Fetal heart rate responses in chronic hypoxaemia with superimposed repeated hypoxaemia consistent with early labour: a controlled study in fetal sheep.

OBJECTIVE: Deceleration area (DA) and capacity (DC) of the fetal heart rate can help predict risk of intrapartum fetal compromise. However, their predictive value in higher risk pregnancies is unclear. We investigated whether they can predict the onset of hypotension during brief hypoxaemia repeated at a rate consistent with early labour in fetal sheep with pre-existing hypoxaemia. DESIGN: Prospective, controlled study. SETTING: Laboratory. SAMPLE: Chronically instrumented, unanaesthetised near-term fetal sheep. METHODS: One-minute complete umbilical cord occlusions (UCOs) were performed every 5 minutes in fetal sheep with baseline pa O2 <17 mmHg (hypoxaemic, n = 8) and >17 mmHg (normoxic, n = 11) for 4 hours or until arterial pressure fell <20 mmHg. MAIN OUTCOME MEASURES: DA, DC and arterial pressure. RESULTS: Normoxic fetuses showed effective cardiovascular adaptation without hypotension and mild acidaemia (lowest arterial pressure 40.7 ± 2.8 mmHg, pH 7.35 ± 0.03). Hypoxaemic fetuses developed hypotension (lowest arterial pressure 20.8 ± 1.9 mmHg, P < 0.001) and acidaemia (final pH 7.07 ± 0.05). In hypoxaemic fetuses, decelerations showed faster falls in FHR over the first 40 seconds of UCOs but the final deceleration depth was not different to normoxic fetuses. DC was modestly higher in hypoxaemic fetuses during the penultimate (P = 0.04) and final (P = 0.012) 20 minutes of UCOs. DA was not different between groups. CONCLUSION: Chronically hypoxaemic fetuses had early onset of cardiovascular compromise during labour-like brief repeated UCOs. DA was unable to identify developing hypotension in this setting, while DC only showed modest differences between groups. These findings highlight that DA and DC thresholds need to be adjusted for antenatal risk factors, potentially limiting their clinical utility.

The healthy equine uterus harbors a distinct core microbiome plus a rich and diverse microbiome that varies with geographical location.

The goal of this study was to understand the composition and existence of the resident uterine microbiome in healthy mares and to establish the presence of a core microbiome for the healthy equine uterus. We analyzed the microbiomes of 35 healthy mares that are long-time residents of three farms in Oklahoma, Louisiana, and Australia as well as that of 19 mares purchased from scattered owners in the Southern Mid-Western states of the United States. Over 6 million paired-end reads of the V4 region of the 16S rRNA gene were obtained resulting in 19,542 unique Amplicon Sequence Variants (ASVs). ASVs were assigned to 17 known phyla and 213 known genera. Most abundant genera across all animals were Pseudomonas (27%) followed by Lonsdalea (8%), Lactobacillus (7.5%), Escherichia/Shigella (4.5%), and Prevotella (3%). Oklahoma and Louisiana samples were dominated by Pseudomonas (75%). Lonsdalea (28%) was the most abundant genus in the Australian samples but was not found in any other region. Microbial diversity, richness, and evenness of the equine uterine microbiome is largely dependent on the geographical location of the animal. However, we observed a core uterine microbiome consisting of Lactobacillus, Escherichia/Shigella, Streptococcus, Blautia, Staphylococcus, Klebsiella, Acinetobacter, and Peptoanaerobacter.

Scoping Review of Oral Health-Related Birth Cohort Studies: Toward a Global Consortium.

The multidisciplinary nature and long duration of birth cohort studies allow investigation of the relationship between general and oral health and indicate the most appropriate stages in life to intervene. To date, the worldwide distribution of oral health-related birth cohort studies (OHRBCSs) has not been mapped, and a synthesis of information on methodological characteristics and outcomes is not available. We mapped published literature on OHRBCSs, describing their oral health-related data and methodological aspects. A 3-step search strategy was adopted to identify published studies using PubMed, Embase, Web of Science, and OVID databases. Studies with baseline data collection during pregnancy or within the first year of life or linked future oral health data to exposures during either of these 2 life stages were included. Studies examining only mothers' oral health and specific populations were excluded. In total, 1,721 articles were suitable for initial screening of titles and abstracts, and 528 articles were included in the review, identifying 120 unique OHRBCSs from 34 countries in all continents. The review comprised literature from the mid-1940s to the 21st century. Fifty-four percent of the OHRBCSs started from 2000 onward, and 75% of the cohorts were from high-income and only 2 from low-income countries. The participation rate between the baseline and the last oral health follow-up varied between 7% and 93%. Ten cohorts that included interventions were mostly from 2000 and with fewer than 1,000 participants. Seven data-linkage cohorts focused mostly on upstream characteristics and biological aspects. The most frequent clinical assessment was dental caries, widely presented as decayed, missing, and filled teeth (DMFT/dmft). Periodontal conditions were primarily applied as isolated outcomes or as part of a classification system. Socioeconomic classification, ethnicity, and country- or language-specific assessment tools varied across countries. Harmonizing definitions will allow combining data from different studies, adding considerable strength to data analyses; this will be facilitated by forming a global consortium.

