Metabolism-Disrupting Chemical Mixtures during Pregnancy, Folic Acid Supplementation, and Liver Injury in Mother-Child Pairs.

Background and Aims: Scarce knowledge about the impact of metabolism-disrupting chemicals (MDCs) on liver injury limits opportunities for intervention. We evaluated pregnancy MDC-mixture associations with liver injury and effect modification by folic acid (FA) supplementation in mother-child pairs. Methods: We studied ∼200 mother-child pairs from the Mexican PROGRESS cohort, with measured 43 MDCs during pregnancy (estimated air pollutants, blood/urine metals or metalloids, urine high- and low-molecular-weight phthalate [HMWPs, LMWPs] and organophosphate-pesticide [OP] metabolites), and serum liver enzymes (ALT, AST) at ∼9 years post-parturition. We defined liver injury as elevated liver enzymes in children, and using established clinical scores for steatosis and fibrosis in mothers (i.e., AST:ALT, FLI, HSI, FIB-4). Bayesian Weighted Quantile Sum regression assessed MDC-mixture associations with liver injury outcomes. We further examined chemical-chemical interactions and effect modification by self-reported FA supplementation. Results: In children, many MDC-mixtures were associated with liver injury outcomes. Per quartile HMWP-mixture increase, ALT increased by 10.1% (95%CI: 1.67%, 19.4%) and AST by 5.27% (95% CI: 0.80%, 10.1%). LMWP-mixtures and air pollutant-mixtures were associated with higher AST and ALT, respectively. Air pollutant and non-essential metal/element associations with liver enzymes were attenuated by maternal cobalt blood concentrations ( p -interactions<0.05). In mothers, only the LMWP-mixture was associated with liver injury [OR=1.53 (95%CI: 1.01, 2.28) for HSI>36, and OR=1.62 (95%CI: 1.05, 2.49) for AST:ALT<1]. In mothers and children, most associations were attenuated (null) at FA supplementation≥600mcg/day ( p -interactions<0.05). Conclusions: Pregnancy MDC exposures may increase liver injury risk, particularly in children. These associations may be attenuated by higher FA supplementation and maternal cobalt levels.

Current practice for the chemical immobilisation of non-domestic feline species: An online survey study.

BACKGROUND: Safe chemical immobilisation of wild felids is essential for both conservational management and clinical purposes. However, little is known about drug protocols and current practice. METHODS: This study was designed as an online survey based on a questionnaire. Descriptive/correlation statistics and analysis of proportions were used for data analysis. RESULTS: The preferred immobilisation technique was the use of darts (37% of the respondents), while the most popular drug combination was a mixture of benzodiazepines, alpha-2 adrenoreceptor agonists and dissociative anaesthetics (27%). The inclusion of ketamine in the drug mixture was associated with a quicker anaesthetic onset, as estimated by the participants (p < 0.001). Common complications were prolonged recovery (46%), bradycardia (35%), hypoventilation (32%), hypothermia (26%) and arousal (26%). Commonly encountered problems were inappropriate equipment (39%), lack of suitable drugs (27%) and inadequate knowledge of species-specific pharmacology (29%) and physiology (24%). LIMITATIONS: Incomplete adherence to the Checklist for Reporting Results of Internet E-Surveys is acknowledged. CONCLUSIONS: Drug protocols including both alpha-2 adrenoreceptor agonists and dissociative anaesthetics are preferred in wild felids, and the inclusion of ketamine may be useful to achieve a quick onset. Equipment/drug availability and species-specific knowledge are potential areas of improvement to improve wild felid anaesthesia.

Evaluation of Black Soldier Fly Hermetia illucens as Food for Pink-Spotted Lady Beetle Coleomegilla maculata.

