SARS-CoV-2 Antibody Prevalence among Industrial Livestock Operation Workers and Nearby Community Residents, North Carolina, 2021 to 2022.

Industrial livestock operations (ILOs), particularly processing facilities, emerged as centers of coronavirus disease 2019 (COVID-19) outbreaks in spring 2020. Confirmed cases of COVID-19 underestimate true prevalence. To investigate the prevalence of antibodies against SARS-CoV-2, we enrolled 279 participants in North Carolina from February 2021 to July 2022: 90 from households with at least one ILO worker (ILO), 97 from high-ILO intensity areas (ILO neighbors [ILON]), and 92 from metropolitan areas (metro). More metro (55.4%) compared to ILO (51.6%) and ILON participants (48.4%) completed the COVID-19 primary vaccination series; the median completion date was more than 4 months later for ILO compared to ILON and metro participants, although neither difference was statistically significant. Participants provided a saliva swab we analyzed for SARS-CoV-2 IgG using a multiplex immunoassay. The prevalence of infection-induced IgG (positive for nucleocapsid and receptor binding domain) was higher among ILO (63%) than ILON (42.9%) and metro (48.7%) participants (prevalence ratio [PR], 1.38; 95% confidence interval [CI], 1.06 to 1.80; reference category ILON and metro combined). The prevalence of infection-induced IgG was also higher among ILO participants than among an Atlanta health care worker cohort (PR, 2.45; 95% CI, 1.80 to 3.33) and a general population cohort in North Carolina (PRs, 6.37 to 10.67). The infection-induced IgG prevalence increased over the study period. Participants reporting not masking in public in the past 2 weeks had higher infection-induced IgG prevalence (78.6%) than participants reporting masking (49.3%) (PR, 1.59; 95% CI, 1.19 to 2.13). Lower education, more people per bedroom, Hispanic/Latino ethnicity, and more contact with people outside the home were also associated with higher infection-induced IgG prevalence. IMPORTANCE Few studies have measured COVID-19 seroprevalence in North Carolina, especially among rural, Black, and Hispanic/Latino communities that have been heavily affected. Antibody results show high rates of COVID-19 among industrial livestock operation workers and their household members. Antibody results add to evidence of health disparities related to COVID-19 by socioeconomic status and ethnicity. Associations between masking and physical distancing with antibody results also add to evidence of the effectiveness of these prevention strategies. Delays in the timing of receipt of COVID-19 vaccination reinforce the importance of dismantling vaccination barriers, especially for industrial livestock operation workers and their household members.

Risk factors for third-generation cephalosporin-resistant and extended-spectrum ß-lactamase-producing Escherichia coli carriage in domestic animals of semirural parishes east of Quito, Ecuador.

Extended-spectrum ß-lactamase (ESBL)-producing and other antimicrobial resistant (AR) Escherichia coli threaten human and animal health worldwide. This study examined risk factors for domestic animal colonization with ceftriaxone-resistant (CR) and ESBL-producing E. coli in semirural parishes east of Quito, Ecuador, where small-scale food animal production is common. Survey data regarding household characteristics, animal care, and antimicrobial use were collected from 304 households over three sampling cycles, and 1195 environmental animal fecal samples were assessed for E. coli presence and antimicrobial susceptibility. Multivariable regression analyses were used to assess potential risk factors for CR and ESBL-producing E. coli carriage. Overall, CR and ESBL-producing E. coli were detected in 56% and 10% of all fecal samples, respectively. The odds of CR E. coli carriage were greater among dogs at households that lived within a 5 km radius of more than 5 commercial food animal facilities (OR 1.72, 95% CI 1.15-2.58) and lower among dogs living at households that used antimicrobials for their animal(s) based on veterinary/pharmacy recommendation (OR 0.18, 95% CI 0.04-0.96). Increased odds of canine ESBL-producing E. coli carriage were associated with recent antimicrobial use in any household animal (OR 2.69, 95% CI 1.02-7.10) and purchase of antimicrobials from pet food stores (OR 6.83, 95% CI 1.32-35.35). Food animals at households that owned more than 3 species (OR 0.64, 95% CI 0.42-0.97), that used antimicrobials for growth promotion (OR 0.41, 95% CI 0.19-0.89), and that obtained antimicrobials from pet food stores (OR 0.47, 95% CI 0.25-0.89) had decreased odds of CR E. coli carriage, while food animals at households with more than 5 people (OR 2.22, 95% CI 1.23-3.99) and located within 1 km of a commercial food animal facility (OR 2.57, 95% CI 1.08-6.12) had increased odds of ESBL-producing E. coli carriage. Together, these results highlight the complexity of antimicrobial resistance among domestic animals in this setting.

Human iPSC-derived fallopian tube organoids with BRCA1 mutation recapitulate early-stage carcinogenesis.