NEIL1 and NEIL2 DNA glycosylases modulate anxiety and learning in a cooperative manner in mice.

Oxidative DNA damage in the brain has been implicated in neurodegeneration and cognitive decline. DNA glycosylases initiate base excision repair (BER), the main pathway for oxidative DNA base lesion repair. NEIL1 and NEIL3 DNA glycosylases affect cognition in mice, while the role of NEIL2 remains unclear. Here, we investigate the impact of NEIL2 and its potential overlap with NEIL1 on behavior in knockout mouse models. Neil1-/-Neil2-/- mice display hyperactivity, reduced anxiety and improved learning. Hippocampal oxidative DNA base lesion levels are comparable between genotypes and no mutator phenotype is found. Thus, impaired canonical repair is not likely to explain the altered behavior. Electrophysiology suggests reduced axonal activation in the hippocampal CA1 region in Neil1-/-Neil2-/- mice and lack of NEIL1 and NEIL2 causes dysregulation of genes in CA1 relevant for synaptic function. We postulate a cooperative function of NEIL1 and NEIL2 in genome regulation, beyond canonical BER, modulating behavior in mice.

A survey of producer practices and reproductive performance of containment and supplementary fed ewes.

Containment feeding, where ewes are fed complete rations, is used to maintain flock numbers in periods of inadequate pasture supply. Producer practices influence both the reproductive performance of ewes and the risk of health challenges. The aim of this study was to evaluate the reproductive, feeding and health management practices of producers using containment or supplementary feeding, and quantify any associations between practice and reproductive performance. An online survey of Australian producers was conducted in 2020. The number of responses (n = 43) allowed benchmarking but was insufficient to determine correlations between practice and performance. The reported pregnancy rate of adult Merino ewes was variable between respondents (78%-95%; n = 11), and lambs marked per ewe joined ranged from 60% to 110% (n = 9). In non-Merino flocks, lambs marked ranged from 82% to 161% (n = 4). Most respondents (9/11) fed cereal grain with hay or straw, either daily or two or three times a week. However, some respondents fed grain only or roughage only, such that the percentage of roughage in diets ranged from 0% to 100%. Ewes were most frequently separated into age groups for feeding, and shy feeders were only removed by 25% of respondents. Although generally the reported reproductive rate was high, wide variation indicates potential for improvement. Best practice management for containment remains unclear and requires further research given the diverse practices used. Veterinary practitioners should be aware that some of the practices used may contribute to reduced productivity or health issues in ewes.

Deceleration area and capacity during labour-like umbilical cord occlusions identify evolving hypotension: a controlled study in fetal sheep.

OBJECTIVE: Cardiotocography is widely used to assess fetal well-being during labour. The positive predictive value of current clinical algorithms to identify hypoxia-ischaemia is poor. In experimental studies, fetal hypotension is the strongest predictor of hypoxic-ischaemic injury. Cohort studies suggest that deceleration area and deceleration capacity of the fetal heart rate trace correlate with fetal acidaemia, but it is not known whether they are indices of fetal arterial hypotension. DESIGN: Prospective, controlled study. SETTING: Laboratory. SAMPLE: Near-term fetal sheep. METHODS: One minute of complete umbilical cord occlusions (UCOs) every 5 minutes (1:5 min, n = 6) or every 2.5 minutes (1:2.5 min, n = 12) for 4 hours or until fetal mean arterial blood pressure fell <20 mmHg. MAIN OUTCOME MEASURES: Deceleration area and capacity during the UCO series were related to evolving hypotension. RESULTS: The 1:5 min group developed only mild metabolic acidaemia, without hypotension. By contrast, 10/12 fetuses in the 1:2.5-min group progressively developed severe metabolic acidaemia and hypotension, reaching 16.8 ± 0.9 mmHg after 71.2 ± 6.7 UCOs. Deceleration area and capacity remained unchanged throughout the UCO series in the 1:5-min group, but progressively increased in the 1:2.5-min group. The severity of hypotension was closely correlated with both deceleration area (P < 0.001, R2  = 0.66, n = 18) and capacity (P < 0.001, R2  = 0.67, n = 18). Deceleration area and capacity predicted development of hypotension at a median of 103 and 123 minutes before the final occlusion, respectively. CONCLUSIONS: Both deceleration area and capacity were strongly associated with developing fetal hypotension, supporting their potential to improve identification of fetuses at risk of hypotension leading to hypoxic-ischaemic injury during labour. TWEETABLE ABSTRACT: Deceleration area and capacity of fetal heart rate identify developing hypotension during labour-like hypoxia.