The discovery of new and improved factitious and artificial diets is necessary for cost-effective rearing of predatory arthropods. This study evaluated Hermetia illucens black soldier fly (BSF) as a suitable alternative food source for rearing the predatory coccinellid Coleomegilla maculata (Cmac). The hypothesis that BSF larval powder was suitable food to support the growth, development, and reproduction of Cmac was tested in the laboratory. When compared to a standard in-house diet containing brine shrimp egg powder plus Chlorella vulgaris green algae and myristic acid (BSE+CM), the BSF and BSF+CM diets reduced immature growth and development. Immatures successfully reared to teneral adults were smaller when fed BSF or BSF+CM rather than BSE+CM. Combining BSF with a powdered artificial diet (AD), i.e., BSF+AD, did not improve predator growth or development, compared to Cmac reared on BSE+CM. Cmac oviposition responses, i.e., egg clutch production, to BSF vs. BSE+CM or BSF+AD vs. BSE+CM did not differ significantly. In conclusion, BSF has the potential to be food that supports Cmac oviposition behavior. Future research is necessary to discover an ideal mixture of BSF, BSE+CM, or AD that supports Cmac growth, development, and reproduction over multiple generations.

PFAS Exposures and the Human Metabolome: A Systematic Review of Epidemiological Studies.

Purpose of Review: There is a growing interest in understanding the health effects of exposure to per- and polyfluoroalkyl substances (PFAS) through the study of the human metabolome. In this systematic review, we aimed to identify consistent findings between PFAS and metabolomic signatures. We conducted a search matching specific keywords that was independently reviewed by two authors on two databases (EMBASE and PubMed) from their inception through July 19, 2022 following PRISMA guidelines. Recent Findings: We identified a total of 28 eligible observational studies that evaluated the associations between 31 different PFAS exposures and metabolomics in humans. The most common exposure evaluated was legacy long-chain PFAS. Population sample sizes ranged from 40 to 1,105 participants at different stages across the lifespan. A total of 19 studies used a non-targeted metabolomics approach, 7 used targeted approaches, and 2 included both. The majority of studies were cross-sectional (n = 25), including four with prospective analyses of PFAS measured prior to metabolomics. Summary: Most frequently reported associations across studies were observed between PFAS and amino acids, fatty acids, glycerophospholipids, glycerolipids, phosphosphingolipids, bile acids, ceramides, purines, and acylcarnitines. Corresponding metabolic pathways were also altered, including lipid, amino acid, carbohydrate, nucleotide, energy metabolism, glycan biosynthesis and metabolism, and metabolism of cofactors and vitamins. We found consistent evidence across studies indicating PFAS-induced alterations in lipid and amino acid metabolites, which may be involved in energy and cell membrane disruption.

Urine-mediated suppression of Klebsiella pneumoniae mucoidy is counteracted by spontaneous Wzc variants altering capsule chain length.

