The crucial role of diverse animal models to investigate cochlear aging and hearing loss.

Age-related hearing loss affects a large and growing segment of the population, with profound impacts on quality of life. Age-related pathology of the cochlea-the mammalian hearing organ-underlies age-related hearing loss. Because investigating age-related changes in the cochlea in humans is challenging and often impossible, animal models are indispensable to investigate these mechanisms as well as the complex consequences of age-related hearing loss on the brain and behavior. In this review, we advocate for a comparative and interdisciplinary approach while also addressing the challenges of comparing age-related hearing loss across species with varying lifespans. We describe the experimental advantages and limitations as well as areas for future research in well-established models of age-related hearing loss, including mice, rats, gerbils, chinchillas, and birds. We also indicate the need to expand characterization of age-related hearing loss in other established animal models, especially guinea pigs, cats, and non-human primates, in which auditory function is well characterized but age-related cochlear pathology is understudied. Finally, we highlight the potential of emerging animal models for advancing our understanding of age-related hearing loss, including deer mice, with their notably extended lifespans and preserved hearing, naked mole rats, with their exceptional longevity and extensive vocal communications, as well as zebrafish, which offer genetic tractability and suitability for drug screening. Ultimately, a comparative and interdisciplinary approach in auditory research, combining insights from various animal models with human studies, is key to robust and reliable research outcomes that better advance our understanding and treatment of age-related hearing loss.

Promoting diverse perspectives: Addressing health disparities related to Alzheimer's and all dementias.

Dementia research lacks appropriate representation of diverse groups who often face substantial adversity and greater risk of dementia. Current research participants are primarily well-resourced, non-Hispanic White, cisgender adults who live close to academic medical centers where much of the research is based. Consequently, the field faces a knowledge gap about Alzheimer's-related risk factors in those other groups. The Alzheimer's Association hosted a virtual conference on June 14-16, 2021, supported in part by the National Institute on Aging (R13 AG072859-01), focused on health disparities. The conference was held entirely online and consisted of 2 days of core programming and a day of focused meetings centered on American Indian and Alaska Natives and on LGBTQIA+ populations. Over 1300 registrants attended discussions focused on the structural and systemic inequities experienced across diverse groups, as well as ways to investigate and address these inequities.

Systematic computer-aided disulfide design as a general strategy to stabilize prefusion class I fusion proteins.

Numerous enveloped viruses, such as coronaviruses, influenza, and respiratory syncytial virus (RSV), utilize class I fusion proteins for cell entry. During this process, the proteins transition from a prefusion to a postfusion state, undergoing substantial and irreversible conformational changes. The prefusion conformation has repeatedly shown significant potential in vaccine development. However, the instability of this state poses challenges for its practical application in vaccines. While non-native disulfides have been effective in maintaining the prefusion structure, identifying stabilizing disulfide bonds remains an intricated task. Here, we present a general computational approach to systematically identify prefusion-stabilizing disulfides. Our method assesses the geometric constraints of disulfide bonds and introduces a ranking system to estimate their potential in stabilizing the prefusion conformation. We found, for the RSV F protein, that disulfides restricting the initial stages of the conformational switch can offer higher stability to the prefusion state than those preventing unfolding at a later stage. The implementation of our algorithm on the RSV F protein led to the discovery of prefusion-stabilizing disulfides, providing evidence that supports our hypothesis. Furthermore, the evaluation of our top design as a vaccine candidate in a cotton rat model demonstrated robust protection against RSV infection, highlighting the potential of our approach for vaccine development.

A general computational design strategy for stabilizing viral class I fusion proteins.

