Accurate Neonatal Face Detection for Improved Pain Classification in the Challenging NICU Setting.

There is a tendency for object detection systems using off-the-shelf algorithms to fail when deployed in complex scenes. The present work describes a case for detecting facial expression in post-surgical neonates (newborns) as a modality for predicting and classifying severe pain in the Neonatal Intensive Care Unit (NICU). Our initial testing showed that both an off-the-shelf face detector and a machine learning algorithm trained on adult faces failed to detect facial expression of neonates in the NICU. We improved accuracy in this complex scene by training a state-of-the-art "You-Only-Look-Once" (YOLO) face detection model using the USF-MNPAD-I dataset of neonate faces. At run-time our trained YOLO model showed a difference of 8.6% mean Average Precision (mAP) and 21.2% Area under the ROC Curve (AUC) for automatic classification of neonatal pain compared with manual pain scoring by NICU nurses. Given the challenges, time and effort associated with collecting ground truth from the faces of post-surgical neonates, here we share the weights from training our YOLO model with these facial expression data. These weights can facilitate the further development of accurate strategies for detecting facial expression, which can be used to predict the time to pain onset in combination with other sensory modalities (body movements, crying frequency, vital signs). Reliable predictions of time to pain onset in turn create a therapeutic window of time wherein NICU nurses and providers can implement safe and effective strategies to mitigate severe pain in this vulnerable patient population.

COMT Variants are Associated With Breast and Nipple Pain.

Estimates suggest that only 24.9% of infants born in 2019 were exclusively breastfed before 6 months of age, despite the known health benefits of exclusive breastfeeding. Breast and nipple pain is one of the primary determinants of exclusive breastfeeding. Environmental contributions to breastfeeding success have been reported extensively in the literature, but the contribution(s) of maternal genetics has yet to be discovered. The purpose of the study was to identify an association between pain and lactation-related gene variants with exclusive breastfeeding determinants. We selected 4 genes having single nucleotide polymorphisms (SNPs) with potential functional significance in breastfeeding and pain: prolactin receptor (PRLR), oxytocin receptor (OXTR), catechol-O-methyltransferase (COMT), and milk fat globule epidermal growth factor and factor V/VIII domain containing (MFGE8). We performed a cross-sectional secondary analysis of a longitudinal randomized controlled trial study, Promoting Self-Management of Breast and Nipple Pain with Biomarkers and Technology for Breastfeeding Women (NCT05262920). Breast and nipple pain, perceived insufficient milk, and breastfeeding self-efficacy were examined using total scale scores for the Brief Pain Inventory, Visual Analog Scale, H&H Lactation Scale, and the Breastfeeding Self-efficacy Scale-short form, respectively. Of the candidate genes examined, SNPs within COMT were significantly associated with breastfeeding-related outcomes. Specifically, COMT rs4633 and rs4680 minor allele carriers (T, A) reported higher breast and nipple pain intensity than women homozygous for the major allele (C, G). COMT is the most widely researched "pain gene" and has been linked to cold, postoperative, and postpartum pain. This study is the first to identify a contribution of COMT variants to breast and nipple pain and, as a result, to breastfeeding exclusivity. PERSPECTIVE: Two SNPs in the pain gene COMT are associated with breast and nipple pain. Clinically, a minor allele in COMT rs4633 and rs4680 may increase a woman's rating of moderate breast and nipple pain. TRIAL REGISTRATION: PROMPT was registered in ClinicalTrials.gov (protocol #NCT05262920).

Diabetic Retinopathy during pregnancy in Hispanic women with latent Toxoplasma gondii infection.