Klebsiella pneumoniae is a hospital-associated pathogen primarily causing urinary tract infections (UTIs), pneumonia, and septicemia. Two challenging lineages include the hypervirulent strains, causing invasive community-acquired infections, and the carbapenem-resistant classical strains, most frequently isolated from UTIs. While hypervirulent strains are often characterized by a hypermucoid phenotype, classical strains usually present with low mucoidy. Since clinical UTI isolates tend to exhibit limited mucoidy, we hypothesized that environmental conditions may drive K. pneumoniae adaptation to the urinary tract and select against mucoid isolates. We found that both hypervirulent K. pneumoniae and classical Klebsiella UTI isolates significantly suppressed mucoidy when cultured in urine without reducing capsule abundance. A genetic screen identified secondary mutations in the wzc tyrosine kinase that overcome urine-suppressed mucoidy. Over-expressing Wzc variants in trans was sufficient to boost mucoidy in both hypervirulent and classical Klebsiella UTI isolates. Wzc is a bacterial tyrosine kinase that regulates capsule polymerization and extrusion. Although some Wzc variants reduced Wzc phospho-status, urine did not alter Wzc phospho-status. Urine does, however, increase K. pneumoniae capsule chain length diversity and enhance cell-surface attachment. The identified Wzc variants counteract urine-mediated effects on capsule chain length and cell attachment. Combined, these data indicate that capsule chain length correlates with K. pneumoniae mucoidy and that this extracellular feature can be fine-tuned by spontaneous Wzc mutations, which alter host interactions. Spontaneous Wzc mutation represents a global mechanism that could fine-tune K. pneumoniae niche-specific fitness in both classical and hypervirulent isolates. IMPORTANCE Klebsiella pneumoniae is high-priority pathogen causing both hospital-associated infections, such as urinary tract infections, and community-acquired infections. Clinical isolates from community-acquired infection are often characterized by a tacky, hypermucoid phenotype, while urinary tract isolates are usually not mucoid. Historically, mucoidy was attributed to capsule overproduction; however, recent reports have demonstrated that K. pneumoniae capsule abundance and mucoidy are not always correlated. Here, we report that human urine suppresses K. pneumoniae mucoidy, diversifies capsule polysaccharide chain length, and increases cell surface association. Moreover, specific mutations in the capsule biosynthesis gene, wzc, are sufficient to overcome urine-mediated suppression of mucoidy. These Wzc variants cause constitutive production of more uniform capsular polysaccharide chains and increased release of capsule from the cell surface, even in urine. These data demonstrate that K. pneumoniae regulates capsule chain length and cell surface attachment in response host cues, which can alter bacteria-host interactions.

Discrepancy between predicted and measured exercise intensity for eliciting the maximal rate of lipid oxidation.

BACKGROUND AND AIMS: Ectopic lipid storage is implicated in type 2 diabetes pathogenesis; hence, exercise to deplete stores (i.e., at the intensity that allows for maximal rate of lipid oxidation; MLO) might be optimal for restoring metabolic health. This intensity ("Fatmax") is estimated during incremental exercise ("Fatmax test"). However, in "the field" general recommendations exist regarding a range of percentages of maximal heart rate (HR) to elicit MLO. The degree to which this range is aligned with measured Fatmax has not been investigated. We compared measured HR at Fatmax, with maximal HR percentages within the typically recommended range in a sample of 26 individuals (Female: n = 11, European ancestry: n = 17). METHODS AND RESULTS: Subjects completed a modified Fatmax test with a 5-min warmup, followed by incremental stages starting at 15 W with work rate increased by 15 W every 5 min until termination criteria were reached. Pulmonary gas exchange was recorded and average values for V˙ o2 and V˙ co2 for the final minute of each stage were used to estimate substrate-oxidation rates. We modeled lipid-oxidation kinetics using a sinusoidal model and expressed MLO relative to peak V˙ o2 and HR. Bland-Altman analysis demonstrated lack of concordance between HR at Fatmax and at 50%, 70%, and 80% of age-predicted maximum with a mean difference of 23 b·min-1. CONCLUSION: Our results indicate that estimated "fat-burning" heart rate zones are inappropriate for prescribing exercise to elicit MLO and we recommend direct individual exercise lipid oxidation measurements to elicit these values.

Prenatal lead exposure is negatively associated with the gut microbiome in childhood.

