Gene-environment interactions within a precision environmental health framework.

Understanding the complex interplay of genetic and environmental factors in disease etiology and the role of gene-environment interactions (GEIs) across human development stages is important. We review the state of GEI research, including challenges in measuring environmental factors and advantages of GEI analysis in understanding disease mechanisms. We discuss the evolution of GEI studies from candidate gene-environment studies to genome-wide interaction studies (GWISs) and the role of multi-omics in mediating GEI effects. We review advancements in GEI analysis methods and the importance of large-scale datasets. We also address the translation of GEI findings into precision environmental health (PEH), showcasing real-world applications in healthcare and disease prevention. Additionally, we highlight societal considerations in GEI research, including environmental justice, the return of results to participants, and data privacy. Overall, we underscore the significance of GEI for disease prediction and prevention and advocate for integrating the exposome into PEH omics studies.

Geographic source of bats killed at wind-energy facilities in the eastern United States.

Bats subject to high rates of fatalities at wind-energy facilities are of high conservation concern due to the long-term, cumulative effects they have, but the impact on broader bat populations can be difficult to assess. One reason is the poor understanding of the geographic source of individual fatalities and whether they constitute migrants or more local individuals. Here, we used stable hydrogen isotopes, trace elements and species distribution models to determine the most likely summer geographic origins of three different bat species (Lasiurus borealis, L. cinereus, and Lasionycteris noctivagans) killed at wind-energy facilities in Ohio and Maryland in the eastern United States. In Ohio, 41.6%, 21.3%, 2.2% of all individuals of L. borealis, L. cinereus, and L. noctivagans, respectively, had evidence of movement. In contrast, in Maryland 77.3%, 37.1%, and 27.3% of these same species were classified as migrants. Our results suggest bats killed at a given wind facility are likely derived from migratory as well as resident populations. Finally, there is variation in the proportion of migrants killed between seasons for some species and evidence of philopatry to summer roosts. Overall, these results indicate that the impact of wind-energy facilities on bat populations occurs across a large geographic extent, with the proportion of migrants impacted likely to vary across species and sites. Similar studies should be conducted across a broader geographic scale to understand the impacts on bat populations from wind-energy facilities.

Analysis of primary care electronic health record data of people living with hepatitis B virus: infection and hepatocellular carcinoma risk associated with socio-economic deprivation.

OBJECTIVES: We set out to characterise chronic hepatitis B (CHB) in the primary care population in England and investigate risk factors for progression to hepatocellular carcinoma (HCC). STUDY DESIGN: Retrospective cohort study. METHODS: We identified 8039 individuals with CHB in individuals aged ≥18 years between 1999 and 2019 in the English primary care database QResearch. HCC risk factors were investigated using Cox proportional hazards modelling. RESULTS: Most of those with a record of CHB were males (60%) of non-White ethnicity (>70%), and a high proportion were in the most deprived Townsend deprivation quintile (44%). Among 7029 individuals with longitudinal data, 161 HCC cases occurred. Increased HCC hazards were significantly associated with male sex (adjusted hazards ratio [aHR] 3.17, 95% confidence interval [95% CI] 1.92-5.23), in the fifth deprivation quintile as compared to the third quintile (aHR 1.69, 95% CI 1.01-2.84), with older age (for age groups 56-65 and ≥66 years, compared to 26-35 years, aHRs 2.82 [95% CI 1.45-5.46] and 3.76 [95% CI 1.79-7.9], respectively), Caribbean ethnicity (aHR 3.32, 95% CI 1.43-7.71, compared to White ethnicity), ascites (aHR 3.15, 95% CI 1.30-7.67), cirrhosis (aHR 6.55, 95% CI 4.57-9.38) and peptic ulcer disease (aHR 2.26, 95% CI 1.45-3.51). CONCLUSIONS: Targeting interventions and HCC surveillance at vulnerable groups is essential to improve CHB outcomes and to support progress towards international goals for the elimination of hepatitis infection as a public health threat.

