Bovine Alphaherpesvirus 1, Bovine Alphaherpesvirus 5 and Bubaline Alphaherpesvirus 1 in Palatine Tonsils from Water Buffaloes in Northern Brazil and Possible Links with the Origin of Bovine Alphaherpesvirus Type 5.

Herpesviruses are significant pathogens of ruminants. In water buffaloes (Bubalus bubalis), however, herpesviruses have not been thoroughly studied. Although bubaline alphaherpesvirus 1 (BuAHV1) and bovine alphaherpesvirus 1 (BoAHV1) have already been recovered from water buffaloes, to date, no reports on the occurrence of bovine alphaherpesvirus 5 (BoAHV5) in these animals have been published. Therefore, the aim of this study was to search for BuAHV1, BoAHV1, and BoAHV5 in palatine tonsils of apparently healthy water buffaloes from the Pará state, Northern Brazil. Tissue samples of tonsils (n = 293) were screened by a nested PCR (nPCR) targeting a region of UL44 (gC coding gene), followed by sequencing, to detect and differentiate between the viral types. Viral genome segments were detected in 18 out of 293 (6.1%) of the palatine tonsil samples. Two animals carried genomes of BoAHV1 only, eleven animals carried BoAHV5 genomes only, and four animals carried BuAHV1 only. Another animal had both BoAHV1 and BoAHV5 genomes in its tonsils. No infectious virus could be recovered from any of the samples. The BuAHV1 sequences identified here were more closely related to BuAHV1 genomes identified in India. Phylogenetic analyses suggested a closer relationship between the recovered BoAHV5 and BuAHV1 genomes. Therefore, evidence is provided here to confirm that not only BoAHV1 and BuAHV1, but also BoAHV5, can infect water buffaloes. This report highlights (i) the first detection of BoAHV5 in water buffaloes and (ii) the occurrence of coinfections with BoAHV1 and BoAHV5 in that species. Such findings and the similarity of BoAHV5 to Indian herpesvirus genomes suggest that the origin of type 5 may be linked to recombinations between bovine and bubaline herpesviruses within bubalines, since the scenario for generation of recombinants in buffaloes is potentially present.

Safe Injection Self-Efficacy is Associated with HCV and HIV Seropositivity Among People Who Inject Drugs in the San Diego-Tijuana Border Region.

Safe injection self-efficacy (SISE) is negatively associated with injection risk behaviors among people who inject drugs (PWID) but has not been examined in differing risk environments. We compared responses to a validated SISE scale between PWID in San Diego, California and Tijuana, Mexico, and examine correlates of SISE among PWID in Tijuana. PWID were recruited via street outreach for a longitudinal cohort study from October 2020-September 2021. We compared SISE scale items by city. Due to low variability in SISE scores among San Diego residents, we restricted analysis of factors associated with SISE to Tijuana residents and identified correlates of SISE score levels (low, medium, high) using ordinal logistic regression. Of 474 participants, most were male (74%), Latinx (78%) and Tijuana residents (73%). Mean age was 44. Mean SISE scores among San Diego residents were high (3.46 of 4 maximum) relative to Tijuana residents (mean: 1.93). Among Tijuana residents, White race and having previously resided in San Diego were associated with higher SISE scores. HCV and HIV seropositivity, homelessness, fentanyl use, polysubstance co-injection, and greater injection frequency were associated with lower SISE scores. We found profound inequalities between Tijuana and San Diego SISE, likely attributable to differential risk environments. Associations with fentanyl and polysubstance co-injection, injection frequency, and both HIV and HCV seropositivity suggest that SISE contribute to blood-borne infection transmission risks in Tijuana. SISE reflects an actionable intervention target to reduce injection risk behaviors, but structural interventions are required to change the risk environment.