Background: Metal exposures are associated with gut microbiome (GM) composition and function, and exposures early in development may be particularly important. Considering the role of the GM in association with many adverse health outcomes, understanding the relationship between prenatal metal exposures and the GM is critically important. However, there is sparse knowledge of the association between prenatal metal exposure and GM later in childhood. Objectives: This analysis aims to identify associations between prenatal lead (Pb) exposure and GM composition and function in children 9-11 years old. Methods: Data come from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort based in Mexico City, Mexico. Prenatal metal concentrations were measured in maternal whole blood drawn during the second and third trimesters of pregnancy. Stool samples collected at 9-11 years old underwent metagenomic sequencing to assess the GM. This analysis uses multiple statistical modeling approaches, including linear regression, permutational analysis of variance, weighted quantile sum regression (WQS), and individual taxa regressions, to estimate the association between maternal blood Pb during pregnancy and multiple aspects of the child GM at 9-11 years old, adjusting for relevant confounders. Results: Of the 123 child participants in this pilot data analysis, 74 were male and 49 were female. Mean prenatal maternal blood Pb was 33.6 (SE = 2.1) ug/L and 34.9 (SE = 2.1) ug/L at second and third trimesters, respectively. Analysis suggests a consistent negative relationship between prenatal maternal blood Pb and the GM at age 9-11, including measures of alpha and beta diversity, microbiome mixture analysis, and individual taxa. The WQS analysis showed a negative association between prenatal Pb exposure and the gut microbiome, for both second and third trimester exposures (2Tß = -0.17, 95%CI = [-0.46,0.11]; 3Tß = -0.17, 95%CI = [-0.44,0.10]). Ruminococcus gnavus, Bifidobacterium longum, Alistipes indistinctus, Bacteroides caccae, and Bifidobacterium bifidum all had weights above the importance threshold from 80% or more of the WQS repeated holdouts in association with both second and third trimester Pb exposure. Discussion: Pilot data analysis suggests a negative association between prenatal Pb exposure and the gut microbiome later in childhood; however, additional investigation is needed.

Prenatal Lead Exposure is Negatively Associated with the Gut Microbiome in Childhood.

Background: Metal exposures are associated with gut microbiome (GM) composition and function, and exposures early in development may be particularly important. Considering the role of the GM in association with many adverse health outcomes, understanding the relationship between prenatal metal exposures and the GM is critically important. However, there is sparse knowledge of the association between prenatal metal exposure and GM later in childhood. Objectives: This analysis aims to identify associations between prenatal lead (Pb) exposure and GM composition and function in children 9-11 years old. Methods: Data come from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort based in Mexico City, Mexico. Prenatal metal concentrations were measured in maternal whole blood drawn during the second and third trimesters of pregnancy. Stool samples collected at 9-11 years old underwent metagenomic sequencing to assess the GM. This analysis uses multiple statistical modeling approaches, including linear regression, permutational analysis of variance, weighted quantile sum regression (WQS), and individual taxa regressions, to estimate the association between maternal blood Pb during pregnancy and multiple aspects of the child GM at 9-11 years old, adjusting for relevant confounders. Results: Of the 123 child participants in this pilot data analysis, 74 were male and 49 were female. Mean prenatal maternal blood Pb was 33.6(SE=2.1) ug/L and 34.9(SE=2.1) ug/L at second and third trimesters, respectively. Analysis suggests a consistent negative relationship between prenatal maternal blood Pb and the GM at age 9-11, including measures of alpha and beta diversity, microbiome mixture analysis, and individual taxa. The WQS analysis showed a negative association between prenatal Pb exposure and the gut microbiome, for both second and third trimester exposures (2Tß=-0.17,95%CI=[-0.46,0.11]; 3Tß=-0.17,95%CI=[-0.44,0.10]). Ruminococcus gnavus, Bifidobacterium longum, Alistipes indistinctus, Bacteroides caccae, and Bifidobacterium bifidum all had weights above the importance threshold from 80% or more of the WQS repeated holdouts in association with both second and third trimester Pb exposure. Discussion: Pilot data analysis suggests a negative association between prenatal Pb exposure and the gut microbiome later in childhood; however, additional investigation is needed.

Incorporating Public Health Competencies into Veterinary Medical Education.