BACKGROUND: Retinal photography was performed in pregnancy and postpartum in pregnant Hispanic women with latent Toxoplasma gondii (TG) infection in order to screen for characteristic retinal lesions or the particular scars found in people with active T. gondii infection. A comparison group of TG negative women was included in the study but they did not have retinal photography. OBJECTIVE: The goal of the parent study was to assess for adverse pregnancy events and evidence for parasite reactivation in TG positive (TG + ) women, through examination of the eyes for characteristic lesions. Retinal photography, usually at prenatal visits 2 (17 +/- 3.35 weeks) and 3 (26.3+/-1.75) weeks, was done on TG + women. Fifty-six of these women also (43 %) had retinal photography at the postpartum visit. Health and demographic data were obtained at the first prenatal visit for all women. STUDY DESIGN: From the 690 recruited at the first prenatal visit, 128 TG- women and 158 TG + women were enrolled in a prospective study through pregnancy and the postpartum. All TG- women (n = 532) provided data at the first prenatal visit and throughout their pregnancy and birth through the EHR. This allowed comparison of health and outcome data for the TG + compared to a larger number of TG- Hispanic pregnant women. RESULTS: While there was no evidence of ocular toxoplasmosis during pregnancy, there was a surprisingly large number (42 %) of TG + women with diabetic retinopathy (DR). We also observed that TG + women had a 20 % incidence of gestational diabetes mellitus (GDM) compared to 11.3 % in the TG- women (p = 0.01). At postpartum (mean 5.6 weeks), 23 of 30 women with pregnancy DR showed no DR in the postpartum. CONCLUSIONS: No characteristic T. gondii lesions were discovered. Retinal photography serendipitously revealed DR in these T. gondii positive women. It was also found that latent TG infection was associated with increased incidence of GDM. Hispanic pregnant women's increased risk for latent TG infection, GDM and DR are underappreciated. Retinal photography may need to be considered an innovative approach to screening.

Social Determinants of Health Among Pregnant Hispanic Women and Associated Psychological Outcomes.

BACKGROUND: There has been a concerning surge in maternal mortality among Hispanic women in recent years. Compromised mental health is present in nearly half of all maternal deaths, and risk factors include poor social support and depression. OBJECTIVE: Among Hispanic women who were born in the USA versus those not born in the USA, we sought to describe and compare social determinants of health and maternal psychological outcomes. METHODS: Hispanic pregnant women (n = 579) were recruited from two clinics in Tampa, FL, and completed various questionnaires related to social determinants of health, depression, stress, and social support. STATISTICAL ANALYSIS: Descriptive statistics, t-tests, and chi-square analyses were used to compare relationships between maternal nativity and subsequent psychosocial outcomes. Pearson correlations were used to explore associations between variables. RESULTS: Hispanic pregnant women who were not born in the USA had lower incomes (χ2 = 5.68, p = 0.018, df = 1), were more likely to be unemployed (χ2 = 8.12, p = 0.004, df = 1), and were more likely to be married (χ2 = 4.79, p = 0.029, df = 1) when compared with those born in the USA. Those not born in the USA reported lower social support (t = 3.92, p<0.001), specifically the tangible (t = 4.18, p < 0.001) and emotional support subscales (t = 4.4, p<0.001). When compared with those born in the USA, foreign-born Hispanic women reported less stress (t = 3.23, p = 0.001) and depression (t = 3.3, p = 0.002). CONCLUSION: Pregnant Hispanic women not born in the USA are at increased risk for suboptimal social determinants of health, including less social support. US-born women were more stressed and depressed and had higher BMIs.

The Salivary Microbiome During Pregnancy: Associations With Clinical and Sociodemographic Characteristics.

PURPOSE: Poor oral health has been associated with adverse pregnancy outcomes, and the oral microbiome may play a role in these mechanisms. We aimed to examine the salivary microbiome for alterations in diversity or relative abundance throughout pregnancy and its associations with adverse pregnancy outcomes and sociodemographic characteristics. STUDY DESIGN AND METHODS: We conducted an ancillary study from a previous cohort study of 37 women during their second and third trimesters of pregnancy using preexisting, participant-collected salivary samples to examine the oral microbiome using 16S rRNA sequencing. RESULTS: The salivary microbiome demonstrated stability throughout pregnancy, as there were no significant differences in alpha or beta diversity. Individuals who were diagnosed with preeclampsia had differences in beta diversity at the genus level (F = 2.65, df = 1, P = .015). There were also differences in beta diversity at the species level in Hispanic individuals compared with non-Hispanic individuals (F = 1.7183, df = 1, P = .04). CONCLUSION: The salivary microbiome demonstrated stability throughout the second and third trimesters but may be different in Hispanics or those diagnosed with preeclampsia. As such, clinical providers need to demonstrate culturally competent care during pregnancy and continue to educate women about the importance of oral healthcare during the perinatal period. Future research is needed to examine the mechanisms associated with oral microbiome dysbiosis in Hispanic women during pregnancy and in women with preeclampsia.