RESUMEN: La autoeficacia de inyección segura (SISE, por sus siglas en inglés) se asocia negativamente con conductas de riesgo de inyección entre las personas que se inyectan drogas (PWID, por sus siglas en inglés), pero no se ha examinado en diferentes entornos de riesgo. Comparamos las respuestas a una escala validada de SISE entre PWID en San Diego, California, y Tijuana, México, y examinamos los correlatos de SISE entre PWID en Tijuana. Participantes fueron reclutados por medio de alcance callejero para un estudio de cohorte longitudinal entre octubre 2020 ­septiembre de 2021. Comparamos los ítems de la escala SISE por ciudad. Debido a la baja variabilidad en los puntajes SISE entre los residentes de San Diego, restringimos el análisis de factores asociados con SISE a los residentes de Tijuana e identificamos factores correlacionados con niveles de SISE (bajo, medio, alto) mediante regresión logística ordinal. De 474 participantes, la mayoría eran hombres (74%), latinx (78%) y residentes de Tijuana (73%). La edad promedio fue de 44 años. Los puntajes medios de SISE entre los residentes de San Diego fueron altos (3.46 de un máximo de 4) en comparación con los residentes de Tijuana (media: 1.93). Entre los residentes de Tijuana, la raza blanca y haber residido previamente en San Diego se asociaron con puntajes más altos de SISE. La seropositividad para HCV y VIH, la falta de vivienda, el uso de fentanilo, la co-inyección de múltiples sustancias y una mayor frecuencia de inyecciónes se asociaron con puntajes más bajos de SISE. Encontramos profundas desigualdades entre SISE en Tijuana y San Diego, probablemente atribuibles a diferentes entornos de riesgo. Las asociaciones con fentanilo y la co-inyección de múltiples sustancias, la frecuencia de inyección y la seropositividad tanto para VIH como para HCV sugieren que SISE contribuye a los riesgos de transmisión de infecciones transmitidas por la sangre en Tijuana. SISE refleja un objetivo de intervención accionable para reducir las conductas de riesgo de inyección, pero se requieren intervenciones estructurales para cambiar el entorno de riesgo.

Smoking characteristics and years since quitting smoking of US adults diagnosed with lung and bladder cancer: A national health and nutrition examination survey analysis

ABSTRACT Purpose: Smoking is a recognized risk factor for bladder BC and lung cancer LC. We investigated the enduring risk of BC after smoking cessation using U.S. national survey data. Our analysis focused on comparing characteristics of LC and BC patients, emphasizing smoking status and the latency period from smoking cessation to cancer diagnosis in former smokers. Materials and Methods: We analyzed data from the National Health and Examination Survey (2003-2016), identifying adults with LC or BC history. Smoking status (never, active, former) and the interval between quitting smoking and cancer diagnosis for former smokers were assessed. We reported descriptive statistics using frequencies and percentages for categorical variables and median with interquartile ranges (IQR) for continuous variables. Results: Among LC patients, 8.9% never smoked, 18.9% active smokers, and 72.2% former smokers. Former smokers had a median interval of 8 years (IQR 2-12) between quitting and LC diagnosis, with 88.3% quitting within 0-19 years before diagnosis. For BC patients, 26.8% never smoked, 22.4% were active smokers, and 50.8% former smokers. Former smokers had a median interval of 21 years (IQR 14-33) between quitting and BC diagnosis, with 49.3% quitting within 0-19 years before diagnosis. Conclusions: BC patients exhibit a prolonged latency period between smoking cessation and cancer diagnosis compared to LC patients. Despite smoking status evaluation in microhematuria, current risk stratification models for urothelial cancer do not incorporate it. Our findings emphasize the significance of long-term post-smoking cessation surveillance and advocate for integrating smoking history into future risk stratification guidelines.

Resurgence of human respiratory syncytial virus during COVID-19 pandemic in Southern Brazil.

Respiratory Syncytial Virus (RSV) is an important cause of respiratory infection in humans. Severe cases are common in children ≤2 years old, immunocompromised individuals, and the elderly. In 2020, RSV infection reduced in Rio Grande do Sul (RS), southern Brazil; however, in 2021 resurgence of RSV was observed. This study analyzed epidemiological and genetic features of RSV infection cases reported in 2021 in RS. Nasopharyngeal samples collected from individuals with respiratory infection negative for SARS-CoV-2, Influenza A and B viruses were assessed for the presence of RSV by real time RT-qPCR. RSV-A and RSV-B genomic sequencing and phylogenetic reconstructions were performed for genotyping and clade characterization. Among 21,035 respiratory samples analyzed, 2,947 were positive for RSV, 947 of which were hospitalized patients. Positive cases were detected year-round, with the highest number in June-July (winter). Children <1 year comprised 56.28% (n = 533) of the hospitalized patients infected with RSV, whereas 14.46% (n = 137) were individuals >60 years. Of a total of 361 deaths, 14.68% (n = 53) were RSV positive, mostly patients >60 years old (73.58%, n = 39). Chronic kidney disease, cardiopathy, Down syndrome and neurological diseases were associated with RSV infection. RSV-A was identified in 58.5% (n = 117/200) of the patients, and RSV-B in 41.5% (n = 83/200). Of 95 RSV genomes recovered from SARI cases, 66 were RSV-A GA.2.3.5 genotype, while 29 were RSV-B GB.5.0.5a genotype. This study provides epidemiological and molecular data on RSV cases in RS during the COVID-19 pandemic and highlights that investigation of different respiratory viruses is essential for decision-making and disease prevention and control measures.

