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Antimicrobial resistance (AMR), the ability of bacterial species to develop resistance against exposed antibiotics, has gained immense global attention in the past few years. Bacterial infections are serious health concerns affecting millions of people annually worldwide. Therefore, developing novel antibacterial agents that are highly effective and avoid resistance development is imperative. Among various strategies, recent developments in nanozyme technology have shown promising results as antibacterials in several antibiotic-sensitive and resistant bacterial species. Nanozymes offer several advantages over corresponding natural enzymes, such as inexpensive, stable, multifunctional, tunable catalytic properties. Although the use of nanozymes as antibacterial agents has provided promising results, the specific biomolecule-conjugated nanozymes have shown further improvement in catalytic performance and associated antibacterial efficacy. The exclusive design of functional nanozymes with theranostic potential is found to simultaneously inhibit the growth and image of AMR bacterial species. This review comprehensively summarizes the history of nanozymes, their classification, biomolecules conjugated nanozyme, and their mechanism of enzyme-mimetic activity and associated antibacterial activity in antibiotic-sensitive and resistant species. The future needs to effectively engineer the existing or new nanozymes to curb AMR have also been discussed.
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Background: The occurrence of post-traumatic stress disorder (PTSD) following a traumatic event is associated with biological differences that can represent the susceptibility to PTSD, the impact of trauma, or the sequelae of PTSD itself. These effects include differences in DNA methylation (DNAm), an important form of epigenetic gene regulation, at multiple CpG loci across the genome. Moreover, these effects can be shared or specific to both central and peripheral tissues. Here, we aim to identify blood DNAm differences associated with PTSD and characterize the underlying biological mechanisms by examining the extent to which they mirror associations across multiple brain regions. Methods: As the Psychiatric Genomics Consortium (PGC) PTSD Epigenetics Workgroup, we conducted the largest cross-sectional meta-analysis of epigenome-wide association studies (EWASs) of PTSD to date, involving 5077 participants (2156 PTSD cases and 2921 trauma-exposed controls) from 23 civilian and military studies. PTSD diagnosis assessments were harmonized following the standardized guidelines established by the PGC-PTSD Workgroup. DNAm was assayed from blood using either Illumina HumanMethylation450 or MethylationEPIC (850K) BeadChips. A common QC pipeline was applied. Within each cohort, DNA methylation was regressed on PTSD, sex (if applicable), age, blood cell proportions, and ancestry. An inverse variance-weighted meta-analysis was performed. We conducted replication analyses in tissue from multiple brain regions, neuronal nuclei, and a cellular model of prolonged stress. Results: We identified 11 CpG sites associated with PTSD in the overall meta-analysis (1.44e-09 < p < 5.30e-08), as well as 14 associated in analyses of specific strata (military vs civilian cohort, sex, and ancestry), including CpGs in AHRR and CDC42BPB. Many of these loci exhibit blood-brain correlation in methylation levels and cross-tissue associations with PTSD in multiple brain regions. Methylation at most CpGs correlated with their annotated gene expression levels. Conclusions: This study identifies 11 PTSD-associated CpGs, also leverages data from postmortem brain samples, GWAS, and genome-wide expression data to interpret the biology underlying these associations and prioritize genes whose regulation differs in those with PTSD.