Tryptophan metabolism and immune alterations in pregnant Hispanic women with chronic Toxoplasma gondii infection.

PROBLEM: Pregnancy markedly modifies women's metabolism and immune functions. We hypothesized that pregnancy might alter the immune and metabolic responses to chronic Toxoplasma gondii infection in pregnancy. METHOD OF STUDY: A population of 690 pregnant Hispanic women were screened for antibodies to T. gondii and 158 women were positive (23% positivity) with 83% showing high avidity indices. These seropositive women were followed through their pregnancies with four data collection time points and a postpartum collection at two clinics in Tampa, Florida. A T. gondii seronegative group (N = 128) was randomly selected to serve as a control group and measured along pregnancy in the same way. Serum levels of tryptophan, kynurenine, and their ratio, phenylalanine, tyrosine and their ratio, neopterin, and nitrite were measured through pregnancy and the postpartum. A plasma cytokine panel (IFN-γ, TNFα, IL-2, IL-10, IL-12, IL-6, IL-17) was analyzed in parallel. RESULTS: The major findings suggest that indoleamine 2,3-dioxygenase (IDO-1) was less activated in T. gondii seropositive pregnant Hispanic women with chronic infection. Evidence for IDO-1 suppression was that tryptophan catabolism was less pronounced and there were lower levels of multiple inflammatory cytokines including IFN-γ, which is the major inducer of IDO-1, and higher nitrite concentration, a surrogate marker for nitric oxide, an inhibitor of IDO. CONCLUSIONS: Latent T. gondii infection was associated with higher plasma tryptophan levels, and lower inflammatory cytokines across pregnancy, suggesting suppression of the IDO-1 enzyme, and possible T cell exhaustion during pregnancy.

The Oral Microbiome Throughout Pregnancy: A Scoping Review.

INTRODUCTION: Oral health is associated with systemic health, including adverse pregnancy outcomes. Understanding the oral microbiome during pregnancy may lead to targeted interventions for prevention of adverse outcomes. The purpose of this review is to examine the literature on the oral microbiome throughout pregnancy. METHODS: We conducted a literature search with four electronic databases for original research conducted between 2012 and 2022 that examined the oral microbiome longitudinally using 16s rRNA sequencing during pregnancy. RESULTS: We identified six studies that examined the oral microbiome longitudinally throughout pregnancy, though comparisons of oral niches, oral microbiome measures, and findings between studies were not consistent. Three studies identified alterations in alpha diversity throughout pregnancy and two studies identified increased pathogenic bacteria during pregnancy. Three studies reported no changes in the oral microbiome throughout pregnancy, and one study identified differences in the composition of the microbiome based on socioeconomic status and antibiotic exposure. Two studies examined adverse pregnancy outcomes in association with the oral microbiome, one reporting no associations and one reported difference in community gene composition in those diagnosed with preeclampsia. CLINICAL IMPLICATIONS: There is limited research on the composition of the oral microbiome throughout pregnancy. There may be alterations in the oral microbiome during pregnancy such as increased relative abundance of pathogenic bacteria. Socioeconomic status, antibiotic use, and education may contribute to differences in the microbiome composition over time. Clinicians should evaluate oral health and educate on the importance of oral health care during the prenatal and perinatal time period.

Composition of the maternal gastrointestinal microbiome as a predictor of neonatal birth weight.

BACKGROUND: The biological mechanism by which the maternal gastrointestinal microbiota contributes to fetal growth and neonatal birth weight is currently unknown. The purpose of this study was to explore how the composition of the maternal microbiome in varying pre-gravid body mass index (BMI) groups are associated with neonatal birth weight adjusted for gestational age. METHODS: Retrospective, cross-sectional metagenomic analysis of bio-banked fecal swab biospecimens (n = 102) self-collected by participants in the late second trimester of pregnancy. RESULTS: Through high-dimensional regression analysis using principal components (PC) of the microbiome, we found that the best performing multivariate model explained 22.9% of the variation in neonatal weight adjusted for gestational age. Pre-gravid BMI (p = 0.05), PC3 (p = 0.03), and the interaction of the maternal microbiome with maternal blood glucose on the glucose challenge test (p = 0.01) were significant predictors of neonatal birth weight after adjusting for potential confounders including maternal antibiotic use during gestation and total gestational weight gain. CONCLUSIONS: Our results indicate a significant association between the maternal gastrointestinal microbiome in the late second trimester and neonatal birth weight adjusted for gestational age. Moderated by blood glucose at the time of the universal glucose screening, the gastrointestinal microbiome may have a role in the regulation of fetal growth. IMPACT: Maternal blood glucose in the late second trimester significantly moderates the relationship between the maternal gastrointestinal microbiome and neonatal size adjusted for gestational age. Our findings provide preliminary evidence for fetal programming of neonatal birth weight through the maternal gastrointestinal microbiome during pregnancy.