Smoking characteristics and years since quitting smoking of US adults diagnosed with lung and bladder cancer: A national health and nutrition examination survey analysis.

PURPOSE: Smoking is a recognized risk factor for bladder BC and lung cancer LC. We investigated the enduring risk of BC after smoking cessation using U.S. national survey data. Our analysis focused on comparing characteristics of LC and BC patients, emphasizing smoking status and the latency period from smoking cessation to cancer diagnosis in former smokers. MATERIALS AND METHODS: We analyzed data from the National Health and Examination Survey (2003-2016), identifying adults with LC or BC history. Smoking status (never, active, former) and the interval between quitting smoking and cancer diagnosis for former smokers were assessed. We reported descriptive statistics using frequencies and percentages for categorical variables and median with interquartile ranges (IQR) for continuous variables. RESULTS: Among LC patients, 8.9% never smoked, 18.9% active smokers, and 72.2% former smokers. Former smokers had a median interval of 8 years (IQR 2-12) between quitting and LC diagnosis, with 88.3% quitting within 0-19 years before diagnosis. For BC patients, 26.8% never smoked, 22.4% were active smokers, and 50.8% former smokers. Former smokers had a median interval of 21 years (IQR 14-33) between quitting and BC diagnosis, with 49.3% quitting within 0-19 years before diagnosis. CONCLUSIONS: BC patients exhibit a prolonged latency period between smoking cessation and cancer diagnosis compared to LC patients. Despite smoking status evaluation in microhematuria, current risk stratification models for urothelial cancer do not incorporate it. Our findings emphasize the significance of long-term post-smoking cessation surveillance and advocate for integrating smoking history into future risk stratification guidelines.

New Classification for Pediatric Proximal Fifth Metatarsal Fractures.

Proximal fifth metatarsal fractures are the most common foot fractures in children. Attempts to classify these injuries are misapplied and inadequately predict outcomes. This is the first study to identify factors associated with healing in pediatric fifth metatarsal fractures. In this retrospective cohort study (N = 305), proximal fifth metatarsal fractures were classified on radiographs by location on the bone, alignment (transverse or oblique), displacement (>2 mm), and completion through the bone. Based on the literature, they were secondarily sorted by category: apophyseal, intra-articular metaphyseal, extra-articular metaphyseal, and diaphyseal. Primary outcomes included times to healing, indicated by clinical symptoms, immobilization, and return to sports, as well as radiographic callus formation, bridging, and remodeling. Healing times were compared by ANOVA and linear regression. Location had a significant effect on times of immobilization and return to sports, but alignment, displacement, and completion were not associated with healing. When re-classified, the categories were also associated with immobilization and return to sports. Apophyseal fractures healed fastest and diaphyseal fractures required the most time to heal. There was no difference between extra- and intra-articular fractures. For every year of age, symptoms resolved about 2 days sooner. Neither gender nor body mass index (BMI) was positively or negatively associated with healing times. In conclusion, classifying fractures by apophyseal, metaphyseal, and diaphyseal is the most concise, accurate, and useful system. This is the largest series of nonoperatively treated proximal fifth metatarsal fractures in children and a robust standard to which surgical management can be compared.

Introduction, Dispersal, and Predominance of SARS-CoV-2 Delta Variant in Rio Grande do Sul, Brazil: A Retrospective Analysis.

Mutations in the SARS-CoV-2 genome can alter the virus' fitness, leading to the emergence of variants of concern (VOC). In Brazil, the Gamma variant dominated the pandemic in the first half of 2021, and from June onwards, the first cases of Delta infection were documented. Here, we investigate the introduction and dispersal of the Delta variant in the RS state by sequencing 1077 SARS-CoV-2-positive samples from June to October 2021. Of these samples, 34.7% were identified as Gamma and 65.3% as Delta. Notably, 99.2% of Delta sequences were clustered within the 21J lineage, forming a significant Brazilian clade. The estimated clock rate was 5.97 × 10-4 substitutions per site per year. The Delta variant was first reported on 17 June in the Vinhedos Basalto microregion and rapidly spread, accounting for over 70% of cases within nine weeks. Despite this, the number of cases and deaths remained stable, possibly due to vaccination, prior infections, and the continued mandatory mask use. In conclusion, our study provides insights into the Delta variant circulating in the RS state, highlighting the importance of genomic surveillance for monitoring viral evolution, even when the impact of new variants may be less severe in a given region.