Many pathogenic viruses rely on class I fusion proteins to fuse their viral membrane with the host cell membrane. To drive the fusion process, class I fusion proteins undergo an irreversible conformational change from a metastable prefusion state to an energetically more stable postfusion state. Mounting evidence underscores that antibodies targeting the prefusion conformation are the most potent, making it a compelling vaccine candidate. Here, we establish a computational design protocol that stabilizes the prefusion state while destabilizing the postfusion conformation. With this protocol, we stabilize the fusion proteins of the RSV, hMPV, and SARS-CoV-2 viruses, testing fewer than a handful of designs. The solved structures of these designed proteins from all three viruses evidence the atomic accuracy of our approach. Furthermore, the humoral response of the redesigned RSV F protein compares to that of the recently approved vaccine in a mouse model. While the parallel design of two conformations allows the identification of energetically sub-optimal positions for one conformation, our protocol also reveals diverse molecular strategies for stabilization. Given the clinical significance of viruses using class I fusion proteins, our algorithm can substantially contribute to vaccine development by reducing the time and resources needed to optimize these immunogens.

Mental Well-being InSciEd Out: Health Partnerships with the Boys & Girls Clubs of Puerto Rico.

BACKGROUND: Mental health care is a top clinical concern for modern Puerto Rico, especially given a dramatically changing economic landscape paired with recurrent natural disasters. Youth are particularly at-risk due to long-term impacts of toxic stress and adverse childhood experiences on health and development. OBJECTIVES: Here we present a novel clinician-community-educator-scientist partnership to address Puerto Rican youth mental well-being and wellness. We deployed pilot health workshops within the Boys & Girls Clubs of Puerto Rico to build youth mental health conceptual understanding and competencies in stress recognition and management. The work in progress herein evaluates acceptability and feasibility of our curricular model. METHODS: Dialogue with community stakeholders guided curricular design of workshops for youth ages 6 to 13 and older. Prior to implementation, educators and volunteers attended a 1-day training on educational strategies. Workshop success was evaluated using qualitative approaches (i.e., narrative feedback, educator and volunteer reflections, youth Talking Drawings) to assess youth engagement, youth conceptual health understanding, and educator/volunteer impressions of feasibility and impact. RESULTS: Initial findings indicate high acceptability and feasibility of our curricular model. Youth engagement and enthusiasm were noted in educator feedback and continue to be sustained post-workshop. Preliminary analysis shows accompanying increases in youth conceptual mental health understanding, particularly for 6- to 12-year-olds in recognition of stress and healthy coping mechanisms. Reciprocal gains were observed for volunteers. CONCLUSIONS: Activities have evolved into a formal partnership called Semilla, which features expanded analysis of mental well-being and wellness outcomes. Our collaborative model continues to engage Puerto Rican youth in the science of their well-being.

Perinatal Mental Health Outcomes Following Natural Disasters.

This Viewpoint discusses mental health outcomes associated with natural disaster­related stressors during the perinatal period.

Mental health impact of the COVID-19 pandemic in perinatal women living in Puerto Rico.

BACKGROUND: Studies have reported an increase in mental health disorders during the perinatal period as a result of the COVID-19 pandemic and the quarantine restrictions imposed. The effects of untreated maternal mental health have an adverse impact on the mother, the development of the baby, and the family system. Determinants of health, recent natural disasters, and disparities in perinatal care that impact perinatal women in Puerto Rico place them at a higher risk of mental health difficulties. AIM: It is therefore, of extreme importance, to evaluate the effect that the COVID-19 pandemic has had on this vulnerable population. DESIGN: This is a cross-sectional observational study that interviewed 100 women in the perinatal period during the COVID-19 lockdown measures in Puerto Rico. Participants completed the Spanish version of the COVID-19 Perinatal Experiences (COPE-IS) questionnaire and assessments of clinical depression (PHQ-9) and anxiety (GAD-7). RESULTS: The prevalence of moderate to severe risk of depression in this sample is 14%, while 17% showed clinical signs of anxiety. Concerns about social impact and the quarantine mandate were the most common stressors reported. Additionally, our sample reported concerns about the impact the pandemic would have on future employment and finances. CONCLUSION: Perinatal women showed significantly higher prevalence of depression and anxiety during the COVID -19 pandemic when compared to the mental health prevalence of the general population pre-pandemic in Puerto Rico. The concerns identified during the pandemic provide information on the importance of a biopsychosocial approach to perinatal mental health care.

Platinum and palladium nanoparticles on boron-doped diamond for the electrochemical detection of hydrogen peroxide: a comparison study.