Germline pathogenic mutations in BReast CAncer (BRCA1) genes are thought to drive normal fallopian tube epithelial (FTE) cell transformation to high-grade serous ovarian cancer. No human models capture the sequence of events for disease initiation and progression. Here, we generate induced pluripotent stem cells (iPSCs) from healthy individuals and young ovarian cancer patients with germline pathogenic BRCA1 mutations (BRCA1mut). Following differentiation into FTE organoids, BRCA1mut lines exhibit cellular abnormalities consistent with neoplastic transformation compared to controls. BRCA1mut organoids show an increased production of cancer-specific proteins and survival following transplantation into mice. Organoids from women with the most aggressive ovarian cancer show the greatest pathology, indicating the potential value to predict clinical severity prior to disease onset. These human FTE organoids from BRCA1mut carriers provide a faithful physiological in vitro model of FTE lesion generation and early carcinogenesis. This platform can be used for personalized mechanistic and drug screening studies.

Social and Environmental Determinants of Community-Acquired Antimicrobial-Resistant Escherichia coli in Children Living in Semirural Communities of Quito, Ecuador.

Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL), a family of bacteria that includes Escherichia coli, have emerged as a global health threat. This study examined risks associated with carriage of third-generation cephalosporin-resistant (3GC-R) E. coli, including ESBL-producing, multidrug-resistant, and extensively drug-resistant (XDR) strains in children living in semirural parishes of Quito, Ecuador. We conducted a longitudinal study with two cycles of sampling (N = 374, N = 366) that included an analysis of child fecal samples and survey questions relating to water, sanitation, and hygiene, socioeconomic status, household crowding, and animal ownership. We used multivariate regression models to assess risk factors associated with a child being colonized. Across the two cycles, 18.4% (n = 516) of the 3GC-R isolates were ESBL-producing E. coli, and 40.3% (n = 516) were XDR E. coli. Children living in households that owned between 11 and 20 backyard animals had an increased odds of being colonized with XDR E. coli (odds ratio [OR] = 1.94, 95% confidence interval [CI]: 1.05-3.60) compared with those with no animals. Households that reported smelling odors from commercial poultry had increased odds of having a child positive for XDR E. coli (OR = 1.72, 95% CI: 1.11-2.66). Our results suggest that colonization of children with antimicrobial-resistant E. coli is influenced by exposure to backyard and commercial livestock and poultry. Future studies should consider community-level risk factors because child exposures to drug-resistant bacteria are likely influenced by neighborhood and regional risk factors.

Caretaker knowledge, attitudes, and practices (KAP) and carriage of extended-spectrum beta-lactamase-producing E. coli (ESBL-EC) in children in Quito, Ecuador.

BACKGROUND: The rapid spread of extended-spectrum beta-lactamase-producing E. coli (ESBL-EC) is an urgent global health threat. We examined child caretaker knowledge, attitudes, and practices (KAP) towards proper antimicrobial agent use and whether certain KAP were associated with ESBL-EC colonization of their children. METHODS: Child caretakers living in semi-rural neighborhoods in peri-urban Quito, Ecuador were visited and surveyed about their KAP towards antibiotics. Fecal samples from one child (less than 5 years of age) per household were collected at two time points between July 2018 and May 2019 and screened for ESBL-EC. A repeated measures analysis with logistic regression was used to assess the relationship between KAP levels and child colonization with ESBL-EC. RESULTS: We analyzed 740 stool samples from 444 children living in households representing a range of environmental conditions. Of 374 children who provided fecal samples at the first household visit, 44 children were colonized with ESBL-EC (11.8%) and 161 were colonized with multidrug-resistant E. coli (43%). The prevalences of ESBL-EC and multidrug-resistant E. coli were similar at the second visit (11.2% and 41.3%, respectively; N = 366). Only 8% of caretakers knew that antibiotics killed bacteria but not viruses, and over a third reported that they "always" give their children antibiotics when the child's throat hurts (35%). Few associations were observed between KAP variables and ESBL-EC carriage among children. The odds of ESBL-EC carriage were 2.17 times greater (95% CI: 1.18-3.99) among children whose caregivers incorrectly stated that antibiotics do not kill bacteria compared to children whose caregivers correctly stated that antibiotics kill bacteria. Children from households where the caretaker answered the question "When your child's throat hurts, do you give them antibiotics?" with "sometimes" had lower odds of ESBL-EC carriage than those with a caretaker response of "never" (OR 0.48, 95% CI 0.27-0.87). CONCLUSION: Caregivers in our study population generally demonstrated low knowledge regarding appropriate use of antibiotics. Our findings suggest that misinformation about the types of infections (i.e. bacterial or viral) antibiotics should be used for may be associated with elevated odds of carriage of ESBL-EC. Understanding that using antibiotics is appropriate to treat infections some of the time may reduce the odds of ESBL-EC carriage. Overall, however, KAP measures of appropriate use of antibiotics were not strongly associated with ESBL-EC carriage. Other individual- and community-level environmental factors may overshadow the effect of KAP on ESBL-EC colonization. Intervention studies are needed to assess the true effect of improving KAP on laboratory-confirmed carriage of antimicrobial resistant bacteria, and should consider community-level studies for more effective management.