Lack of spontaneous typical seizures during intracranial monitoring with stereo-electroencephalography.

OBJECTIVE: In the presurgical evaluation of patients with drug-resistant epilepsy (DRE), occasionally, patients do not experience spontaneous typical seizures (STS) during a stereo-electroencephalography (SEEG) study, which limits its effectiveness. We sought to identify risk factors for patients who did not have STS during SEEG and to analyze the clinical outcomes for this particular set of patients. METHODS: We conducted a retrospective analysis of all patients with DRE who underwent depth electrode implantation and SEEG recordings between January 2013 and December 2018. RESULTS: SEEG was performed in 155 cases during this period. 11 (7.2%) did not experience any clinical seizures (non-STS group), while 143 experienced at least one patient-typical seizure during admission (STS group). No significant differences were found between STS and non-STS groups in terms of patient demographics, lesional/non-lesional epilepsy ratio, pre-SEEG seizure frequency, number of ASMs used, electrographic seizures or postoperative seizure outcome in those who underwent resective surgery. Statistically significant differences were found in the average number of electrodes implanted (7.0 in the non-STS group vs. 10.2 in STS), days in Epilepsy Monitoring Unit (21.8 vs. 12.8 days) and the number of cases that underwent resective surgery following SEEG (27.3% vs. 60.8%), respectively. The three non-STS patients (30%) who underwent surgery, all had their typical seizures triggered during ECS studies. Three cases were found to have psychogenic non-epileptic seizures. None of the patients in the non-STS group were offered neurostimulation devices. Five of the non-STS patients experienced transient seizure improvement following SEEG. SIGNIFICANCE: We were unable to identify any factors that predicted lack of seizures during SEEG recordings. Resective surgery was only offered in cases where ECS studies replicated patient-typical seizures. Larger datasets are required to be able to identify factors that predict which patients will fail to develop seizures during SEEG.

Peripheral Activation of Formyl Peptide Receptor 2/ALX by Electroacupuncture Alleviates Inflammatory Pain by Increasing Interleukin-10 Levels and Catalase Activity in Mice.

In the context of the electroacupuncture (EA) neurobiological mechanisms, we have previously demonstrated the involvement of formyl peptide receptor 2 (FPR2/ALX) in the antihyperalgesic effect of EA. The present study investigated the involvement of peripheral FPR2/ALX in the antihyperalgesic effect of EA on inflammatory cytokines levels, oxidative stress markers and antioxidant enzymes in an animal model of persistent inflammatory pain. Male Swiss mice underwent intraplantar (i.pl.) injection with complete Freund's adjuvant (CFA). Mechanical hyperalgesia was assessed with von Frey monofilaments. Animals were treated with EA (2/10 Hz, ST36-SP6, 20 minutes) for 4 consecutive days. From the first to the fourth day after CFA injection, animals received i.pl. WRW4 (FPR2/ALX antagonist) or saline before EA. Levels of inflammatory cytokines (TNF, IL-6, IL-4 and IL-10), antioxidant enzymes (catalase and superoxide dismutase), oxidative stress markers (TBARS, protein carbonyl, nitrite/nitrate ratio), and myeloperoxidase activity were measured in paw tissue samples. As previously demonstrated, i.pl. injection of the FPR2/ALX antagonist prevented the antihyperalgesic effect induced by EA. Furthermore, animals treated with EA showed higher levels of IL-10 and catalase activity in the inflamed paw, and these effects were prevented by the antagonist WRW4. EA did not change levels of TNF and IL-6, SOD and MPO activity, and oxidative stress markers. Our work demonstrates that the antihyperalgesic effect of EA on CFA-induced inflammatory pain could be partially associated with higher IL-10 levels and catalase activity, and that these effects may be dependent, at least in part, on the activation of peripheral FPR2/ALX.

First Three Years' Experience of Mucopolysaccharidosis Type-I Newborn Screening in California.