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Background: Novel applications of telemedicine can improve care quality and patient outcomes. Telemedicine for intraoperative decision support has not been rigorously studied. Methods: This single centre randomised clinical trial ( clinicaltrials.gov NCT03923699 ) of unselected adult surgical patients was conducted between July 1, 2019 and January 31, 2023. Patients received usual care or decision support from a telemedicine service, the Anesthesiology Control Tower (ACT). The ACT provided real-time recommendations to intraoperative anaesthesia clinicians based on case reviews, machine-learning forecasting, and physiologic alerts. ORs were randomised 1:1. Co-primary outcomes of 30-day all-cause mortality, respiratory failure, acute kidney injury (AKI), and delirium were analysed as intention-to-treat. Results: The trial completed planned enrolment with 71927 surgeries (35956 ACT; 35971 usual care). After multiple testing correction, there was no significant effect of the ACT vs. usual care on 30-day mortality [641/35956 (1.8%) vs 638/35971 (1.8%), risk difference 0.0% (95% CI -0.2% to 0.3%), p=0.96], respiratory failure [1089/34613 (3.1%) vs 1112/34619 (3.2%), risk difference -0.1% (95% CI -0.4% to 0.3%), p=0.96], AKI [2357/33897 (7%) vs 2391/33795 (7.1%), risk difference -0.1% (-0.6% to 0.4%), p=0.96], or delirium [1283/3928 (32.7%) vs 1279/3989 (32.1%), risk difference 0.6% (-2.0% to 3.2%), p=0.96]. There were no significant differences in secondary outcomes or in sensitivity analyses. Conclusions: In this large RCT of a novel application of telemedicine-based remote monitoring and decision support using real-time alerts and case reviews, we found no significant differences in postoperative outcomes. Large-scale intraoperative telemedicine is feasible, and we suggest future avenues where it may be impactful.
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OBJECTIVES: Perioperative mental health of older Black surgical patients is associated with poor surgical outcomes; however, evidence-based perioperative interventions are lacking. Our two study objectives included: first, examine factors affecting perioperative care experiences of older Black surgical patients with mental health problems, and second, ascertain design and implementation requirements for a culturally-adapted perioperative mental health intervention. DESIGN SETTING AND PARTICIPANTS: We conducted six focus groups with older Black patients (n = 15; ≥50 years; surgery within the past 5 years and/or interest in mental health research; history of distress, anxiety, or depression coping with surgery/hospitalization/) from a large academic medical center. We engaged study partners, including interventionists and community members, to gather insights on intervention and implementation needs. We followed a hybrid inductive-deductive thematic approach using open coding and the National Institute on Minority Health and Health Disparities Research Framework. RESULTS: Patients reported that their psychological well-being and long-term mental health outcomes were not appropriately considered during perioperative care. Perceived stressors included interpersonal and structural barriers to using mental healthcare services, clinician treatment biases and ageism in care, and lack of healthcare professional connections/resources. Patients utilized various coping strategies, including talk therapy, faith/spirituality, and family and friends. CONCLUSION: This study offers valuable insights into the experiences of older Black surgical patients and the critical elements for developing a personalized perioperative mental health intervention to support their well-being before, during, and after surgery. Our findings demonstrated a need for a patient-centered and culturally adapted intervention targeting the individual/behavioral and interpersonal levels. Informed by the cultural adaptation framework, we propose a multi-component intervention that integrates psychological and pharmacological components.
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Background: Anaesthesiology clinicians can implement risk mitigation strategies if they know which patients are at greatest risk for postoperative complications. Although machine learning models predicting complications exist, their impact on clinician risk assessment is unknown. Methods: This single-centre randomised clinical trial enrolled patients age ≥18 undergoing surgery with anaesthesiology services. Anaesthesiology clinicians providing remote intraoperative telemedicine support reviewed electronic health records with (assisted group) or without (unassisted group) also reviewing machine learning predictions. Clinicians predicted the likelihood of postoperative 30-day all-cause mortality and postoperative acute kidney injury within 7 days. Area under the receiver operating characteristic curve (AUROC) for the clinician predictions was determined. Results: Among 5,071 patient cases reviewed by 89 clinicians, the observed incidence was 2% for postoperative death and 11% for acute kidney injury. Clinician predictions agreed with the models more strongly in the assisted versus unassisted group (weighted kappa 0.75 versus 0.62 for death [difference 0.13, 95%CI 0.10-0.17] and 0.79 versus 0.54 for kidney injury [difference 0.25, 95%CI 0.21-0.29]). Clinicians predicted death with AUROC of 0.793 in the assisted group and 0.780 in the unassisted group (difference 0.013, 95%CI -0.070 to 0.097). Clinicians predicted kidney injury with AUROC of 0.734 in the assisted group and 0.688 in the unassisted group (difference 0.046, 95%CI -0.003 to 0.091). Conclusions: Although there was evidence that the models influenced clinician predictions, clinician performance was not statistically significantly different with and without machine learning assistance. Further work is needed to clarify the role of machine learning in real-time perioperative risk stratification. Trial Registration: ClinicalTrials.gov NCT05042804.