Hydrogen peroxide (H2O2) plays a role in many facets - a household item, an important industrial chemical, a biomarker in vivo, and several others. For this reason, its measurement and quantification in a variety of media are important. While spectroscopic detection is primarily used for H2O2, electrochemical methods offer advantages in versatility, cost, and sensitivity. In this work, we investigate a 2-step surface metal nanoparticle (NP) modification for platinum (Pt) and palladium (Pd) on boron-doped diamond (BDD) electrodes for the detection of H2O2. Several parameters such as the metal salt concentration and electrodeposition charge in the 2-step modification were varied to find an optimum. Using cyclic voltammetry (CV), the BDD-PdNP electrode types were found to yield a sharper, more well-resolved H2O2 oxidation peak compared to the BDD-PtNP electrodes. Both metal NP electrode types significantly improved the response compared to the bare BDD electrode; a 150-200× improvement in sensitivity was observed across all modified electrode types. Calibration experiments were completed at both low and high concentration ranges in stagnant and flow-based solutions. The lowest limit of detection (LOD) obtained was 50 nM (5E-08 M) on a BDD-PdNP electrode modified with 1.0 mM PdCl2 to 5.0 mC in the wet chemical seeding and electrodeposition steps. 0.25 mM PdCl2 to 3.23 mC and 0.25 mM HPtCl6- to 3.23 mC also yielded a sufficient response for low-level H2O2, with LODs around 100 nM (1E-07 M). Overall, this work exemplifies the wide applicability of BDD and achieves sub-µM H2O2 LODs with a non-enzymatic electrode material.

Cross-Species Convergence of Brain Transcriptomic and Epigenomic Findings in Posttraumatic Stress Disorder: A Systematic Review.

Introduction: Posttraumatic stress disorder (PTSD) is a complex multifactorial disorder influenced by the interaction of genetic and environmental factors. Analyses of epigenomic and transcriptomic modifications may help to dissect the biological factors underlying the gene-environment interplay in PTSD. To date, most human PTSD epigenetics studies have used peripheral tissue, and these findings have complex and poorly understood relationships to brain alterations. Studies examining brain tissue may help characterize the brain-specific transcriptomic and epigenomic profiles of PTSD. In this review, we compiled and integrated brain-specific molecular findings of PTSD from humans and animals. Methods: A systematic literature search according to the PRISMA criteria was performed to identify transcriptomic and epigenomic studies of PTSD, focusing on brain tissue from human postmortem samples or animal-stress paradigms. Results: Gene- and pathway-level convergence analyses revealed PTSD-dysregulated genes and biological pathways across brain regions and species. A total of 243 genes converged across species, with 17 of them significantly enriched for PTSD. Chemical synaptic transmission and signaling by G-protein-coupled receptors were consistently enriched across omics and species. Discussion: Our findings point out dysregulated genes highly replicated across PTSD studies in humans and animal models and suggest a potential role for the corticotropin-releasing hormone/orexin pathway in PTSD's pathophysiology. Further, we highlight current knowledge gaps and limitations and recommend future directions to address them.

Dedifferentiation and Proliferation of Artery Endothelial Cells Drive Coronary Collateral Development in Mice.

BACKGROUND: Collateral arteries act as natural bypasses which reroute blood flow to ischemic regions and facilitate tissue regeneration. In an injured heart, neonatal artery endothelial cells orchestrate a systematic series of cellular events, which includes their outward migration, proliferation, and coalescence into fully functional collateral arteries. This process, called artery reassembly, aids complete cardiac regeneration in neonatal hearts but is absent in adults. The reason for this age-dependent disparity in artery cell response is completely unknown. In this study, we investigated if regenerative potential of coronary arteries is dictated by their ability to dedifferentiate. METHODS: Single-cell RNA sequencing of coronary endothelial cells was performed to identify differences in molecular profiles of neonatal and adult endothelial cells in mice. Findings from this in silico analyses were confirmed with in vivo experiments using genetic lineage tracing, whole organ immunostaining, confocal imaging, and cardiac functional assays in mice. RESULTS: Upon coronary occlusion, neonates showed a significant increase in actively cycling artery cells and expressed prominent dedifferentiation markers. Data from in silico pathway analyses and in vivo experiments suggested that upon myocardial infarction, cell cycle reentry of preexisting neonatal artery cells, the subsequent collateral artery formation, and recovery of cardiac function are dependent on arterial VegfR2 (vascular endothelial growth factor receptor-2). This subpopulation of dedifferentiated and proliferating artery cells was absent in nonregenerative postnatal day 7 or adult hearts. CONCLUSIONS: These data indicate that adult artery endothelial cells fail to drive collateral artery development due to their limited ability to dedifferentiate and proliferate.