OBJECTIVE: To report on the first 3 years of mucopolysaccharidosis type I (MPS I) newborn screening (NBS) in the large and diverse state of California. STUDY DESIGN: The California Genetic Disease Screening Program began universal NBS for MPS I on August 29, 2018. The screening uses a 2-tiered approach: an α-L-iduronidase (IDUA) enzyme activity assay followed by DNA sequencing for variants in the IDUA gene. RESULTS: As of August 29, 2021, 1 295 515 California newborns were screened for MPS I. In tier 1 of screening, 329 (0.025%) had an IDUA enzyme measurement below the cutoff and underwent tier-2 IDUA DNA sequencing. After tier 2, 146 (0.011%) newborns were screen positive, all of whom were referred to a metabolic Special Care Center for follow-up. After long-term follow-up, 7 cases were resolved as severe MPS I (Hurler syndrome) and 2 cases as attenuated MPS I for an MPS I birth prevalence of 1/143 946. DNA sequencing identified 107 unique IDUA variants among a total of 524 variants; 65% were known pseudodeficiency alleles, 25% were variants of uncertain significance, and 10% were pathogenic variants. CONCLUSIONS: As a result of a 2-tiered NBS approach, 7 newborns diagnosed with Hurler syndrome had received early treatment for MPS I. Continuation of California's long-term follow-up program will be crucial for further understanding the complex genotype-phenotype relationships of MPS I.

Survey and Molecular Characterization of Sarcocystidae protozoa in Wild Cricetid Rodents from Central and Southern Chile.

In Chile, studies of parasites from the family Sarcocystidae (Apicomplexa) have mostly been related to domestic animals. We aimed to assess the presence of Sarcocystidae taxa in cricetid rodents from Central and Southern Chile. We studied 207 rodents, encompassing six species, from 13 localities. We isolated DNA from tissue samples, amplified the Sarcocystidae 18S rRNA gene with polymerase chain reaction, and performed phylogenetic analyses using maximum likelihood and Bayesian inferences. In addition, we examined blood smears and performed histological studies in organs from Sarcocystidae DNA-positive animals. Three specimens were DNA-positive and three genotypes were retrieved and named: Sarcocystis sp. P61, related to Sarcocystis strixi, was detected in two Abrothrix olivacea. Toxoplasmatinae gen. sp. P99 was retrieved from those same two specimens, and was related to Toxoplasma and other genera, although it branched independently. Besnoitia sp. R34 was detected in one Abrothrix hirta, and was clustered with congeneric species associated with rodents. No protozoa were found during microscopic studies; thus, it was not possible to confirm parasitic interactions rather than accidental encounters. However, the close relatedness of the retrieved genotypes to parasites of rodents supports the hypothesis of host-parasite associations. All three genotypes are suggested as potential new taxa, including a putative new genus.

Neurotrophic keratopathy following rhegmatogenous retinal detachment surgery.

OBJECTIVE: To describe clinical characteristics and visual outcomes of eyes developing neurotrophic keratopathy (NK) following rhegmatogenous retinal detachment (RRD) repair. METHODS: All eyes with NK at Wills Eye Hospital following RRD repair from June 1, 2011, to December 1, 2020 were included. Patients with prior ocular procedures (other than cataract surgery), herpetic keratitis, and diabetes mellitus were excluded. RESULTS: During the study period, 241 patients were diagnosed with NK, and 8179 eyes underwent RRD surgery, giving a 9-year prevalence rate of 0.1% (95% CI, 0.1%-0.2%). Mean age was 53.4 ± 16.6 years during RRD repair and 56.5 ± 13.4 years during NK diagnosis. Mean time to NK diagnosis was 3.0 ± 5.6 years (range, 6 days to 18.8 years). Mean visual acuity before NK was 1.10 ± 0.56 logMAR (20/252 Snellen), and it was 1.01 ± 0.62 logMAR (20/205 Snellen) at final visit (p = 0.75). Six eyes (54.5%) developed NK <1 year following RRD surgery. Mean final visual acuity was 1.01 ± 0.53 logMAR (20/205 Snellen) in this group versus 1.01 ± 0.78 logMAR (20/205 Snellen) in the delayed NK group (p = 1.00). CONCLUSIONS: NK may present acutely or up to several years following surgery, with severity of corneal defects ranging from stage 1 to stage 3 NK. Surgeons should be mindful of the potential for this rare complication following RRD repair.

Disasters and corruption: public expectations and tolerance-evidence from Mexico.