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Arboviruses such as chikungunya, dengue and zika viruses cause debilitating diseases in humans. The principal vector species that transmits these viruses is the Aedes mosquito. Lack of substantial knowledge of the vector species hinders the advancement of strategies for controlling the spread of arboviruses. To supplement our information on mosquitoes' responses to virus infection, we utilized Aedes aegypti-derived Aag2 cells to study changes at the transcriptional level during infection with chikungunya virus (CHIKV). We observed that genes belonging to the redox pathway were significantly differentially regulated. Upon quantifying reactive oxygen species (ROS) in the cells during viral infection, we further discovered that ROS levels are considerably higher during the early hours of infection; however, as the infection progresses, an increase in antioxidant gene expression suppresses the oxidative stress in cells. Our study also suggests that ROS is a critical regulator of viral replication in cells and inhibits intracellular and extracellular viral replication by promoting the Rel2-mediated Imd immune signalling pathway. In conclusion, our study provides evidence for a regulatory role of oxidative stress in infected Aedes-derived cells.
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Aedes , Arbovirus , Fiebre Chikungunya , Infección por el Virus Zika , Virus Zika , Humanos , Animales , Especies Reactivas de Oxígeno , Mosquitos Vectores , Estrés Oxidativo , Inmunidad InnataRESUMEN
BACKGROUND: Chronic migraine, a highly disabling migraine subtype, affects nearly 2% of the general population. Understanding migraine chronification is vital for developing better treatment and prevention strategies. An important factor in the chronification of migraine is the overuse of acute headache medication. However, the mechanisms behind the transformation of episodic migraine to chronic migraine and vice versa have not yet been elucidated. We performed a longitudinal epigenome-wide association study to identify DNA methylation (DNAm) changes associated with treatment response in patients with chronic migraine and medication overuse as part of the Chronification and Reversibility of Migraine clinical trial. Blood was taken from patients with chronic migraine (n = 98) at baseline and after a 12-week medication withdrawal period. Treatment responders, patients with ≥ 50% reduction in monthly headache days (MHD), were compared with non-responders to identify DNAm changes associated with treatment response. Similarly, patients with ≥ 50% versus < 50% reduction in monthly migraine days (MMD) were compared. RESULTS: At the epigenome-wide significant level (p < 9.42 × 10-8), a longitudinal reduction in DNAm at an intronic CpG site (cg14377273) within the HDAC4 gene was associated with MHD response following the withdrawal of acute medication. HDAC4 is highly expressed in the brain, plays a major role in synaptic plasticity, and modulates the expression and release of several neuroinflammation markers which have been implicated in migraine pathophysiology. Investigating whether baseline DNAm associated with treatment response, we identified lower baseline DNAm at a CpG site (cg15205829) within MARK3 that was significantly associated with MMD response at 12 weeks. CONCLUSIONS: Our findings of a longitudinal reduction in HDAC4 DNAm status associated with treatment response and baseline MARK3 DNAm status as an early biomarker for treatment response, provide support for a role of pathways related to chromatin structure and synaptic plasticity in headache chronification and introduce HDAC4 and MARK3 as novel therapeutic targets.