This study evaluates the success of secondary public health education in enhancing a professional degree in veterinary medicine. Dual-degree programs promote multidisciplinary skill attainment crucial to succeed in today's One Health-centered veterinary workforce. Participant demographics were collected including academic background, dual-degree enrollment status, and intended course of study. Survey data were collected from both Master of Public Health students and dual Doctor of Veterinary Medicine/Master of Public Health students. To measure knowledge attainment, students over a 10-year period were provided core competency and program perception-based surveys upon entering and exiting the public health program. Participants were asked to rate their knowledge of competencies based on a scale of having "no knowledge" to being "very knowledgeable." Program perceptions were reported through multiple response types. Open-ended response questions evaluated participants' perceived program success in aiding the development of professional veterinary public health knowledge. The dual nature of this degree program is hypothesized to enhance interprofessional capabilities for those entering the field of veterinary medicine. A qualitative thematic comparison of participants' entrance and exit survey responses indicated increased levels of concern for career preparation services in dual-degree students. By coursework completion, students' most valued competencies were related to epidemiology, biostatistics, and behavioral health. Quantitative analysis revealed that students concurrently enrolled in a veterinary and public health program demonstrate significantly higher levels of self-reported knowledge relating to disease measurement, ethical and legal principles, and epidemiological data interpretation. Students with educational backgrounds in veterinary and animal sciences demonstrated significantly higher levels of program satisfaction.

Functional substitutions of amino acids that differ between GDF11 and GDF8 impact skeletal development and skeletal muscle.

Growth differentiation factor 11 (GDF11) and GDF8 (MSTN) are closely related TGF-ß family proteins that interact with nearly identical signaling receptors and antagonists. However, GDF11 appears to activate SMAD2/3 more potently than GDF8 in vitro and in vivo. The ligands possess divergent structural properties, whereby substituting unique GDF11 amino acids into GDF8 enhanced the activity of the resulting chimeric GDF8. We investigated potentially distinct endogenous activities of GDF11 and GDF8 in vivo by genetically modifying their mature signaling domains. Full recoding of GDF8 to that of GDF11 yielded mice lacking GDF8, with GDF11 levels ∼50-fold higher than normal, and exhibiting modestly decreased muscle mass, with no apparent negative impacts on health or survival. Substitution of two specific amino acids in the fingertip region of GDF11 with the corresponding GDF8 residues resulted in prenatal axial skeletal transformations, consistent with Gdf11-deficient mice, without apparent perturbation of skeletal or cardiac muscle development or homeostasis. These experiments uncover distinctive features between the GDF11 and GDF8 mature domains in vivo and identify a specific requirement for GDF11 in early-stage skeletal development.

GDF11 and aging biology - controversies resolved and pending.

Since the exogenous administration of GDF11, a TGF-ß superfamily member, was reported to have beneficial effects in some models of human disease, there have been many research studies in GDF11 biology. However, many studies have now confirmed that exogenous administration of GDF11 can improve physiology in disease models, including cardiac fibrosis, experimental stroke, and disordered metabolism. GDF11 is similar to GDF8 (also called Myostatin), differing only by 11 amino acids in their mature signaling domains. These two proteins are now known to be biochemically different both in vitro and in vivo. GDF11 is much more potent than GDF8 and induces more strongly SMAD2 phosphorylation in the myocardium compared to GDF8. GDF8 and GDF11 prodomain are only 52% identical and are cleaved by different Tolloid proteases to liberate the mature signaling domain from inhibition of the prodomain. Here, we review the state of GDF11 biology, highlighting both resolved and remaining controversies.

Factors Affecting Domiciliary Non-Invasive Ventilation Compliance.