Disaster corruption is a vexing problem, damaging state legitimacy and exacerbating human suffering. Mexico has a history of both major disasters and persistently high levels of corruption. A magnitude 7.1 earthquake in 2017 provided an opportunity to study change over time in expectations and tolerance of corruption in disaster relief. Twenty years earlier, Mexico City residents expected, on average, essentially three out of 10 hypothetical trucks loaded with humanitarian assistance to be lost to corruption but expressed near zero tolerance of such conduct. By 2018-19, Mexico City residents expected more than one-half of all relief, six out of 10 trucks, to be stolen, and could tolerate three out of 10 trucks being pilfered. Similar results were found at the national level. Hence, Mexicans appear to be giving up on the state. Addressing corruption in disaster risk reduction and humanitarian relief specifically might provide a template for improving public trust across other state institutions.

PD-L1 gene amplification and focality: relationship with protein expression.

PD-L1 (CD274) amplification occurs in a small subset of malignancies and may predict anti-PD-1/PD-L1 immunotherapy responsiveness. We hypothesized that both copy number (CN) and focality of cancer-related PD-L1 amplifications impact protein expression, and, thus, analyzed solid tumors that underwent comprehensive genomic profiling between March 2016 and February 2022 at Foundation Medicine. PD-L1 CN alterations were detected using a comparative genomic hybridization-like method. PD-L1 CN changes were correlated with PD-L1 protein expression (DAKO 22C3 antibody) by immunohistochemistry (IHC). Overall, 60,793 samples were analyzed (most frequent histologies: lung adenocarcinoma (20%), colon adenocarcinoma (12%), lung squamous carcinoma (8%)). Using a definition of CD274 CN ≥ specimen ploidy +4 (6 copies), 1.21% of tumors (738/60,793) were PD-L1 amplified. Focality category distribution was as follows: <0.1 mB (n=18 (2.4%)), ≥0.1 to <4 mB (n=230 (31.1%)), ≥4 to <20 mB (n=310 (42%)), ≥20mB (n=180 (24.4%)). Lower levels of PD-L1 amplification (below specimen ploidy +4) were more frequently non-focal amplifications compared to higher levels. In addition, more focal amplification (<0.1 mB) correlated with higher PD-L1 IHC expression. Median tumor proportion score (TPS) for samples with PD-L1 amplification (ploidy ≥+4) according to focality were 87.5% (<0.1 mB), 80% (≥0.1 to <4 mB), 40% (≥4 to <20 mB), 1% (≥20mB). In specimens with PD-L1 ploidy less than +4, but highly focal (<0.1 mB), the 75th percentile of PD-L1 expression by TPS was 80%. Conversely, non-focal (≥20 mB) PD-L1 amplification (ploidy ≥+4) can present high PD-L1 expression (TPS≥50%), albeit infrequently (0.09% of our cohort). In conclusion, PD-L1 expression measured by IHC is influenced by PD-L1 amplification level and focality. Further correlation between amplification, focality, protein expression and therapeutic outcome for PD-L1 and other targetable genes warrants exploration.

ATM inhibition drives metabolic adaptation via induction of macropinocytosis.

Macropinocytosis is a nonspecific endocytic process that may enhance cancer cell survival under nutrient-poor conditions. Ataxia-Telangiectasia mutated (ATM) is a tumor suppressor that has been previously shown to play a role in cellular metabolic reprogramming. We report that the suppression of ATM increases macropinocytosis to promote cancer cell survival in nutrient-poor conditions. Combined inhibition of ATM and macropinocytosis suppressed proliferation and induced cell death both in vitro and in vivo. Supplementation of ATM-inhibited cells with amino acids, branched-chain amino acids (BCAAs) in particular, abrogated macropinocytosis. Analysis of ATM-inhibited cells in vitro demonstrated increased BCAA uptake, and metabolomics of ascites and interstitial fluid from tumors indicated decreased BCAAs in the microenvironment of ATM-inhibited tumors. These data reveal a novel basis of ATM-mediated tumor suppression whereby loss of ATM stimulates protumorigenic uptake of nutrients in part via macropinocytosis to promote cancer cell survival and reveal a potential metabolic vulnerability of ATM-inhibited cells.

Impact of COVID-19 on tuberculosis detection and treatment in Baja California, México.