Pork muscle profiling: pH and instrumental color of the longissimus thoracis is not representative of pH and instrumental color of shoulder and ham muscles.

From a population of 351 pork carcasses, 3.0-cm thick chops from the 10th rib location of the longissimus thoracis, faced surfaces of the triceps brachii and serratus ventralis muscles from the boneless shoulder, and faced surfaces of the biceps femoris, semitendinosus, semimembranosus, adductor, rectus femoris, and vastus lateralis muscles from the boneless ham were evaluated for pH and instrumental color (Minolta CR-400). Evaluations were conducted for at least three different locations on each of the muscle samples and averaged before data analysis occurred. The longissimus thoracis had the lowest pH and the lightest and least red color compared with the other eight muscles evaluated in this study (mean differences ranged from 0.98 to 8.70 for L*, 3.98 to 12.56 for a*, and 0.026 to 0.409 for pH). Furthermore, regression analysis suggested that pH and color values for the longissimus thoracis were not adequate predictors for pH and color values obtained from other muscles and therefore consideration should be given to the individual muscles that are of interest.

Whole-genome sequencing to investigate transmission of SARS-CoV-2 in the acute healthcare setting: a systematic review.

BACKGROUND: Whole-genome sequencing (WGS) has been used widely to elucidate transmission of SARS-CoV-2 in acute healthcare settings, and to guide infection, prevention, and control (IPC) responses. AIM: To systematically appraise available literature, published between January 1st, 2020 and June 30th, 2022, describing the implementation of WGS in acute healthcare settings to characterize nosocomial SARS-CoV-2 transmission. METHODS: Searches of the PubMed, Embase, Ovid MEDLINE, EBSCO MEDLINE, and Cochrane Library databases identified studies in English reporting the use of WGS to investigate SARS-CoV-2 transmission in acute healthcare environments. Publications involved data collected up to December 31st, 2021, and findings were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. FINDINGS: In all, 3088 non-duplicate records were retrieved; 97 met inclusion criteria, involving 62 outbreak analyses and 35 genomic surveillance studies. No publications from low-income countries were identified. In 87/97 (90%), WGS supported hypotheses for nosocomial transmission, while in 46 out of 97 (47%) suspected transmission events were excluded. An IPC intervention was attributed to the use of WGS in 18 out of 97 (18%); however, only three (3%) studies reported turnaround times ≤7 days facilitating near real-time IPC action, and none reported an impact on the incidence of nosocomial COVID-19 attributable to WGS. CONCLUSION: WGS can elucidate transmission of SARS-CoV-2 in acute healthcare settings to enhance epidemiological investigations. However, evidence was not identified to support sequencing as an intervention to reduce the incidence of SARS-CoV-2 in hospital or to alter the trajectory of active outbreaks.

"Oh! How Modern! And... Are You Ok with That?": Consensually Non-Monogamous People's Experiences When Accessing Sexual Health Care.

The current research explored consensually non-monogamous peoples' experiences accessing sexual healthcare. Using a mixed method approach, a sample of 67 consensually non-monogamous individuals (48% Polyamorous; 42% Relationship Anarchy/Solo polyamory; 6% Swingers; 4% Uncategorized) reported having significantly lower rates of trust in healthcare professionals compared to standardized scores. Sixty-three percent of participants reported disclosing their relationship status to a clinician when accessing sexual health services, whereas 37% sometimes or never disclosed. Qualitative responses identified that some participants reported a willingness to be open about their relationships, but many chose to "pass" as monogamous to both simplify and streamline their interactions as well as to avoid potential stigma. Participants reported a wide range of experiences with clinicians from those who were accepting and professional, to some who displayed prejudice and withheld treatment. This research outlines some of the experiences and challenges presented to consensual non-monogamists when accessing sexual healthcare as well as providing suggestions for clinicians to help remove some of the barriers to appropriate patient care.