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Cefaleas Secundarias , Trastornos Migrañosos , Humanos , Estudios Longitudinales , Metilación de ADN , Cefaleas Secundarias/tratamiento farmacológico , Cefaleas Secundarias/genética , Trastornos Migrañosos/tratamiento farmacológico , Trastornos Migrañosos/genética , Trastornos Migrañosos/metabolismo , Cefalea , Biomarcadores/metabolismoRESUMEN
Bacterial infections are considered as one of the major health threats to the global population. The advent of bacterial species with antibiotic resistance has attracted significant efforts to develop novel materials and strategies to effectively avoid the resistance with enhanced antibacterial potential. In this work, we have developed oxidase-mimetic cerium oxide nanoparticles (CeO2 NPs), which exhibit nanozyme activity at physiological pH in the presence of adenosine triphosphate (ATP). The oxidase-mimetic activity was confirmed to involve superoxide radicals using p-benzoquinone and dihydroethidium. Using indole propionic acid, ethanol, and terephthalic acid, it was confirmed that the oxidase-mimetic activity of CeO2 NPs with ATP does not involve the formation of hydroxyl radicals. CeO2 NPs with ATP produced a strong antibacterial activity against Staphylococcus aureus and Escherichia coli within 3 - 6 hrs. The bacterial cell morphology analysis suggested that superoxide radicals generated during the oxidase-mimetic activity of CeO2 NPs with ATP cause distortion of paired and tetrad arrangement (Staphylococcus aureus), loss of cytoplasmic content, damage, and pore formation in the cell wall (Escherichia coli) that led to the death of bacteria. Further, the live/dead assay also concludes the time-dependent death of bacterial cells with the highest death in the cell population exposed to CeO2 NPs and ATP. Thus, the antibacterial activity at physiological pH by superoxide radical generating oxidase-mimetic CeO2 NPs could be further extended to other pathogenic bacterial species.
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Cerio , Nanopartículas del Metal , Nanopartículas , Superóxidos , Oxidorreductasas/metabolismo , Adenosina Trifosfato/metabolismo , Nanopartículas/química , Cerio/farmacología , Cerio/química , Escherichia coli/metabolismo , Bacterias/metabolismo , Antibacterianos/química , Concentración de Iones de Hidrógeno , Nanopartículas del Metal/químicaRESUMEN
Importance: Telemedicine for clinical decision support has been adopted in many health care settings, but its utility in improving intraoperative care has not been assessed. Objective: To pilot the implementation of a real-time intraoperative telemedicine decision support program and evaluate whether it reduces postoperative hypothermia and hyperglycemia as well as other quality of care measures. Design, Setting, and Participants: This single-center pilot randomized clinical trial (Anesthesiology Control Tower-Feedback Alerts to Supplement Treatments [ACTFAST-3]) was conducted from April 3, 2017, to June 30, 2019, at a large academic medical center in the US. A total of 26 254 adult surgical patients were randomized to receive either usual intraoperative care (control group; n = 12 980) or usual care augmented by telemedicine decision support (intervention group; n = 13 274). Data were initially analyzed from April 22 to May 19, 2021, with updates in November 2022 and February 2023. Intervention: Patients received either usual care (medical direction from the anesthesia care team) or intraoperative anesthesia care monitored and augmented by decision support from the Anesthesiology Control Tower (ACT), a real-time, live telemedicine intervention. The ACT incorporated remote monitoring of operating rooms by a team of anesthesia clinicians with customized analysis software. The ACT reviewed alerts and electronic health record data to inform recommendations to operating room clinicians. Main Outcomes and Measures: The primary outcomes were avoidance of postoperative hypothermia (defined as the proportion of patients with a final recorded intraoperative core temperature >36 °C) and hyperglycemia (defined as the proportion of patients with diabetes who had a blood glucose level ≤180 mg/dL on arrival to the postanesthesia recovery area). Secondary outcomes included intraoperative hypotension, temperature monitoring, timely antibiotic redosing, intraoperative glucose evaluation and management, neuromuscular blockade documentation, ventilator management, and volatile anesthetic overuse. Results: Among 26 254 participants, 13 393 (51.0%) were female and 20 169 (76.8%) were White, with a median (IQR) age of 60 (47-69) years. There was no treatment effect on avoidance of hyperglycemia (7445 of 8676 patients [85.8%] in the intervention group vs 7559 of 8815 [85.8%] in the control group; rate ratio [RR], 1.00; 95% CI, 0.99-1.01) or hypothermia (7602 of 11 447 patients [66.4%] in the intervention group vs 7783 of 11 672 [66.7.%] in the control group; RR, 1.00; 95% CI, 0.97-1.02). Intraoperative glucose measurement was more common among patients with diabetes in the intervention group (RR, 1.07; 95% CI, 1.01-1.15), but other secondary outcomes were not significantly different. Conclusions and Relevance: In this randomized clinical trial, anesthesia care quality measures did not differ between groups, with high confidence in the findings. These results suggest that the intervention did not affect the targeted care practices. Further streamlining of clinical decision support and workflows may help the intraoperative telemedicine program achieve improvement in targeted clinical measures. Trial Registration: ClinicalTrials.gov Identifier: NCT02830126.