In 2020, Mexico reported the lowest tuberculosis (TB) incidence on record, and it is unclear to what extent COVID-19 has impacted TB surveillance, diagnosis, and treatment. It is important to understand COVID-19's impact in Baja California (BC), which has the highest TB burden in Mexico. With the increasing number of migrants and asylum seekers arriving in BC, limited resources and crowded living conditions increase the risk of TB transmission. The purpose of this study was to assess the impact of COVID-19 on TB diagnosis and treatment in BC. We were also interested in health disparities experienced by migrants in BC. We conducted a mixed methods analysis using quantitative surveillance data obtained from the Mexico National TB Program (NTP) and qualitative data collected through in-depth interviews and focus group discussions with TB program directors and personnel in BC's four provincial health jurisdictions. Compared to the year prior, surveillance data from March 2020 - February 2021 revealed that TB incidence in BC declined by 30.9% and favorable TB outcomes (TB cure or treatment completion) declined by 49.8%. Elucidating differences by migrant status was complicated by the lack of standardized collection of migrant status by the NTP. Qualitative analysis revealed that TB diagnostic and treatment supplies and services became limited and disproportionately accessible across jurisdictions since the pandemic began; however, favorable adaptations were also reported, such as increased telemedicine use and streamlined care referral processes. Participants shared that migrant status is susceptible to misclassification and that TB care is difficult due to the transitory nature of migrants. This study did not identify major differences in TB service delivery or access between migrants and non-migrants in BC; however, migrant status was frequently missing. COVID-19 has overwhelmed health systems worldwide, disrupting timely TB diagnostic and treatment services, and potentially caused underdiagnosis of TB in BC. TB programs in BC should quickly restore essential services that were disrupted by COVID-19 while identifying and preserving beneficial program adaptations, such as telemedicine and streamlined care referral processes. Improved methods for documenting migrant status of TB cases are also needed.

The impact of the COVID-19 pandemic among migrants in shelters in Tijuana, Baja California, Mexico.

INTRODUCTION: Migrants, especially those in temporary accommodations like camps and shelters, might be a vulnerable population during the COVID-19 pandemic, but little is known about the impact of the pandemic in these settings in low-income and middle-income countries. We assessed SARS-CoV-2 seropositivity and RNA prevalence, the correlates of seropositivity (emphasising socially determined conditions), and the socioeconomic impacts of the pandemic among migrants living in shelters in Tijuana, a city on the Mexico-US border. METHODS: We conducted a cross-sectional, non-probability survey of migrants living in shelters in Tijuana in November-December 2020 and February-April 2021. Participants completed a questionnaire and provided anterior nasal swab and blood samples for detection of SARS-CoV-2 RNA and antibodies (IgG and IgM), respectively. We explored whether SARS-CoV-2 infection was associated with sociodemographic and migration-related variables, access to sanitation, protective behaviours and health-related factors. RESULTS: Overall, 481 participants were enrolled, 67.7% from Northern Central America, 55.3% women, mean age 33.2 years. Seven (1.5%) participants had nasal swabs positive for SARS-CoV-2 RNA and 53.0% were SARS-CoV-2 seropositive. Avoiding public transportation (OR 0.59, 95% CI 0.39 to 0.90) and months living in Tijuana (OR 1.06, 95% CI 1.02 to 1.10) were associated with seropositivity. Sleeping on the streets or other risky places and having diabetes were marginally associated with seropositivity. Most participants (90.2%) had experienced some socioeconomic impact of the pandemic (eg, diminished income, job loss). CONCLUSION: Compared with results from other studies conducted in the general population in Mexico at a similar time, migrants living in shelters were at increased risk of acquiring SARS-CoV-2, and they suffered considerable adverse socioeconomic impacts as a consequence of the pandemic. Expanded public health and other social support systems are needed to protect migrants from COVID-19 and reduce health inequities.

Apicomplexans in small mammals from Chile, with the first report of the Babesia microti group in South American rodents.

Small mammals play an essential role as disseminators of pathogens because they reach high population densities and have ubiquitous distributions. In the Northern Hemisphere rodents are well recognized as reservoirs for tick-borne bacteria of the Anaplasmataceae family and also apicomplexan protozoans. In contrast, South American rodents hosting these microorganisms have been rarely identified. In this study, we collected blood from rodents and marsupials in northern Chile and screened for Anaplasmataceae bacteria and apicomplexan protozoa. Overall, 14.7% of the samples were positive for Babesia, Hepatozoon, and Sarcocystidae using conventional PCR assays targeting the structural 18S rRNA locus (18S). Phylogenetic analyses performed with amplicons derived from 18S and cytochrome c oxidase (COI) gene provided evidence of a Babesia sp. belonging to the Babesia microti group in Phyllotis darwini, and a novel Babesia genotype in P. darwini and Abrothrix jelskii. Furthermore, four novel genotypes of Hepatozoon retrieved from Abrothrix olivacea, P. darwini, and Oligoryzomys longicaudatus, formed independent lineages within a clade that includes additional Hepatozoon spp. detected in South American rodents. Moreover, an incidental finding of a previously detected apicomplexan, herein designated as Sarcocystidae sp., was recorded in Thylamys opossums with a high prevalence, indicating a possible specific association with these mammals. Phylogenetic analysis of Sarcoystidae sp. clearly demonstrated its relatedness to apicomplexans detected in Australian marsupials. Our results expand the range of mammals hosting tick-borne apicomplexans in South America, highlight a novel clade consisting of South American babesias, and report for the first time the B. microti group infecting rodents in the region.