Microsecond Isomer at the N=20 Island of Shape Inversion Observed at FRIB.

Excited-state spectroscopy from the first experiment at the Facility for Rare Isotope Beams (FRIB) is reported. A 24(2)-µs isomer was observed with the FRIB Decay Station initiator (FDSi) through a cascade of 224- and 401-keV γ rays in coincidence with ^{32}Na nuclei. This is the only known microsecond isomer (1 µs≤T_{1/2}<1 ms) in the region. This nucleus is at the heart of the N=20 island of shape inversion and is at the crossroads of the spherical shell-model, deformed shell-model, and ab initio theories. It can be represented as the coupling of a proton hole and neutron particle to ^{32}Mg, ^{32}Mg+π^{-1}+ν^{+1}. This odd-odd coupling and isomer formation provides a sensitive measure of the underlying shape degrees of freedom of ^{32}Mg, where the onset of spherical-to-deformed shape inversion begins with a low-lying deformed 2^{+} state at 885 keV and a low-lying shape-coexisting 0_{2}^{+} state at 1058 keV. We suggest two possible explanations for the 625-keV isomer in ^{32}Na: a 6^{-} spherical shape isomer that decays by E2 or a 0^{+} deformed spin isomer that decays by M2. The present results and calculations are most consistent with the latter, indicating that the low-lying states are dominated by deformation.

Crossing N=28 Toward the Neutron Drip Line: First Measurement of Half-Lives at FRIB.

New half-lives for exotic isotopes approaching the neutron drip-line in the vicinity of N∼28 for Z=12-15 were measured at the Facility for Rare Isotope Beams (FRIB) with the FRIB decay station initiator. The first experimental results are compared to the latest quasiparticle random phase approximation and shell-model calculations. Overall, the measured half-lives are consistent with the available theoretical descriptions and suggest a well-developed region of deformation below ^{48}Ca in the N=28 isotones. The erosion of the Z=14 subshell closure in Si is experimentally confirmed at N=28, and a reduction in the ^{38}Mg half-life is observed as compared with its isotopic neighbors, which does not seem to be predicted well based on the decay energy and deformation trends. This highlights the need for both additional data in this very exotic region, and for more advanced theoretical efforts.

Guillain-Barré Syndrome and Unilateral Optic Neuritis Following Vaccination for COVID-19: A Case Report and Literature Review.

A 71-year-old woman presented 2 weeks after vaccination with the first dose of Vaxzevria (AstraZeneca, Oxford) for COVID-19 with a left lower motor neuron facial nerve palsy, which progressed to bilateral involvement. This was accompanied by bilateral proximal leg weakness. She was diagnosed with the 'facial diplegia with paraesthesia' variant of Guillain-Barré syndrome. Seven weeks post vaccination she developed painless loss of vision in the right eye. The visual acuity in that eye was light perception only with a right relative afferent pupillary defect and right optic disc swelling. A diagnosis of optic neuritis was made and she received pulsed intravenous methylprednisolone for 3 days, followed by oral prednisolone. The optic neuritis recurred following initial cessation of steroids requiring an extended course of steroids. Despite this, she made a good visual recovery to 6/6 in the affected eye. We present this case and a review of the literature surrounding vaccination and the development of these conditions.

Diclidophora merlangi (Kuhn, 1829) Krøyer, 1838 (Monogenea: Diclidophoridae) as an indicator of hydrocarbon pollution in the North Sea.

This study presents the results of analyses of data on infections of 2646 whiting Merlangius merlangus with the monogenean Diclidophora merlangi. All fish were caught in the North Sea and off the north coast of Scotland in 1990, 1993 and 1995. The aims were to analyse these data in relation to the locations of whiting sampling stations and oil installations active at that time, and to evaluate the results in terms of D. merlangi as an indicator of hydrocarbon pollution. Mean abundance of D. merlangi increased significantly with increasing proximity to the nearest oil field, with an accelerated rate of increase within approximately 2 km of the oil field. Age of oil field and whiting length showed no significant effect on parasite abundance, but there was a small difference between years. The results support those of previous studies in demonstrating the value of monogeneans as indicators of hydrocarbon pollution.