Few international studies have investigated factors affecting domiciliary non-invasive ventilation (D-NIV) compliance, and data from the UK are limited. We assessed compliance (defined as ≥ 4 h/night for at least 70% of the time) in a retrospective UK population study, at three time points (0-1 month, 3-4 months and 11-12 months), for all patients commenced on D-NIV over a 5-year period. A total of 359 patients were included. Non-compliant vs. compliant patients were significantly younger (median age 64 (IQR 52-72) vs. 67 (58-75) years, p = 0.032) and more likely to have schizophrenia, consistent at both 3-4 months (5% vs. 1%, p = 0.033) and 11-12 months (5% vs. 2%, p = 0.049). Repeated measures ANOVA demonstrated that the minutes [median (IQR)] of D-NIV used significantly increased at the three time points (0-1 month, 3-4 months and 11-12 months) for patients with hypertension [310 (147.5-431) vs. 341 (89-450) vs. 378 (224.5-477.5), p = 0.003]; diabetes [296.5 (132.5-417.5) vs. 342.5 (94.5-438.5) vs. 382 (247.5-476.25), p = 0.002] and heart failure [293 (177-403) vs. 326 (123-398) vs. 365 (212-493), p = 0.04]. In conclusion, younger and comorbid schizophrenic patients have lower D-NIV compliance rates, and our data suggest that persistence with D-NIV over a year may improve overall use.

Self-reported periodontitis and C-reactive protein in Parkinson's disease: a cross-sectional study of two American cohorts.

Periodontitis triggers systemic repercussions, such as elevated levels of high-sensitive C-reactive protein (hs-CRP). This has never been studied within Parkinson's Disease (PD). The aim of this study is to compare hs-CRP levels of self-reported periodontitis cases versus cases without periodontitis in PD patients. Data from the National Health and Nutrition Examination Survey (2015-2016 and 2017-2018 waves) were analyzed. PD cases were identified through medication regimens and periodontitis cases through a validated self-report questionnaire. 51 participants were included (24 females, 27 males, with mean age of 62.96 (14.71)). While the self-reported periodontitis group presented elevated levels of circulating hs-CRP (5.36 vs. 1.99 mg/L, p = 0.031), the self-reported without periodontitis group presented higher lymphocyte levels (29.35 vs. 28.03%, p = 0.007). Blood levels of hs-CRP were significantly higher in PD cases with self-reported periodontitis. Apart from the lymphocyte levels, there were no other significant differences according to the self-reported periodontal status. Future studies shall explore this association using clinical measures.

High Fructose Intake Contributes to Elevated Diastolic Blood Pressure in Adolescent Girls: Results from The HELENA Study.

BACKGROUND: The association between high fructose consumption and elevated blood pressure continues to be controversial, especially in adolescence. The aim of this study was to assess the association between fructose consumption and elevated blood pressure in an European adolescent population. METHODS: A total of 1733 adolescents (mean ± SD age: 14.7 ± 1.2; percentage of girls: 52.8%) were analysed from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study in eight European countries. Blood pressure was measured using validated devices and methods for measuring systolic blood pressure (SBP) and diastolic blood pressure (DBP). Dietary data were recorded via repeated 24 h recalls (using specifically developed HELENA-DIAT software) and converted into pure fructose (monosaccharide form) and total fructose exposure (pure fructose + fructose from sucrose) intake using a specific fructose composition database. Food categories were separated at posteriori in natural vs. were non-natural foods. Elevated BP was defined according to the 90th percentile cut-off values and was compared according to tertiles of fructose intake using univariable and multivariable mixed logistic regression models taking into account confounding factors: centre, sex, age and z-score-BMI, MVPA (Moderate to Vigorous Physical Activity) duration, tobacco consumption, salt intake and energy intake. RESULTS: Pure fructose from non-natural foods was only associated with elevated DBP (DBP above the 10th percentile in the highest consuming girls (OR = 2.27 (1.17-4.40); p = 0.015) after adjustment for cofounding factors. CONCLUSIONS: Consuming high quantities of non-natural foods was associated with elevated DBP in adolescent girls, which was in part due to high fructose levels in these foods categories. The consumption of natural foods containing fructose, such as whole fruits, does not impact blood pressure and should continue to remain a healthy dietary habit.

Measurement of Human Walking Movements by Using a Mobile Health App: Motion Sensor Data Analysis.