Hydroureteronephrosis and fetal mummification secondary to uterine torsion in a Merino ewe.

A 6 year old pluriparous Merino ewe was presented for investigation of a large intra-abdominal mass. Post-mortem examination revealed a 360° clockwise uterine torsion was present with a mummifying fetus. The torsion involved the left ureter resulting in a severe hydroureteronephrosis. Uterine torsion is uncommon in the ewe, occurring in less than 0.1% of pregnancies in one report (Mahmoud et al. Livest Res Rural Dev 2018;30), but cases are likely to be undiagnosed, particularly under the extensive management conditions typical of Australia. The chronicity of the condition in this ewe would support this statement. To the authors' knowledge this is the first reported case of hydroureteronephrosis secondary to uterine torsion in any species.

Oral Health Birth Cohort Studies: Achievements, Challenges, and Potential.

Birth cohorts are those among observational studies that provide understanding of the natural history and causality of diseases since early in life. Discussions during an International Association for Dental Research symposium in London, United Kingdom, in 2018, followed by a workshop in Bangkok, Thailand, in 2019, concluded that there are few birth cohort studies that consider oral health and that a broader discussion on similarities and differences among those studies would be valuable. This article aims to 1) bring together available long-term data of oral health birth cohort studies from the low, middle, and high-income countries worldwide and 2) describe similarities and differences among these studies. This work comprises 15 studies from all 5 continents. The most studied dental conditions and exposures are identified; findings are summarized; and methodological differences and similarities among studies are presented. Methodological strengths and weaknesses are also highlighted. Findings are summarized in 1) the negative impact of detrimental socioeconomic status on oral health changes over time, 2) the role of unfavorable patterns of dental visiting on oral health, 3) associations between general and oral health, 4) nutritional and dietary effects on oral health, and 5) intergenerational influences on oral health. Dental caries and dental visiting patterns have been recorded in all studies. Sources of fluoride exposure have been documented in most of the more recent studies. Despite some methodological differences in the way that the exposures and outcomes were measured, some findings are consistent. Predictive models have been used with caries risk tools, periodontitis occurrence, and permanent dentition orthodontic treatment need. The next steps of the group's work are as follows: 1) establishing a consortium of oral health birth cohort studies, 2) conducting a scoping review, 3) exploring opportunities for pooled data analyses to answer pressing research questions, and 4) promoting and enabling the development of the next generation of oral health researchers.

OXR1A, a Coactivator of PRMT5 Regulating Histone Arginine Methylation.

Oxidation resistance gene 1 (OXR1) protects cells against oxidative stress. We find that male mice with brain-specific isoform A knockout (Oxr1A-/-) develop fatty liver. RNA sequencing of male Oxr1A-/- liver indicates decreased growth hormone (GH) signaling, which is known to affect liver metabolism. Indeed, Gh expression is reduced in male mice Oxr1A-/- pituitary gland and in rat Oxr1A-/- pituitary adenoma cell-line GH3. Oxr1A-/- male mice show reduced fasting-blood GH levels. Pull-down and proximity ligation assays reveal that OXR1A is associated with arginine methyl transferase PRMT5. OXR1A-depleted GH3 cells show reduced symmetrical dimethylation of histone H3 arginine 2 (H3R2me2s), a product of PRMT5 catalyzed methylation, and chromatin immunoprecipitation (ChIP) of H3R2me2s shows reduced Gh promoter enrichment. Finally, we demonstrate with purified proteins that OXR1A stimulates PRMT5/MEP50-catalyzed H3R2me2s. Our data suggest that OXR1A is a coactivator of PRMT5, regulating histone arginine methylation and thereby GH production within the pituitary gland.

An interdisciplinary and catchment approach to enhancing urban flood resilience: a Melbourne case.