Cervical cancer screening utilization, and associated factors, in Nepal: a systematic review and meta-analysis.

OBJECTIVE: To systematically appraise the existing published literature on cervical cancer screening utilization, and associated barriers and facilitators, in Nepal. STUDY DESIGN: Systematic literature review and meta-analysis. METHODS: PubMed/MEDLINE, CINAHL, Scopus, Embase, and, Google Scholar were systematically searched using Preferred Reporting Items for Systematic Review and Meta-Analysis guideline. All quantitative and qualitative studies reporting cervical cancer screening (using the Pap smear test or visual inspection with acetic acid or human papillomavirus test) utilization, barriers, and facilitators for screening were identified. A meta-analysis was performed to estimate Nepal's pooled cervical cancer screening utilization proportion. RESULTS: The search yielded 97 records, of which 17 studies were included. Fifteen studies were quantitative and two were qualitative. Of the 17 studies, six were hospital-based and six were community-based. The pooled cervical cancer screening utilization proportion (using Pap smear test) among Nepalese women was 17% from the studies in the hospital settings, and 16% in the community. Six studies reported barriers to cervical cancer screening, of which four reported embarrassments related to the gynecological examination and a low level of knowledge on cervical cancer. Three (of four) studies reported health personnel, and two studies reported screening services-related facilitators for cervical cancer screening. CONCLUSION: Our review reported that cervical cancer screening utilization (16%) is more than four times lower than the national target (70%) in Nepal. Multiple barriers such as low levels of knowledge and embarrassment are associated with cervical cancer screening utilization. Health personnel's gender, counseling, and privacy of screening services were commonly reported facilitators. These findings could help to inform future research, and policy efforts to increase cervical cancer screening utilization in Nepal.

Multi-qubit entanglement and algorithms on a neutral-atom quantum computer.

Gate-model quantum computers promise to solve currently intractable computational problems if they can be operated at scale with long coherence times and high-fidelity logic. Neutral-atom hyperfine qubits provide inherent scalability owing to their identical characteristics, long coherence times and ability to be trapped in dense, multidimensional arrays1. Combined with the strong entangling interactions provided by Rydberg states2-4, all the necessary characteristics for quantum computation are available. Here we demonstrate several quantum algorithms on a programmable gate-model neutral-atom quantum computer in an architecture based on individual addressing of single atoms with tightly focused optical beams scanned across a two-dimensional array of qubits. Preparation of entangled Greenberger-Horne-Zeilinger (GHZ) states5 with up to six qubits, quantum phase estimation for a chemistry problem6 and the quantum approximate optimization algorithm (QAOA)7 for the maximum cut (MaxCut) graph problem are demonstrated. These results highlight the emergent capability of neutral-atom qubit arrays for universal, programmable quantum computation, as well as preparation of non-classical states of use for quantum-enhanced sensing.

Pedigree-based and phylogenetic methods support surprising patterns of mutation rate and spectrum in the gray mouse lemur.

Mutations are the raw material on which evolution acts, and knowledge of their frequency and genomic distribution is crucial for understanding how evolution operates at both long and short timescales. At present, the rate and spectrum of de novo mutations have been directly characterized in relatively few lineages. Our study provides the first direct mutation-rate estimate for a strepsirrhine (i.e., the lemurs and lorises), which comprises nearly half of the primate clade. Using high-coverage linked-read sequencing for a focal quartet of gray mouse lemurs (Microcebus murinus), we estimated the mutation rate to be among the highest calculated for a mammal at 1.52 × 10-8 (95% credible interval: 1.28 × 10-8-1.78 × 10-8) mutations/site/generation. Further, we found an unexpectedly low count of paternal mutations, and only a modest overrepresentation of mutations at CpG sites. Despite the surprising nature of these results, we found both the rate and spectrum to be robust to the manipulation of a wide range of computational filtering criteria. We also sequenced a technical replicate to estimate a false-negative and false-positive rate for our data and show that any point estimate of a de novo mutation rate should be considered with a large degree of uncertainty. For validation, we conducted an independent analysis of context-dependent substitution types for gray mouse lemur and five additional primate species for which de novo mutation rates have also been estimated. These comparisons revealed general consistency of the mutation spectrum between the pedigree-based and the substitution-rate analyses for all species compared.