The Human Milk Metabolome: A Scoping Literature Review.

BACKGROUND: Human milk is a complex source of nutrition and other bioactives that protects infants from disease, holding a lifetime of beneficial effects. The field of metabolomics provides a robust platform through which we can better understand human milk at a level rarely examined. RESEARCH AIM: To Identify, describe, synthesize, and critically analyze the literature within the past 5 years related to the human milk metabolome. METHODS: We conducted a scoping literature review and quality analysis of the recent science reflecting untargeted metabolomic approaches to examining human milk. We searched six databases using the terms "breast milk," "metabolome," "metabolite," and "human milk," Out of more than 1,069 abstracts, we screened and identified 22 articles that met our inclusion criteria. RESULTS: We extracted data related to the study author, geographic location, research design, analyses, platform used, and results. We also extracted data related to human milk research activities, including collection protocol, infant/maternal considerations, and time. Selected studies focused on a variety of phenotypes, including maternal and infant disease. Investigators used varying approaches to evaluate the metabolome, and differing milk collection protocols were observed. CONCLUSION: The human milk metabolome is informed by many factors-which may contribute to infant health outcomes-that have resulted in disparate milk metabolomic profiles. Standardized milk collection and storage procedures should be implemented to minimize degradation. Investigators may use our findings to develop research questions that test a targeted metabolomic approach.

Metagenomic characterization of the maternal prenatal gastrointestinal microbiome by pregravid BMI.

OBJECTIVE: The incidence of women entering into pregnancy with BMI indicating overweight or obesity is rising with concurrent increases in adverse complications such as gestational diabetes. Although several studies have examined the compositional changes to the microbiome across BMI classifications, there has been no investigation regarding changes in microbial function during pregnancy. METHODS: A total of 105 gastrointestinal microbiome biospecimens were used in this analysis. Biospecimens were sequenced by using the Illumina NovaSeq 6000 shotgun metagenomics platform. RESULTS: Findings indicate an enrichment in microbiota from the phylum Firmicutes across all pregravid BMI groups with a decrease in α diversity in groups with BMI indicating obesity or overweight compared with a group with BMI indicating normal weight (p = 0.02). More specifically, women with BMI indicating obesity or overweight had enrichment in Bifidobacterium bifidum and B. adolescentis. Women with BMI > 25 kg/m2 had a higher abundance of microbiota that support biotin synthesis and regulate epithelial cells in the lower gastrointestinal tract. These epithelial cells are responsible for host adaptability to dietary lipid variation and caloric absorption. CONCLUSIONS: Our analysis suggests that there are differences in microbial composition and function between BMI groups. Future research should consider how these changes contribute to specific clinical outcomes during pregnancy.

Adverse pregnancy outcomes in Toxoplasma gondii seropositive Hispanic women.

AIMS: Chronic Toxoplasma gondii infection is not thought to affect pregnancy or birth outcomes, but there are few prospective studies. The study aims were T. gondii immunoglobulin G measurement and relationship of chronic T. gondii infection with gestational age at birth and adverse pregnancy outcomes in 690 Hispanic women in Tampa, Florida. METHODS: Hispanic women, born either in the United States or in Latin America or the Caribbean had a venous blood sample drawn to measure T. gondii IgG and T. gondii serotype at the first prenatal visit, along with collection of demographic and health-related measures. Seropositive and seronegative women were followed throughout their pregnancy. Gestational age, infant weights, and adverse pregnancy outcomes (miscarriages, preterm births) were compared in the two groups. RESULTS: There were 740 women of self-reported Hispanic ethnicity screened and enrolled in Tampa, Florida, with 690 having birth data extracted from the electronic health record (538 T. gondii negative and 152 T. gondii seropositive). T. gondii seropositivity was 22.4% and the majority (83%) had high avidity titers, indicating chronic infection. Compared to T. gondii seronegative Hispanic women, seroseropositive women had more smaller for gestational age infants and higher prevalences of miscarriages and preterm birth. CONCLUSION: This is one of the largest longitudinal cohort studies of women with chronic T. gondii infection followed through pregnancy. There was a higher percentages of adverse pregnancy outcomes in this group compared to T. gondii seronegative controls. The mechanism for this is unknown and warrants reexamination of the dogma that chronic T. gondii infection in pregnant women has no significant clinical consequences.