This paper presents a novel interdisciplinary and catchment-based approach for exploring urban flood resilience. Our research identified and developed a diverse set of adaptation measures for Elwood, a suburb in Melbourne, Australia, that is vulnerable to pluvial and coastal flooding. We drew on methods from social science, urban design and environmental engineering to gain integrated insights into the opportunities for Elwood to increase its flood resilience and urban liveability. Results showed that an appropriate balance of social, infrastructural and urban design responses would be required to retreat from, accommodate and protect against flood risk. These would also deliver broader benefits such as securing water supplies through harvested stormwater and mitigating extreme heat through greener landscapes. Our interdisciplinary approach demonstrated the value of (i) engaging with the community to understand their concerns, aspirations and adaptation ideas, (ii) exploring design measures that densify and use urban forms in ways that implement adaptation measures while responding to local context, (iii) adopting modelling techniques to test the performance, robustness and economic viability of possible adaptation solutions, and (iv) innovating governance arrangements and principles needed to improve flood resilience in the Elster Creek catchment. Our research also provided valuable insight on how to operationalize interdisciplinary work in practice, highlighting the importance of sharing an impact agenda, taking a place-based approach, developing a common conceptual framework, and fostering a constructive team culture. This article is part of the theme issue 'Urban flood resilience'.

Fluoride Revolution and Dental Caries: Evolution of Policies for Global Use.

Epidemiological studies over 70 y ago provided the basis for the use of fluoride in caries prevention. They revealed the clear relation between water fluoride concentration, and therefore fluoride exposure, and prevalence and severity of dental fluorosis and dental caries. After successful trials, programs for water fluoridation were introduced, and industry developed effective fluoride-containing toothpastes and other fluoride vehicles. Reductions in caries experience were recorded in many countries, attributable to the widespread use of fluoride. This is a considerable success story; oral health for many was radically improved. While previously, water had been the only significant source of fluoride, now there are many, and this led to an increase in the occurrence of dental fluorosis. Risks identified for dental fluorosis were ingestion of fluoride-containing toothpaste, water fluoridation, fluoride tablets (which were sometimes ingested in areas with water fluoridation), and infant formula feeds. Policies were introduced to reduce excessive fluoride exposure during the period of tooth development, and these were successful in reducing dental fluorosis without compromising caries prevention. There is now a much better understanding of the public perception of dental fluorosis, with mild fluorosis being of no aesthetic concern. The advantages of water fluoridation are that it provides substantial lifelong caries prevention, is economic, and reduces health inequalities: it reaches a substantial number of people worldwide. Fluoride-containing toothpastes are by far the most important way of delivering the beneficial effect of fluoride worldwide. The preventive effects of conjoint exposure (e.g., use of fluoride toothpaste in a fluoridated area) are additive. The World Health Organization has informed member states of the benefits of the appropriate use of fluoride. Many countries have policies to maximize the benefits of fluoride, but many have yet to do so.

Differential effects of slow rewarming after cerebral hypothermia on white matter recovery after global cerebral ischemia in near-term fetal sheep.

It is widely believed that rewarming slowly after therapeutic hypothermia for hypoxic-ischemic (HI) encephalopathy can improve outcomes, but its impact on white matter injury after HI is unclear. Fetal sheep (0.85 gestation) received 30 min ischemia-normothermia (n = 8), or hypothermia from 3-48 h with rapid spontaneous rewarming over 1 h (ischemia-48 h hypothermia, n = 8), or 48 h with slow rewarming over 24 h (ischemia-slow rewarming, n = 7) or 72 h with rapid rewarming (ischemia-72 h hypothermia, n = 8). Ischemia was associated with loss of total and mature oligodendrocytes and reduced area fraction of myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase; immature/mature oligodendrocytes) and increased microglia and astrocytes. Total numbers of oligodendrocytes were increased by all hypothermia protocols but only ischemia-72 h hypothermia attenuated loss of mature oligodendrocytes. All hypothermia protocols similarly increased the area fraction of MBP, whereas there was only an intermediate effect on the area fraction of CNPase. Microglia were suppressed by all hypothermia protocols, with the greatest reduction after ischemia-72 h hypothermia, and an intermediate effect after ischemia-slow rewarming. By contrast, induction of astrocytes was significantly reduced only after ischemia-slow rewarming. In conclusion, slow rewarming after hypothermia did not improve oligodendrocyte survival or myelination or suppression of microgliosis compared to fast rewarming, but modestly reduced astrocytosis.

Identification and characterisation of anti - Pseudomonas aeruginosa proteins in mucus of the brown garden snail, Cornu aspersum.