Exploring the antibacterial potential of venoms from Argentinian animals.

The resistance to antimicrobials developed by several bacterial species has become one of the main health problems in recent decades. It has been widely reported that natural products are important sources of antimicrobial compounds. Considering that animal venoms are under-explored in this line of research, in this study, we screened the antibacterial activity of venoms of eight snake and five lepidopteran species from northeastern Argentina. Twofold serial dilutions of venoms were tested by the agar well-diffusion method and the minimum inhibitory concentration (MIC) determination against seven bacterial strains. We studied the comparative protein profile of the venoms showing antibacterial activity. Only the viperid and elapid venoms showed remarkable dose-dependent antibacterial activity towards most of the strains tested. Bothrops diporus venom showed the lowest MIC values against all the strains, and S. aureus ATCC 25923 was the most sensitive strain for all the active venoms. Micrurus baliocoryphus venom was unable to inhibit the growth of Enterococcus faecalis. Neither colubrid snake nor lepidopteran venoms exhibited activity on any bacterial strain tested. The snake venoms exhibiting antibacterial activity showed distinctive protein profiles by SDS-PAGE, highlighting that we could reveal for the first time the main protein families which may be thought to contribute to the antibacterial activity of M. baliocoryphus venom. This study paves the way to search for new antibacterial agents from Argentinian snake venoms, which may be a further opportunity to give an added value to the local biodiversity.

A general computational design strategy for stabilizing viral class I fusion proteins.

Many pathogenic viruses, including influenza virus, Ebola virus, coronaviruses, and Pneumoviruses, rely on class I fusion proteins to fuse viral and cellular membranes. To drive the fusion process, class I fusion proteins undergo an irreversible conformational change from a metastable prefusion state to an energetically more favorable and stable postfusion state. An increasing amount of evidence exists highlighting that antibodies targeting the prefusion conformation are the most potent. However, many mutations have to be evaluated before identifying prefusion-stabilizing substitutions. We therefore established a computational design protocol that stabilizes the prefusion state while destabilizing the postfusion conformation. As a proof of concept, we applied this principle to the fusion protein of the RSV, hMPV, and SARS-CoV-2 viruses. For each protein, we tested less than a handful of designs to identify stable versions. Solved structures of designed proteins from the three different viruses evidenced the atomic accuracy of our approach. Furthermore, the immunological response of the RSV F design compared to a current clinical candidate in a mouse model. While the parallel design of two conformations allows identifying and selectively modifying energetically less optimized positions for one conformation, our protocol also reveals diverse molecular strategies for stabilization. We recaptured many approaches previously introduced manually for the stabilization of viral surface proteins, such as cavity-filling, optimization of polar interactions, as well as postfusion-disruptive strategies. Using our approach, it is possible to focus on the most impacting mutations and potentially preserve the immunogen as closely as possible to its native version. The latter is important as sequence re-design can cause perturbations to B and T cell epitopes. Given the clinical significance of viruses using class I fusion proteins, our algorithm can substantially contribute to vaccine development by reducing the time and resources needed to optimize these immunogens.

Pre- and peri-natal hurricane exposure alters DNA methylation patterns in children.

Hurricane Maria was the worst recorded natural disaster to affect Puerto Rico. Increased stress in pregnant women during and in the aftermath of the hurricane may have induced epigenetic changes in their infants, which could affect gene expression. Stage of gestation at the time of the event was associated with significant differences in DNA methylation in the infants, especially those who were at around 20-25 weeks of gestation when the hurricane struck. Significant differences in DNA methylation were also associated with maternal mental status assessed after the hurricane, and with property damage. Hurricane Maria could have long lasting consequences to children who were exposed to this disaster during pregnancy.