BACKGROUND: This study presents a new approach to measure and analyze the walking balance of humans by collecting motion sensor data in a smartphone. OBJECTIVE: We aimed to develop a mobile health (mHealth) app that can measure the walking movements of human individuals and analyze the differences in the walking movements of different individuals based on their health conditions. A smartphone's motion sensors were used to measure the walking movements and analyze the rotation matrix data by calculating the variation of each xyz rotation, which shows the variables in walking-related movement data over time. METHODS: Data were collected from 3 participants, that is, 2 healthy individuals (1 female and 1 male) and 1 male with back pain. The participant with back pain injured his back during strenuous exercise but he did not have any issues in walking. The participants wore the smartphone in the middle of their waistline (as the center of gravity) while walking. They were instructed to walk straight at their own pace in an indoor hallway of a building. The walked a distance of approximately 400 feet. They walked for 2-3 minutes in a straight line and then returned to the starting location. A rotation vector in the smartphone, calculated by the rotation matrix, was used to measure the pitch, roll, and yaw angles of the human body while walking. Each xyz-rotation vector datum was recalculated to find the variation in each participant's walking movement. RESULTS: The male participant with back pain showed a diminished level of walking balance with a wider range of xyz-axis variations in the rotations compared to those of the healthy participants. The standard deviation in the xyz-axis of the male participant with back pain was larger than that of the healthy male participant. Moreover, the participant with back pain had the widest combined range of right-to-left and forward-to-backward motions. The healthy male participant showed smaller standard deviation while walking than the male participant with back pain and the female healthy participant, indicating that the healthy male participant had a well-balanced walking movement. The walking movement of the female healthy participant showed symmetry in the left-to-right (x-axis) and up-to-down (y-axis) motions in the x-y variations of rotation vectors, indicating that she had lesser bias in gait than the others. CONCLUSIONS: This study shows that our mHealth app based on smartphone sensors and rotation vectors can measure the variations in the walking movements of different individuals. Further studies are needed to measure and compare walking movements by age, gender, as well as types of health problems or disease. This app can help in finding differences in gait in people with diseases that affect gait.

Upper Lip Tie: Anatomy, Effect on Breastfeeding, and Correlation With Ankyloglossia.

OBJECTIVES: There is debate among otolaryngologists and other practitioners about whether upper lip tie contributes to difficulty with breastfeeding and whether upper lip tie and ankyloglossia are linked. Our objectives were to evaluate the anatomy of the upper lip (maxillary) frenulum, to determine if the visual anatomy of the upper lip has an effect on breastfeeding, and to determine whether the occurrence of lip tie and tongue tie are correlated. METHODS: A prospective cohort study of 100 healthy newborns was examined between day of life 3-7. Surveys were completed by the mother at the time of the initial exam and 2 weeks later. The maxillary frenulum was graded based on the Stanford and Kotlow classifications by two independent reviewers. Inter-rater reliability and relationships between tongue tie, lip tie, and the infant breastfeeding assessment tool (IBFAT) were calculated. RESULTS: Inter-rater reliability showed fair agreement (κ = 0.302) using the Kotlow scale and better agreement using the Stanford classification (κ = 0.458). There was no correlation between the upper lip tie classification and breastfeeding success score. Lastly, there was a modest inverse correlation in the degree of tethering for the tongue and lip. CONCLUSIONS: There was no correlation between maxillary frenulum grade and comfort with breastfeeding, pain scores, or latch. There was also no relationship between tip to frenulum length (tongue tie) and visualized lip anatomy, suggesting that tongue tie and lip tie may not cluster together in infants. LEVEL OF EVIDENCE: 2 Laryngoscope, 131:E1701-E1706, 2021.

Heparin-mediated dimerization of follistatin.