A framework to guide research and practice response to emerging infectious diseases: Genomic-to-global considerations.

Newly emerging infectious diseases (EIDs), like the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, are becoming increasingly common. Due to geographic, political, social, behavioral, and genomic differences, some populations are more vulnerable to infectious disease spread than others. The purpose of this article is to present a framework for research and practice response to emergent infectious diseases that addresses multiple transdisciplinary actions to limit exposure or mitigate adverse outcomes for individuals and communities. Recent experience with new strains of emergent infectious diseases reinforces the importance of intervening at multiple levels, from genomics to political messaging to create multipronged, transdisciplinary interventions to contain the threat. In particular, incorporation of genomics into public health nursing practice of infectious diseases management can enhance existing regional-, community-, and individual-level health promotion and protection efforts, thus impacting long-term health outcomes.

Association between microbial composition, diversity, and function of the maternal gastrointestinal microbiome with impaired glucose tolerance on the glucose challenge test.

Over the last two decades, the incidence of gestational diabetes (GDM) has almost doubled resulting in almost 9% of pregnant women diagnosed with GDM. Occurring more frequently than GDM is impaired glucose tolerance (IGT), also known as pre-diabetes, but it has been understudied during pregnancy resulting in a lack of clinical recommendations of maternal and fetal surveillance. The purpose of this retrospective, cross-sectional study was to examine the association between microbial diversity and function of the maternal microbiome with IGT while adjusting for confounding variables. We hypothesized that reduced maternal microbial diversity and increased gene abundance for insulin resistance function will be associated with IGT as defined by a value greater than 140 mg/dL on the glucose challenge test. In the examination of microbial composition between women with IGT and those with normal glucose tolerance (NGT), we found five taxa which were significantly different. Taxa higher in participants with impaired glucose tolerance were Ruminococcacea (p = 0.01), Schaalia turicensis (p<0.05), Oscillibacter (p = 0.03), Oscillospiraceae (p = 0.02), and Methanobrevibacter smithii (p = 0.04). When we further compare participants who have IGT by their pre-gravid BMI, five taxa are significantly different between the BMI groups, Enterobacteriaceae, Dialister micraerophilus, Campylobacter ureolyticus, Proteobacteria, Streptococcus Unclassified (species). All four metrics including the Shannon (p<0.00), Simpson (p<0.00), Inverse Simpson (p = 0.04), and Chao1 (p = 0.04), showed a significant difference in alpha diversity with increased values in the impaired glucose tolerance group. Our study highlights the important gastrointestinal microbiome changes in women with IGT during pregnancy. Understanding the role of the microbiome in regulating glucose tolerance during pregnancy helps clinicians and researchers to understand the importance of IGT as a marker for adverse maternal and neonatal outcomes.

Relationships of the very low birth weight infant microbiome with neurodevelopment at 2 and 4 years of age.

Very low birth weight (VLBW) infants (<1500 g) are at risk for poor neurodevelopmental outcomes depending on gestational age (GA), birth weight (BW), and morbidity in early life. The contribution of the gut microbiome is not well understood. Stool samples were collected weekly in the neonatal intensive care unit (NICU) from 24 VLBW infants for 6 weeks after admission and then again at 2 and 4 years of age. The Battelle Development Inventory-2 Screening Test (BDI-2 ST) was administered at 2- and 4-year time points. VLBW infants had dysbiotic microbiota in the NICU that progressed for most to an adult-type microbiota by 4 years of age. The BDI-2 ST results at age of 2 years triggered referral for further testing in 14 toddlers (70%), and by 4 years of age only seven of these 14 continued to require referral. Both NICU infant stool diversity and particular microbial amplicon sequence variants were associated with BDI-2 ST subscales, particularly for cognition, adaptive, and communication subscales, when controlled for GA, BW, and antibiotic exposure. Network analysis of the NICU infant stool microbial ecology showed differences in children needing neurodevelopmental referral. The results of this preliminary study indicate that the neonatal gut microbiome plays a role in early cognitive and behavioral neurodevelopment.