The psychological impact of the COVID-19 pandemic on physicians in Puerto Rico: a cross-sectional study after the second wave in 2021.

Introduction: Health care providers faced a challenge with the emergence of COVID-19 and its rapid spread. Early studies measuring the psychological impact of COVID-19 on the general population found high levels of anxiety and sleep disorders. The primary goal of this project was to assess the psychological impact of COVID-19 on physicians in Puerto Rico. Materials and methods: A cross-sectional study of physicians in Puerto Rico was conducted anonymously and electronically from February 2021 through April 2021. The electronic survey included socio-demographic data and 4 self-administered assessment tools (Generalized Anxiety Disorder-7, Perceived Stress Scale-10, Pittsburgh Sleep Quality Index and COVID-19 Organizational Support) for anxiety, perceived stress, sleep disturbances, and organizational support during the COVID-19 pandemic. Results: A total of 145 physicians completed the survey, with a female predominance of 53.5% and a majority practicing in the San Juan metropolitan area (50.3%). Mild anxiety symptoms were reported in 26.9% of physicians, and 33.8% had moderate to severe anxiety symptoms. Moderate to high perceived stress was found in 69.9% of participants, and women reported statistically significantly higher levels of anxiety symptoms (8.84 ± 5.99; p = 0.037) and stress (19.0 ± 6.94, p = 0.001). The Pittsburgh Sleep Quality Index reported 67.9% of physicians with global scores associated with poor sleep quality. Assessment of perceived organizational support found a high perception of work support (65.7%) but low perception of personal support (43.4%) and risk support (30.3%). A correlation analysis found a negative correlation for work and personal support, but a positive correlation for risk support, all statistically significant. Conclusion: COVID-19 had a lasting psychological impact in health care providers in Puerto Rico a year after the beginning of the pandemic. Our data supports the importance of organizational support and its correlation with the development of anxiety. It is thus essential to develop strategies to identify individuals at risk of experiencing psychological disturbances and to provide effective support for medical professionals during medical emergencies for their well-being and optimal delivery of patient care.

Relationship between the Prenatal Diagnosis of Placenta Acreta Spectrum and Lower Use of Blood Components.

OBJECTIVE: To describe the clinical results of patients admitted and managed as cases of placenta accreta spectrum (PAS) at a Central American public hospital and the influence of the prenatal diagnosis on the condition. MATERIALS AND METHODS: A retrospective analysis of PAS patients treated at Hospital Bertha Calderón Roque, in Managua, Nicaragua, between June 2017 and September 2021. The diagnostic criteria used were those of the International Federation of Gynecology and Obstetrics (Fédération Internationale de Gynécologie et d'Obstétrique, FIGO, in French). The population was divided into patients with a prenatal ultrasonographic diagnosis of PAS (group 1) and those whose the diagnosis of PAS was established at the time of the caesarean section (group 2). RESULTS: During the search, we found 103 cases with a histological and/or clinical diagnosis of PAS; groups 1 and 2 were composed of 51 and 52 patients respectively. Regarding the clinical results of both groups, the patients in group 1 presented a lower frequency of transfusions (56.9% versus 96.1% in group 2), use of a lower number of red blood cell units (RBCUs) among those undergoing transfusions (median: 1; interquartile range: [IQR]: 0-4 versus median: 3; [IQR]: 2-4] in group 2), and lower frequency of 4 or more RBCU transfusions (29.4% versus 46.1% in group 2). Group 1 also exhibited a non-significant trend toward a lower volume of blood loss (1,000 mL [IQR]: 750-2,000 mL versus 1,500 mL [IQR]: 1,200-1,800 mL in group 2), and lower requirement of pelvic packing (1.9% versus 7.7% in group 2). CONCLUSION: Establishing a prenatal diagnosis of PAS is related to a lower frequency of transfusions. We observed a high frequency of prenatal diagnostic failures of PAS. It is a priority to improve prenatal detection of this disease.