Heparin and heparan sulfate (HS) are highly sulfated polysaccharides covalently bound to cell surface proteins, which directly interact with many extracellular proteins, including the transforming growth factor-ß (TGFß) family ligand antagonist, follistatin 288 (FS288). Follistatin neutralizes the TGFß ligands, myostatin and activin A, by forming a nearly irreversible non-signaling complex by surrounding the ligand and preventing interaction with TGFß receptors. The FS288-ligand complex has higher affinity than unbound FS288 for heparin/HS, which accelerates ligand internalization and lysosomal degradation; however, limited information is available for how FS288 interactions with heparin affect ligand binding. Using surface plasmon resonance (SPR) we show that preincubation of FS288 with heparin/HS significantly decreased the association kinetics for both myostatin and activin A with seemingly no effect on the dissociation rate. This observation is dependent on the heparin/HS chain length where small chain lengths less than degree of polymerization 10 (dp10) did not alter association rates but chain lengths >dp10 decreased association rates. In an attempt to understand the mechanism for this observation, we uncovered that heparin induced dimerization of follistatin. Consistent with our SPR results, we found that dimerization only occurs with heparin molecules >dp10. Small-angle X-ray scattering of the FS288 heparin complex supports that FS288 adopts a dimeric configuration that is similar to the FS288 dimer in the ligand-bound state. These results indicate that heparin mediates dimerization of FS288 in a chain-length-dependent manner that reduces the ligand association rate, but not the dissociation rate or antagonistic activity of FS288.

Age-Friendly Communities and Cultural Pluralism: Examining Saskatoon's Chinese-Canadian Social Enclave.

This article uses findings from qualitative interviews to examine the experiences of members of Saskatoon's Chinese-Canadian older-adult community in terms of their realities of aging and access to important geriatric resources. Promoting an understanding of both group experience and a broader conceptualization of age-friendly development, we argue that the notion and implications of a spatial ethnic enclave are replaced in the Saskatoon context by a social enclave. This network of social support is evident in Chinese-Canadian older adults' access to housing, recreation, transportation, and health services. The article concludes with lessons learned that would help enhance culturally pluralistic age-friendly development. This work underlines the significance of social capital development within more marginalized older-adult communities, both as a reaction to outside discrimination, and as a means of ensuring healthy and inclusive community aging.

Temperature dependency of predation: Increased killing rates and prey mass consumption by predators with warming.

Temperature dependency of consumer-resource interactions is fundamentally important for understanding and predicting the responses of food webs to climate change. Previous studies have shown temperature-driven shifts in herbivore consumption rates and resource preference, but these effects remain poorly understood for predatory arthropods. Here, we investigate how predator killing rates, prey mass consumption, and macronutrient intake respond to increased temperatures using a laboratory and a field reciprocal transplant experiment. Ectothermic predators, wolf spiders (Pardosa sp.), in the lab experiment, were exposed to increased temperatures and different prey macronutrient content (high lipid/low protein and low lipid/high protein) to assess changes in their killing rates and nutritional demands. Additionally, we investigate prey mass and lipid consumption by spiders under contrasting temperatures, along an elevation gradient. We used a field reciprocal transplant experiment between low (420 masl; 26°C) and high (2,100 masl; 15°C) elevations in the Ecuadorian Andes, using wild populations of two common orb-weaver spider species (Leucauge sp. and Cyclosa sp.) present along the elevation gradient. We found that killing rates of wolf spiders increased with warmer temperatures but were not significantly affected by prey macronutrient content, although spiders consumed significantly more lipids from lipid-rich prey. The field reciprocal transplant experiment showed no consistent predator responses to changes in temperature along the elevational gradient. Transplanting Cyclosa sp. spiders to low- or high-elevation sites did not affect their prey mass or lipid consumption rate, whereas Leucauge sp. individuals increased prey mass consumption when transplanted from the high to the low warm elevation. Our findings show that increases in temperature intensify predator killing rates, prey consumption, and lipid intake, but the responses to temperature vary between species, which may be a result of species-specific differences in their hunting behavior and sensitivity to temperature.