Scoping Review of the Relationship Between Gestational Diabetes Mellitus and the Neonatal and Infant Gut Microbiome.

OBJECTIVE: To conduct a scoping review to examine the relationship between a diagnosis of gestational diabetes mellitus (GDM) and the neonatal and infant gut microbiome from 0 to 1 year of age. DATA SOURCES: We searched PubMed, Scopus, Embase, and CINAHL for articles with key terms "microbiome" and "gestational diabetes mellitus." STUDY SELECTION: We included articles published in English in peer-reviewed journals between 2012 and 2021 that were reports of original research studies in which researchers used next-generation sequencing for analysis of the fecal microbiome and collected meconium or transitional stool from neonates and/or infants. DATA EXTRACTION: We identified nine studies with a combined sample size of 1,279 neonates and infants. We extracted data, including title, authors, sample size, study design, methods, findings, significance, and limitations. We extracted and charted confounding variables such as treatment of GDM, body mass index, gestational age at birth, antibiotic use, mode of birth, and feeding method. DATA SYNTHESIS: Gestational diabetes mellitus may alter the neonatal and infant gut microbiome because neonates and infants of women with GDM had altered composition and diversity compared to neonates and infants of women without GDM. CONCLUSION: Mechanisms by which the neonatal and infant microbiome changes in response to GDM are poorly understood and need to be evaluated in future research. Further study of how GDM plays a role in the initial seeding of the microbiome, how the maternal microbiome may affect fetal metabolic programming, and how the neonatal microbiome leads to the future development of obesity and glucose intolerance is critical. Future studies should include larger sample sizes, appropriate collection of potential confounding variables, assessment of maternal interventions for GDM, and longitudinal designs to further understand potential associations with long-term detrimental outcomes such as obesity and impaired glucose tolerance.

Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1.

Ample evidence indicates that the gut microbiome is a tumor-extrinsic factor associated with antitumor response to anti-programmed cell death protein-1 (PD-1) therapy, but inconsistencies exist between published microbial signatures associated with clinical outcomes. To resolve this, we evaluated a new melanoma cohort, along with four published datasets. Time-to-event analysis showed that baseline microbiota composition was optimally associated with clinical outcome at approximately 1 year after initiation of treatment. Meta-analysis and other bioinformatic analyses of the combined data show that bacteria associated with favorable response are confined within the Actinobacteria phylum and the Lachnospiraceae/Ruminococcaceae families of Firmicutes. Conversely, Gram-negative bacteria were associated with an inflammatory host intestinal gene signature, increased blood neutrophil-to-lymphocyte ratio, and unfavorable outcome. Two microbial signatures, enriched for Lachnospiraceae spp. and Streptococcaceae spp., were associated with favorable and unfavorable clinical response, respectively, and with distinct immune-related adverse effects. Despite between-cohort heterogeneity, optimized all-minus-one supervised learning algorithms trained on batch-corrected microbiome data consistently predicted outcomes to programmed cell death protein-1 therapy in all cohorts. Gut microbial communities (microbiotypes) with nonuniform geographical distribution were associated with favorable and unfavorable outcomes, contributing to discrepancies between cohorts. Our findings shed new light on the complex interaction between the gut microbiome and response to cancer immunotherapy, providing a roadmap for future studies.

Neonatal pain assessment: Do we have the right tools?