Relationship between the Prenatal Diagnosis of Placenta Acreta Spectrum and Lower Use of Blood Components / Relação entre o diagnóstico prenatal de espectro da placenta acreta e menor uso de hemoderivados

Abstract Objective To describe the clinical results of patients admitted and managed as cases of placenta accreta spectrum (PAS) at a Central American public hospital and the influence of the prenatal diagnosis on the condition. Materials and Methods A retrospective analysis of PAS patients treated at Hospital Bertha Calderón Roque, in Managua, Nicaragua, between June 2017 and September 2021. The diagnostic criteria used were those of the International Federation of Gynecology and Obstetrics (Fédération Internationale de Gynécologie et d'Obstétrique, FIGO, in French). The population was divided into patients with a prenatal ultrasonographic diagnosis of PAS (group 1) and those whose the diagnosis of PAS was established at the time of the caesarean section (group 2). Results During the search, we found 103 cases with a histological and/or clinical diagnosis of PAS; groups 1 and 2 were composed of 51 and 52 patients respectively. Regarding the clinical results of both groups, the patients in group 1 presented a lower frequency of transfusions (56.9% versus 96.1% in group 2), use of a lower number of red blood cell units (RBCUs) among those undergoing transfusions (median: 1; interquartile range: [IQR]: 0-4 versus median: 3; [IQR]: 2-4] in group 2), and lower frequency of 4 or more RBCU transfusions (29.4% versus 46.1% in group 2). Group 1 also exhibited a non-significant trend toward a lower volume of blood loss (1,000 mL [IQR]: 750-2,000 mL versus 1,500 mL [IQR]: 1,200-1,800 mL in group 2), and lower requirement of pelvic packing (1.9% versus 7.7% in group 2). Conclusion Establishing a prenatal diagnosis of PAS is related to a lower frequency of transfusions. We observed a high frequency of prenatal diagnostic failures of PAS. It is a priority to improve prenatal detection of this disease.

Unraveling the distinctive venomous features of the saturniid Hylesia sp.: An integrative approach of a public health concern in Argentina.

The saturniid genus Hylesia is well known for the cutaneous lepidopterism induced by airborne setae on contact with the skin. Although several cases of such dermatitis have been reported in Argentina, no information about their venoms and toxicological implications on human health is available yet. Thus, we conducted a morphological analysis of the setae/spines and a toxinological characterization (through biological assays and proteomic techniques) of the bristle extract from caterpillars and moths of Hylesia sp. from Misiones, Argentina. By scanning electron microscopy, we revealed the various and distinctive types of urticating structures: harpoon-shaped or spiny setae in caterpillars, and setae with barb-like structures in female moths. Their venom electrophoretic profiles were substantially different, presenting proteins related to toxicity, such as serpins and serine peptidases. The female moth venom exhibited higher caseinolytic activity than the caterpillar venom, and coincidentally only the former noticeably hydrolyzed fibrinogen and gelatin. In addition, the female venom displayed a dose-dependent procoagulant effect. The injection of this venom into mouse skin led to the rapid detection of an increased number of intact and degranulated mast cells in the dermis; a few areas of focal subcutaneous hemorrhage were also observed after 5 h of injection. Altogether, this study provides relevant information about the pathophysiological mechanisms whereby Hylesia sp. from northeastern Argentina can induce toxicity on human beings, and paves the way for treatment strategies of accidents caused by this saturniid lepidopteran.

Design and Study of a Photo-Switchable Polymeric System in the Presence of ZnS Nanoparticles under the Influence of UV Light Irradiation.

