaluation of this study, including an implementation and health economic evaluation, will provide valuable information for health policy decision-makers to optimize future delivery of neurological care to patients affected by epilepsy and other seizure disorders and on the uptake of ALVEEG into standard care in Germany. Trial registration German Clinical Trials Register (DRKS00032220), date registered: December 11, 2023.

Voltage-gated sodium channel Nav1.9 is a threshold channel that regulates action potential firing. Nav1.9 is preferentially expressed in myenteric neurons, and small-diameter dorsal root ganglion (DRG) and trigeminal ganglion neurons including nociceptors. Recent studies have demonstrated a monogenic Mendelian link of Nav1.9 to human pain disorders. Gain-of-function variants in Nav1.9, which cause smaller depolarizations of RMP, have been identified in patients with familial episodic pain type 3 (FEPS3) and the more common pain disorder small fiber neuropathy. To explore the phenotypic spectrum of Nav1.9 channelopathy, here we report a new Nav1.9 mutation, N816K, in a child with early-onset episodic pain in both legs, episodic abdominal pain, and chronic constipation. Sequencing of further selected pain genes was normal. N816K alters a residue at the N-terminus of loop 2, proximal to the cytoplasmic terminus of transmembrane segment 6 in domain II. Voltage-clamp recordings demonstrate that Nav1.9-N816K significantly increases current density and hyperpolarizes voltage-dependence of activation by 10 mV, enabling a larger window current. Current-clamp recordings in DRG neurons shows that N816K channels depolarize RMP of small DRG neurons by 7 mV, reduce current threshold of firing an action potential and render DRG neurons hyperexcitable. Taken together these data demonstrate gain-of-function attributes of the newly described N816K mutation at the channel and cellular levels, which are consistent with a pain phenotype in the carrier of this mutation.

Analysis of 179 new Ebola virus sequences from patient samples collected in Guinea between March 2014 and January 2015 shows how different lineages evolved and spread in West Africa. Ebola virus lineage evolution Miles Carroll and colleagues report describe the genetic evolution of Ebola virus circulating in West Africa, based on 179 new virus sequences from patient samples collected in Guinea between March 2014 and January 2015. Their analysis shows how different lineages evolved and spread in West Africa between Sierra Leone, Guinea and Liberia. West Africa is currently witnessing the most extensive Ebola virus (EBOV) outbreak so far recorded 1 , 2 , 3 . Until now, there have been 27,013 reported cases and 11,134 deaths. The origin of the virus is thought to have been a zoonotic transmission from a bat to a two-year-old boy in December 2013 (ref. 2 ). From this index case the virus was spread by human-to-human contact throughout Guinea, Sierra Leone and Liberia. However, the origin of the particular virus in each country and time of transmission is not known and currently relies on epidemiological analysis, which may be unreliable owing to the difficulties of obtaining patient information. Here we trace the genetic evolution of EBOV in the current outbreak that has resulted in multiple lineages. Deep sequencing of 179 patient samples processed by the European Mobile Laboratory, the first diagnostics unit to be deployed to the epicentre of the outbreak in Guinea, reveals an epidemiological and evolutionary history of the epidemic from March 2014 to January 2015. Analysis of EBOV genome evolution has also benefited from a similar sequencing effort of patient samples from Sierra Leone. Our results confirm that the EBOV from Guinea moved into Sierra Leone, most likely in April or early May. The viruses of the Guinea/Sierra Leone lineage mixed around June/July 2014. Viral sequences covering August, September and October 2014 indicate that this lineage evolved independently within Guinea. These data can be used in conjunction with epidemiological information to test retrospectively the effectiveness of control measures, and provides an unprecedented window into the evolution of an ongoing viral haemorrhagic fever outbreak.