Determinants of non-adherence to anti-TB treatment in high income, low TB incidence settings: a scoping review.

BACKGROUND: Improving adherence to anti-TB treatment is a public health priority in high-income, low incidence (HILI) regions. We conducted a scoping review to identify reported determinants of non-adherence in HILI settings.METHODS: Key terms related to TB, treatment and adherence were used to search MEDLINE, EMBASE, Web of Science, PsycINFO and CINAHL in June 2019. Quantitative studies examining determinants (demographic, clinical, health systems or psychosocial) of non-adherence to anti-TB treatment in HILI settings were included.RESULTS: From 10,801 results, we identified 24 relevant studies from 10 countries. Definitions and methods of assessing adherence were highly variable, as were documented levels of non-adherence (0.9-89%). Demographic factors were assessed in all studies and clinical factors were frequently assessed (23/24). Determinants commonly associated with non-adherence were homelessness, incarceration, and alcohol or drug misuse. Health system (8/24) and psychosocial factors (6/24) were less commonly evaluated.CONCLUSION: Our review identified some key factors associated with non-adherence to anti-TB treatment in HILI settings. Modifiable determinants such as psychosocial factors are under-evidenced and should be further explored, as these may be better targeted by adherence support. There is an urgent need to standardise definitions and measurement of adherence to more accurately identify the strongest determinants.

The Canadian Neuromuscular Disease Registry 2010-2019: A Decade of Facilitating Clinical Research Througha Nationwide, Pan-NeuromuscularDisease Registry.

We report the recruitment activities and outcomes of a multi-disease neuromuscular patient registry in Canada. The Canadian Neuromuscular Disease Registry (CNDR) registers individuals across Canada with a confirmed diagnosis of a neuromuscular disease. Diagnosis and contact information are collected across all diseases and detailed prospective data is collected for 5 specific diseases: Amyotrophic Lateral Sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), Myotonic Dystrophy (DM), Limb Girdle Muscular Dystrophy (LGMD), and Spinal Muscular Atrophy (SMA). Since 2010, the CNDR has registered 4306 patients (1154 pediatric and 3148 adult) with 91 different neuromuscular diagnoses and has facilitated 125 projects (73 academic, 3 not-for-profit, 3 government, and 46 commercial) using registry data. In conclusion, the CNDR is an effective and productive pan-neuromuscular registry that has successfully facilitated a substantial number of studies over the past 10 years.

Neonatal outcomes following previable prelabour rupture of membranes before 23 weeks of gestation - A retrospective cohort study.