Background: Novel antimicrobial treatments are urgently needed. Previous work has shown that the mucus of the brown garden snail (Cornu aspersum) has antimicrobial properties, in particular against type culture collection strains of Pseudomonas aeruginosa. We hypothesised that it would also be effective against clinical isolates of the bacterium and that investigation of fractions of the mucus would identify one or more proteins with anti-pseudomonal properties, which could be further characterised. Materials and methods: Mucus was extracted from snails collected from the wild. Antimicrobial activity against laboratory and clinical isolates of Ps. aeruginosa was determined in disc diffusion assays. Mucus was purified using size exclusion chromatography and fractions containing anti-pseudomonal activity identified. Mass spectroscopy and high performance liquid chromatography analysis of these fractions yielded partial peptide sequences. These were used to interrogate an RNA transcriptome generated from whole snails. Results: Mucus from C. aspersum inhibited growth of type collection strains and clinical isolates of Ps. aeruginosa. Four novel C. aspersum proteins were identified; at least three are likely to have antimicrobial properties. The most interesting is a 37.4 kDa protein whilst smaller proteins, one 17.5 kDa and one 18.6 kDa also appear to have activity against Ps. aeruginosa. Conclusions: The study has identified novel proteins with antimicrobial properties which could be used to develop treatments for use in human medicine.

Fluoridated Water Modifies the Effect of Breastfeeding on Dental Caries.

Breastfeeding is important for health and development. Yet, the interaction between breastfeeding duration and usage of fluoridated water on caries experience has not been investigated. This study examined exposure to fluoridation as an effect modifier of the association between breastfeeding duration and caries. The 2012 to 2014 national population-based study of Australian children involved parental questionnaires and oral epidemiological assessment. Children were grouped by parent-reported breastfeeding duration into minimal (none or <1 mo), breastfed for 1 to <6 mo, breastfed for 6 to 24 mo, and sustained (>24 mo). Residential history and main water source used for the first 2 y of life were collected to group children into exposed (WF) and nonexposed (NF) to fluoridation. Socioeconomic status, infant formula feeding, and sugar-sweetened beverage (SSB) consumption data were collected. The prevalence and severity of caries in children aged 5 to 6 y were primary outcomes. Multivariable regression models with robust error estimation were generated to compute prevalence ratios (PRs) and mean ratios (MRs) for 3 breastfeeding groups against the reference (breastfed for 6-24 mo). Of the 5- to 6-y-old children, 2,721 were in the WF and 1,737 were in the NF groups. The groups had comparable distributions of socioeconomic factors, infant formula feeding, and SSB consumption. There were U-shape distributions of caries experience among breastfeeding groups, being more pronounced among NF children. Among NF children, the minimal and sustained breastfeeding groups had significantly higher PR (1.4 [1.1-1.9] and 1.8 [1.4-2.4]) and MR (2.1 [1.4-3.3] and 2.4 [1.4-4.1]) than the reference group. However, among the WF children, this association between breastfeeding duration and caries attenuated after adjustment for other factors. The study contributes evidence of a nonlinear (U-shape) association between breastfeeding duration and dental caries. Early life exposure to fluoridated drinking water attenuated the potential cariogenic effect of both lack of and sustained breastfeeding.

Breastfeeding and Oral Health: Evidence and Methodological Challenges.

Breastfeeding is a powerful health-promoting behavior. A 2016 Lancet global collaboration to review the health implications of breastfeeding was among the first to consider oral health outcomes. While a role was suggested for breastfeeding in preventing malocclusion, caries was the only included disease condition unfavorably associated with breastfeeding. The present critical review examines the evidence connecting breastfeeding practices to these outcomes and discusses the methodological challenges inherent in reaching causal conclusions. Published systematic reviews show some evidence of a protective effect of breastfeeding against primary dentition malocclusion but no supportive evidence for mixed dentition and permanent dentition malocclusions. Regarding caries, well-conducted studies report a benefit with breastfeeding up to 12 mo but a positive association between caries and breastfeeding of longer duration, at times that vary between 12 and 24 mo, as well as nocturnal feeding. Future studies would be methodologically stronger if focused on specific malocclusion traits that are plausibly associated with sucking movements rather than using general malocclusion indices. Studies should use detailed and consistent terminology for breastfeeding definition, including frequency, intensity, and timing. Analytical studies should be carried out to distinguish between confounders (e.g., prematurity) and mediators (e.g., use of pacifier). Regarding a link to caries, standard terminology for exposures (e.g., nocturnal feeding) is recommended. Statistical analyses must account for known confounding factors (e.g., socioeconomic conditions) but avoid inappropriate adjustment for variables on a causal path between exposure and outcome or for variables not associated with breastfeeding (e.g., tooth brushing), as can be guided using tools such as direct acyclic graphs. For dental practice, the potential caries risk of long-duration breastfeeding should be part of individual patient counseling that incorporates patient values and circumstances. Given the unquestioned overall health benefits of breastfeeding, the dental community should support World Health Organization guidelines that encourage and promote breastfeeding.