Background: The assessment and management of neonatal pain is crucial for the development and wellbeing of vulnerable infants. Specifically, neonatal pain is associated with adverse health outcomes but is often under-identified and therefore under-treated. Neonatal stress may be misinterpreted as pain and may therefore be treated inappropriately. The assessment of neonatal pain is complicated by the non-verbal status of patients, age-dependent variation in pain responses, limited education on identifying pain in premature infants, and the clinical utility of existing tools. Objective: We review research surrounding neonatal pain assessment scales currently in use to assess neonatal pain in the neonatal intensive care unit. Methods: We performed a systematic review of original research using PRISMA guidelines for literature published between 2016 and 2021 using the key words "neonatal pain assessment" in the databases Web of Science, PubMed, and CINAHL. Fifteen articles remained after review, duplicate, irrelevant, or low-quality articles were eliminated. Results: We found research evaluating 13 neonatal pain scales. Important measurement categories include behavioral parameters, physiological parameters, continuous pain, acute pain, chronic pain, and the ability to distinguish between pain and stress. Provider education, inter-rater reliability and ease of use are important factors that contribute to an assessment tool's success. Each scale studied had strengths and limitations that aided or hindered its use for measuring neonatal pain in the neonatal intensive care unit, but no scale excelled in all areas identified as important for reliably identifying and measuring pain in this vulnerable population. Conclusion: A more comprehensive neonatal pain assessment tool and more provider education on differences in pain signals in premature neonates may be needed to increase the clinical utility of pain scales that address the different aspects of neonatal pain.

Attentional Generative Multimodal Network for Neonatal Postoperative Pain Estimation.

Artificial Intelligence (AI)-based methods allow for automatic assessment of pain intensity based on continuous monitoring and processing of subtle changes in sensory signals, including facial expression, body movements, and crying frequency. Currently, there is a large and growing need for expanding current AI-based approaches to the assessment of postoperative pain in the neonatal intensive care unit (NICU). In contrast to acute procedural pain in the clinic, the NICU has neonates emerging from postoperative sedation, usually intubated, and with variable energy reserves for manifesting forceful pain responses. Here, we present a novel multi-modal approach designed, developed, and validated for assessment of neonatal postoperative pain in the challenging NICU setting. Our approach includes a robust network capable of efficient reconstruction of missing modalities (e.g., obscured facial expression due to intubation) using an unsupervised spatio-temporal feature learning with a generative model for learning the joint features. Our approach generates the final pain score along with the intensity using an attentional cross-modal feature fusion. Using experimental dataset from postoperative neonates in the NICU, our pain assessment approach achieves superior performance (AUC 0.906, accuracy 0.820) as compared to the state-of-the-art approaches.

Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients.

Anti-programmed cell death protein 1 (PD-1) therapy provides long-term clinical benefits to patients with advanced melanoma. The composition of the gut microbiota correlates with anti-PD-1 efficacy in preclinical models and cancer patients. To investigate whether resistance to anti-PD-1 can be overcome by changing the gut microbiota, this clinical trial evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti-PD-1 in patients with PD-1-refractory melanoma. This combination was well tolerated, provided clinical benefit in 6 of 15 patients, and induced rapid and durable microbiota perturbation. Responders exhibited increased abundance of taxa that were previously shown to be associated with response to anti-PD-1, increased CD8+ T cell activation, and decreased frequency of interleukin-8-expressing myeloid cells. Responders had distinct proteomic and metabolomic signatures, and transkingdom network analyses confirmed that the gut microbiome regulated these changes. Collectively, our findings show that FMT and anti-PD-1 changed the gut microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti-PD-1 in a subset of PD-1 advanced melanoma.

Metabolic and Microbial Changes Associated With Diet and Obesity During Pregnancy: What Can We Learn From Animal Studies?

The intestinal microbiota changes throughout pregnancy and influences maternal metabolic adaptations to support fetal growth. Obesity induces alterations to the microbiota that include decreased microbial diversity and shifts in microbial composition, though specific species changes are inconsistent between published studies. In animal models, probiotics and exercise moderate maternal weight gain and partially correct the maternal microbiota. Supplemental Escherichia coli, however, exacerbate maternal obesity during the perinatal period, lending weight to the theory that inflammation-induced gut epithelial barrier leak influences metabolic dysregulation. Although birth weight is not always altered when offspring are exposed to an obesogenic diet during gestation, insulin resistance and lipid metabolism are impacted through adulthood in association with this exposure and can lead to increased body weight in adulthood. Postnatal offspring growth is accelerated in response to maternal overnutrition during lactation. Offspring microbiota, metabolism, and behavior are altered in response to early exposure to high fat and high sucrose diets. Consequences to this exposure include impaired glucose and insulin homeostasis, fatty liver, and neurobehavioral deficits that can be ameliorated by improving the microbial environment. In this mini review, we provide an overview of the use of translational animal models to understand the mechanisms associated with changes to the gastrointestinal microbiota due to maternal obesity and the microbial impact on the metabolic changes of pregnancy.