Prevalence of SARS-CoV-2 infection in Baja California, Mexico: Findings from a community-based survey in February 2021 in the Mexico-United States border.

Between March 2020 and February 2021, the state of Baja California, Mexico, which borders the United States, registered 46,118 confirmed cases of COVID-19 with a mortality rate of 238.2 deaths per 100,000 residents. Given limited access to testing, the population prevalence of SARS-CoV-2 infection is unknown. The objective of this study is to estimate the seroprevalence and real time polymerase chain reaction (RT-PCR) prevalence of SARS-CoV-2 infection in the three most populous cities of Baja California prior to scale-up of a national COVID-19 vaccination campaign. Probabilistic three-stage clustered sampling was used to conduct a population-based household survey of residents five years and older in the three cities. RT-PCR testing was performed on nasopharyngeal swabs and SARS-CoV-2 seropositivity was determined by IgG antibody testing using fingerstick blood samples. An interviewer-administered questionnaire assessed participants' knowledge, attitudes, and preventive practices regarding COVID-19. In total, 1,126 individuals (unweighted sample) were surveyed across the three cities. Overall prevalence of SARS-CoV-2 infection by RT-PCR was 7.8% (95% CI 5.5-11.0) and IgG seroprevalence was 21.1% (95% CI 17.4-25.2). There was no association between border crossing in the past 6 months and SARS-CoV-2 prevalence (unadjusted OR 0.40, 95%CI 0.12-1.30). While face mask use and frequent hand washing were common among participants, quarantine or social isolation at home to prevent infection was not. Regarding vaccination willingness, 30.4% (95% CI 24.4-3 7.1) of participants said they were very unlikely to get vaccinated. Given the high prevalence of active SARS-CoV-2 infection in Baja California at the end of the first year of the pandemic, combined with its low seroprevalence and the considerable proportion of vaccine hesitancy, this important area along the Mexico-United States border faces major challenges in terms of health literacy and vaccine uptake, which need to be further explored, along with its implications for border restrictions in future epidemics.

Role of resective surgery in patients older than 60 years with therapy-resistant epilepsy.

OBJECTIVE: Epilepsy surgery for older adults is controversial owing to their longer duration of epilepsy and perceived higher surgical risk. However, because of an aging population and documented benefit of epilepsy surgery, surgery is considered more frequently for these patients. The authors' objective was to analyze the role of resective surgery in patients older than 60 years and to assess outcomes and safety. METHODS: The authors conducted a retrospective analysis of 595 patients who underwent resective epilepsy surgery at their center from 1999 to 2018. Thirty-one patients aged 60 years or older were identified. Sixty patients younger than 60 years were randomly selected as controls. Population characteristics, results of presurgical evaluations, outcomes, and complications were analyzed. RESULTS: No significant differences were found between the groups in terms of hemisphere dominance, side of surgery, presence of a lesion, and incidence of temporal lobe epilepsy. Epilepsy duration was greater in the older cohort (p = 0.019), and invasive EEG was more commonly employed in younger patients (p = 0.030). The rates of Engel class I outcome at 6 months, 1 year, and 2 years were 89.7%, 96.2%, and 94.7% for the older group and 75% (p = 0.159), 67.3% (p = 0.004), and 75.8% (p = 0.130) for the younger group, respectively. The proportion of seizure-free patients was greatest among those with temporal lobe epilepsy, particularly in the older group. Neurological complication rates did not differ significantly between groups, however medical and other minor complications occurred more frequently in the older group. CONCLUSIONS: Patients older than 60 years had equal or better outcomes at 1 year after epilepsy surgery than younger patients. A trend toward a greater proportion of patients with lesional temporal lobe epilepsy was found in the older group. These results suggest that good seizure outcomes can be obtained in older patients despite longer duration of epilepsy.