OBJECTIVE: To compare outcomes of hospitalized preterm infants following previable prelabour rupture of membranes (PPROM) at≤23 weeks of gestation. METHODS: Retrospective cohort study of preterm infants admitted for intensive care, between January 2006 and December 2016 following PPROM, was conducted. Short term clinical outcomes included severity of respiratory morbidity, length of hospital stay and mortality. Neurodevelopment in survivors was assessed using Bayley's Scales of Infant Development (3rd edition) at 24 months corrected age. RESULTS: A total of 82 preterm infants were admitted following PPROM at < 23 weeks and were grouped as: Group 1 (n = 28) with PPROM < 20 weeks and Group 2 (n = 54) with PPROM between 20-22 + 6 weeks. Median latency following PPROM was significantly longer in Group 1 infants [69(Interquartile range (IQR): 43-74; Range (R): 25-100 vs. 29(IQR: 10-53; R: 2-72) days, p < 0.001]. Median gestation at delivery was 27.4 weeks (Group 1) vs. 25.1 weeks (Group 2). Group 1 had a significantly higher incidence of oligohydramnios [13(46.4%) vs. 8(14.8%), p = 0.002], lower Apgar scores (<7) at 5 minutes [19(67.9%) vs. 24(44.4%), p = 0.044], increased pulmonary hypoplasia [13(46.4%) vs. 5(9.3%), p < 0.001], joint contractures [3(10.7%) vs. 0, p = 0.037] and mortality [10(35.7%) vs. 7(13.0%), p = 0.016]. Neurodevelopmental outcomes at 24 months corrected age were comparable in the 36 surviving infants (9/18 vs. 27/547). CONCLUSION: Morbidity and mortality is high in infants born after previable PPROM; specifically, in those with PPROM < 20 weeks although early childhood neurodevelopmental outcomes were comparable. Larger prospective studies focussing on long term neonatal outcomes are needed to confirm these findings.

Cryptic Patterns of Speciation in Cryptic Primates: Microendemic Mouse Lemurs and the Multispecies Coalescent.

Mouse lemurs (Microcebus) are a radiation of morphologically cryptic primates distributed throughout Madagascar for which the number of recognized species has exploded in the past two decades. This taxonomic revision has prompted understandable concern that there has been substantial oversplitting in the mouse lemur clade. Here, we investigate mouse lemur diversity in a region in northeastern Madagascar with high levels of microendemism and predicted habitat loss. We analyzed RADseq data with multispecies coalescent (MSC) species delimitation methods for two pairs of sister lineages that include three named species and an undescribed lineage previously identified to have divergent mtDNA. Marked differences in effective population sizes, levels of gene flow, patterns of isolation-by-distance, and species delimitation results were found among the two pairs of lineages. Whereas all tests support the recognition of the presently undescribed lineage as a separate species, the species-level distinction of two previously described species, M. mittermeieri and M. lehilahytsara is not supported-a result that is particularly striking when using the genealogical discordance index (gdi). Nonsister lineages occur sympatrically in two of the localities sampled for this study, despite an estimated divergence time of less than 1 Ma. This suggests rapid evolution of reproductive isolation in the focal lineages and in the mouse lemur clade generally. The divergence time estimates reported here are based on the MSC calibrated with pedigree-based mutation rates and are considerably more recent than previously published fossil-calibrated relaxed-clock estimates. We discuss the possible explanations for this discrepancy, noting that there are theoretical justifications for preferring the MSC estimates in this case. [Cryptic species; effective population size; microendemism; multispecies coalescent; speciation; species delimitation.].

Induction of Short-Term Sensitization by an Aversive Chemical Stimulus in Zebrafish Larvae.

Larval zebrafish possess a number of molecular and genetic advantages for rigorous biological analyses of learning and memory. These advantages have motivated the search for novel forms of memory in these animals that can be exploited for understanding the cellular and molecular bases of vertebrate memory formation and consolidation. Here, we report a new form of behavioral sensitization in zebrafish larvae that is elicited by an aversive chemical stimulus [allyl isothiocyanate (AITC)] and that persists for ≥30 min. This form of sensitization is expressed as enhanced locomotion and thigmotaxis, as well as elevated heart rate. To characterize the neural basis of this nonassociative memory, we used transgenic zebrafish expressing the fluorescent calcium indicator GCaMP6 (Chen et al., 2013); because of the transparency of larval zebrafish, we could optically monitor neural activity in the brain of intact transgenic zebrafish before and after the induction of sensitization. We found a distinct brain area, previously linked to locomotion, that exhibited persistently enhanced neural activity following washout of AITC; this enhanced neural activity correlated with the behavioral sensitization. These results establish a novel form of memory in larval zebrafish and begin to unravel the neural basis of this memory.