ObjectiveOur objective was to review the characteristics, current applications, and evaluation measures of conversational agents with unconstrained natural language input capabilities used for health-related purposes.MethodsWe searched PubMed, Embase, CINAHL, PsycInfo, and ACM Digital using a predefined search strategy. Studies were included if they focused on consumers or healthcare professionals; involved a conversational agent using any unconstrained natural language input; and reported evaluation measures resulting from user interaction with the system. Studies were screened by independent reviewers and Cohen’s kappa measured inter-coder agreement.ResultsThe database search retrieved 1513 citations; 17 articles (14 different conversational agents) met the inclusion criteria. Dialogue management strategies were mostly finite-state and frame-based (6 and 7 conversational agents, respectively); agent-based strategies were present in one type of system. Two studies were randomized controlled trials (RCTs), 1 was cross-sectional, and the remaining were quasi-experimental. Half of the conversational agents supported consumers with health tasks such as self-care. The only RCT evaluating the efficacy of a conversational agent found a significant effect in reducing depression symptoms (effect size d = 0.44, p = .04). Patient safety was rarely evaluated in the included studies.ConclusionsThe use of conversational agents with unconstrained natural language input capabilities for health-related purposes is an emerging field of research, where the few published studies were mainly quasi-experimental, and rarely evaluated efficacy or safety. Future studies would benefit from more robust experimental designs and standardized reporting.Protocol RegistrationThe protocol for this systematic review is registered at PROSPERO with the number CRD42017065917.

Many primary sensory neurons are polymodal, responding to multiple stimulus modalities (chemical, thermal, or mechanical), yet each modality is recognized differently. While polymodality implies that stimulus encoding occurs in higher centers such as the spinal cord or brain, recent sensory neuron ablation studies find that behavioral responses to different modalities require distinct subpopulations, suggesting the existence of modality-specific labeled-lines at the level of the sensory afferent. Here we provide evidence that neurons expressing TRPM8, a cold- and menthol-gated channel required for normal cold responses in mammals, represents a labeled-line solely for cold sensation. We examined the behavioral significance of conditionally ablating TRPM8+ neurons in adult mice, finding that, like animals lacking TRPM8 channels (Trpm8−/−), animals depleted of TRPM8 neurons (ablated) are insensitive to cool to painfully cold temperatures. Ablated animals showed little aversion to noxious cold and did not distinguish between cold and a preferred warm temperature, a phenotype more profound than that of Trpm8−/− mice which exhibit only partial cold avoidance and preference behaviors. In addition to acute responses, cold pain associated with inflammation and nerve injury was significantly attenuated in ablated and Trpm8−/− mice. Moreover, cooling-induced analgesia after nerve injury was abolished in both genotypes. Lastly, heat, mechanical, and proprioceptive behaviors were normal in ablated mice, demonstrating that TRPM8 neurons are dispensable for other somatosensory modalities. Together these data show that while some limited cold sensitivity remains in Trpm8−/− mice, TRPM8 neurons are required for the breadth of behavioral responses evoked by cold temperatures.

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Sex differences in age- and puberty-related maturation of human brain structure have been observed in typically developing age-matched boys and girls. Because girls mature 1-2 years earlier than boys, the present study aimed at assessing sex differences in brain structure by studying 80 adolescent boys and girls matched on sexual maturity, rather than age. We evaluated pubertal influences on medial temporal lobe (MTL), thalamic, caudate, and cortical gray matter volumes utilizing structural magnetic resonance imaging and 2 measures of pubertal status: physical sexual maturity and circulating testosterone. As predicted, significant interactions between sex and the effect of puberty were observed in regions with high sex steroid hormone receptor densities; sex differences in the right hippocampus, bilateral amygdala, and cortical gray matter were greater in more sexually mature adolescents. Within sex, we found larger volumes in MTL structures in more sexually mature boys, whereas smaller volumes were observed in more sexually mature girls. Our results demonstrate puberty-related maturation of the hippocampus, amygdala, and cortical gray matter that is not confounded by age, and is different for girls and boys, which may contribute to differences in social and cognitive development during adolescence, and lasting sexual dimorphisms in the adult brain.

We sequenced the genomes of 10 Salmonella enterica serovar Infantis isolates containing bla CTX-M-65 obtained from chicken, cattle, and human sources collected between 2012 and 2015 in the United States through routine National Antimicrobial Resistance Monitoring System (NARMS) surveillance and product sampling programs. We also completely assembled the plasmids from four of the isolates. All isolates had a D87Y mutation in the gyrA gene and harbored between 7 and 10 resistance genes [aph(4)-Ia, aac(3)-IVa, aph(3=)-Ic, bla fosA3, floR, dfrA14, sul1, tetA, aadA1] located in two distinct sites of a megaplasmid (ϳ316 to 323 kb) similar to that described in a bla CTX-M-65 -positive S. Infantis isolate from a patient in Italy. High-quality single nucleotide polymorphism (hqSNP) analysis revealed that all U.S. isolates were closely related, separated by only 1 to 38 pairwise high-quality SNPs, indicating a high likelihood that strains from humans, chickens, and cattle recently evolved from a common ancestor. The U.S. isolates were genetically similar to the bla CTX-M-65 -positive S. Infantis isolate from Italy, with a separation of 34 to 47 SNPs. This is the first report of the bla CTX-M-65 gene and the pESI (plasmid for emerging S. Infantis)-like megaplasmid from S. Infantis in the United States, and it illustrates the importance of applying a global One Health human and animal perspective to combat antimicrobial resistance.