Recent progress in the field of photosensitive materials has prompted a need to develop efficient methods to synthesize materials with basic intermolecular architectural designs and novel properties. Accordingly, in this work we design and study a photoactive polymer as a photo-switchable polymeric system in the presence and absence of ZnS nanoparticles (average size < 10 nm) at 5 wt.%. The influence of UV light irradiation on its properties were also studied. The photoactive block copolymer was obtained from styrene (S) and methyl methacrylate (MMA) as monomers and 1-(2-hydroxyethyl)-3,3-dimethylindoline-6-nitrobenzopyran (SP) was grafted to the block copolymer backbone as a photochromic agent. Furthermore, the incorporation of ZnS (NPs) as photo-optical switch component into the system enhances the purple colored photo-emission, with the open form of the spiropyran derivative (merocyanine, MC). The ZnS stabilize the isomeric equilibrium in the MC interconversion of the photochromic agent. The photo-switchable properties of the PS-b-PMMA-SP in the presence of ZnS (NPs) were examined using UV-VIS spectroscopy, Photoluminescence (PL) spectroscopy, optical fluorescence and scanning electronic microscopy (SEM-EDX.). The observed changes in the absorbance, fluorescence and morphology of the system were associated to the reversible interconversion of the two states of the photochromic agent which regulates the radiative deactivation of the luminescent ZnS NPs component. After UV irradiation the photoactive polymer becomes purple in color. Therefore, these basic studies can lead to the development of innovative functional and nanostructured materials with photosensitive character as photosensitive molecular switches.

Decreased vaccine protection of egg-based influenza vaccine in the elderly and nonhemagglutinin-focused immunity.

Severe influenza illness or death is a serious concern among the elderly population despite vaccination. To investigate how the adaptive immune response after vaccination varies with the patient's age, Jung et al., in a recent issue of the JCI, extensively analyzed the serum antibody response in different age groups after immunization with the egg-based influenza vaccine Fluzone. As expected, the immune response in young adults was dominated by antibodies targeting the influenza hemagglutinin (HA) protein. On the contrary, the serological repertoire of elderly donors was characterized by cross-reactive (CR) antibodies recognizing non-HA antigens. Surprisingly, a substantial fraction of these CR antibodies targeted sulfated glycans typical of egg-produced proteins, which does not provide protection against human influenza viruses. Overall, these findings are of great value in understanding suboptimal immunity after influenza vaccination and shaping future vaccine efforts that will achieve increased protection in the elderly.

Whole Genome Sequencing Links Mycobacterium bovis From Cattle, Cheese and Humans in Baja California, Mexico.

Mycobacterium bovis causes tuberculosis (TB) in cattle, which in turn can transmit the pathogen to humans. Tuberculosis in dairy cattle is of particular concern where the consumption of raw milk and dairy products is customary. Baja California (BCA), Mexico, presents high prevalence of TB in both cattle and humans, making it important to investigate the molecular epidemiology of the disease in the region. A long-term study was undertaken to fully characterize the diversity of M. bovis genotypes circulating in dairy cattle, cheese and humans in BCA by whole-genome sequencing (WGS). During a 2-year period, 412 granulomatous tissue samples were collected from local abattoirs and 314 cheese samples were purchased from local stores and vendors in BCA and sent to the laboratory for mycobacterial culture, histology, direct PCR and WGS. For tissue samples M. bovis was recovered from 86.8%, direct PCR detected 90% and histology confirmed 85.9% as mycobacteriosis-compatible. For cheese, M. bovis was recovered from 2.5% and direct PCR detected 6% of the samples. There was good agreement between diagnostic tests. Subsequently, a total of 345 whole-genome SNP sequences were obtained. Phylogenetic analysis grouped these isolates into 10 major clades. SNP analysis revealed putative transmission clusters where the pairwise SNP distance between isolates from different dairies was ≤3 SNP. Also, human and/or cheese isolates were within 8.45 (range 0-17) and 5.8 SNP (range 0-15), respectively, from cattle isolates. Finally, a comparison between the genotypes obtained in this study and those reported previously suggests that the genetic diversity of M. bovis in BCA is well-characterized, and can be used to determine if BCA is the likely source of M. bovis in humans and cattle in routine epidemiologic investigations and future studies. In conclusion, WGS provided evidence of ongoing local transmission of M. bovis among the dairies in this high-TB burden region of BCA, as well as show close relationships between isolates recovered from humans, cheese, and cattle. This confirms the need for a coordinated One Health approach in addressing the elimination of TB in animals and humans. Overall, the study contributes to the knowledge of the molecular epidemiology of M. bovis in BCA, providing insight into the pathogen's dynamics in a high prevalence setting.