Phonetic basis of phonemic paraphasias in aphasia: Evidence for cascading activation.

Phonemic paraphasias are a common presenting symptom in aphasia and are thought to reflect a deficit in which selecting an incorrect phonemic segment results in the clear-cut substitution of one phonemic segment for another. The current study re-examines the basis of these paraphasias. Seven left hemisphere-damaged aphasics with a range of left hemisphere lesions and clinical diagnoses including Broca's, Conduction, and Wernicke's aphasia, were asked to produce syllable-initial voiced and voiceless fricative consonants, [z] and [s], in CV syllables followed by one of five vowels [i e a o u] in isolation and in a carrier phrase. Acoustic analyses were conducted focusing on two acoustic parameters signaling voicing in fricative consonants: duration and amplitude properties of the fricative noise. Results show that for all participants, regardless of clinical diagnosis or lesion site, phonemic paraphasias leave an acoustic trace of the original target in the error production. These findings challenge the view that phonemic paraphasias arise from a mis-selection of phonemic units followed by its correct implementation, as traditionally proposed. Rather, they appear to derive from a common mechanism with speech errors reflecting the co-activation of a target and competitor resulting in speech output that has some phonetic properties of both segments.

Neural systems underlying the influence of sound shape properties of the lexicon on spoken word production: do fMRI findings predict effects of lesions in aphasia?

Previous behavioral work has shown that the phonetic realization of words in spoken word production is influenced by sound shape properties of the lexicon. A recent fMRI study (Peramunage, Blumstein, Myers, Goldrick, & Baese-Berk, 2011) showed that this influence of lexical structure on phonetic implementation recruited a network of areas that included the supramarginal gyrus (SMG) extending into the posterior superior temporal gyrus (pSTG) and the inferior frontal gyrus (IFG). The current study examined whether lesions in these areas result in a concomitant functional deficit. Ten individuals with aphasia and 8 normal controls read words aloud in which half had a voiced stop consonant minimal pair (e.g. tame; dame), and the other half did not (e.g. tooth; (*)dooth). Voice onset time (VOT) analysis of the initial voiceless stop consonant revealed that aphasic participants with lesions including the IFG and/or the SMG behaved as did normals, showing VOT lengthening effects for minimal pair words compared to non-minimal pair words. The failure to show a functional deficit in the production of VOT as a function of the lexical properties of a word with damage in the IFG or SMG suggests that fMRI findings do not always predict effects of lesions on behavioral deficits in aphasia. Nonetheless, the pattern of production errors made by the aphasic participants did reflect properties of the lexicon, supporting the view that the SMG and IFG are part of a lexical network involved in spoken word production.

Nasal consonant production in Broca's and Wernicke's aphasics: speech deficits and neuroanatomical correlates.

The present study investigated the articulatory implementation deficits of Broca's and Wernicke's aphasics and their potential neuroanatomical correlates. Five Broca's aphasics, two Wernicke's aphasics, and four age-matched normal speakers produced consonant-vowel-(consonant) real word tokens consisting of [m, n] followed by [i, e, a, o, u]. Three acoustic measures were analyzed corresponding to different properties of articulatory implementation: murmur duration (a measure of timing), amplitude of the first harmonic at consonantal release (a measure of articulatory coordination), and murmur amplitude over time (a measure of laryngeal control). Results showed that Broca's aphasics displayed impairments in all of these parameters, whereas Wernicke's aphasics only exhibited greater variability in the production of two of the parameters. The lesion extent data showed that damage in either Broca's area or the insula cortex was not predictive of the severity of the speech output impairment. Instead, lesions in the upper and lower motor face areas and the supplementary motor area resulted in the most severe implementation impairments. For the Wernicke's aphasics, the posterior areas (superior marginal gyrus, parietal, and sensory) appear to be involved in the retrieval and encoding of lexical forms for speech production, resulting in increased variability in speech production.

The nature of speech production impairments in anterior aphasics: an acoustic analysis of voicing in fricative consonants.

This study investigated the acoustic characteristics of voicing in English fricative consonants produced by anterior aphasics and the effects of phonetic context on these characteristics. Three patients produced voiced and voiceless fricative-vowel syllables in isolation, following a voiced velar stop, and following a voiceless velar stop. Acoustic analyses were conducted of the amplitude and patterning of glottal excitation, as well as fricative noise duration. Results showed that, although the patients are able to coordinate the articulatory gestures for voicing in fricative consonants, they demonstrated abnormal patterns of glottal excitation in the amplitude measures, owing to weaker amplitudes of glottal excitation in voiced fricatives. Context effects failed to emerge because of dysfluent speech. These results suggest that the locus of the speech production deficit of anterior aphasics is not at the higher stages of phoneme selection or planning but rather in articulatory implementation, one related to laryngeal control.