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Hiperglucemia , Hipotermia , Adulto , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Hipotermia/prevención & control , Hiperglucemia/prevención & control , Grupos Control , Centros Médicos Académicos , GlucosaRESUMEN
Child maltreatment is a major risk factor for both depressive and anxiety disorders. However, many children exposed to maltreatment never meet diagnostic threshold for either disorder while experiencing only transitory symptoms post-exposure. Recent research suggests DNA methylation adds predictive value in explaining variation in the onset and course of multiple psychiatric disorders following exposure to child maltreatment. Epigenetic age acceleration (EAA), the biological aging of cells not attributable to chronological aging, is a stress-sensitive biomarker capturing genome-wide variation in DNA methylation with the potential to identify children who have been maltreated at greatest risk for depressive and anxiety disorders. The current study examined two EAA clocks appropriate for the pediatric population, the Horvath and Pediatric Buccal Epigenetic (PedBE) clocks, and their associations with depressive and anxiety symptom severity following child maltreatment. Children (N = 71) 8-15 years of age, all of whom were exposed to substantiated child maltreatment in the 12 months prior to study entry, were enrolled. Risk modeling adjusting for several confounders revealed that EAA estimated via the Horvath clock was significantly associated with more severe depressive and anxiety symptoms. The PedBE clock was not associated with either depressive or anxiety symptom severity. Sensitivity analyses demonstrated that EAA via the Horvath clock robustly predicted depressive and anxiety symptom severity across multiple modeling scenarios. Our findings advance existing research suggesting EAA, as estimated with the Horvath clock, may be a promising biomarker for identifying children at greatest risk for more severe depressive and anxiety symptoms following maltreatment.
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Envejecimiento , Trastornos de Ansiedad , Humanos , Niño , Lactante , Trastornos de Ansiedad/genética , Trastornos de Ansiedad/epidemiología , Envejecimiento/genética , Metilación de ADN , Ansiedad/genética , Epigénesis GenéticaRESUMEN
Poly ADP-ribose polymerases (PARPs) catalyze ADP-ribosylation, a subclass of post-translational modification (PTM). Mono-ADP-ribose (MAR) moieties bind to target molecules such as proteins and nucleic acids, and are added as part of the process which also leads to formation of polymer chains of ADP-ribose. ADP-ribosylation is reversible; its removal is carried out by ribosyl hydrolases such as PARG (poly ADP-ribose glycohydrolase), TARG (terminal ADP-ribose protein glycohydrolase), macrodomain, etc. In this study, the catalytic domain of Aedes aegypti tankyrase was expressed in bacteria and purified. The tankyrase PARP catalytic domain was found to be enzymatically active, as demonstrated by an in vitro poly ADP-ribosylation (PARylation) experiment. Using in vitro ADP-ribosylation assay, we further demonstrate that the chikungunya virus (CHIKV) nsp3 (non-structural protein 3) macrodomain inhibits ADP-ribosylation in a time-dependent way. We have also demonstrated that transfection of the CHIKV nsP3 macrodomain increases the CHIKV viral titer in mosquito cells, suggesting that ADP-ribosylation may play a significant role in viral replication.
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Child maltreatment (CM) encompasses sexual abuse, physical abuse, emotional abuse, neglect, and exposure to domestic and family violence. Epigenetic research investigating CM has focused on differential DNA methylation (DNAm) in genes associated with the stress response, but there has been limited evaluation of the specific effects of subtypes of CM. This systematic review of literature investigating DNAm associated with CM in non-clinical populations aimed to summarise the approaches currently used in research, how the type of maltreatment and age of exposure were encoded via methylation, and which genes have consistently been associated with CM. A total of fifty-four papers were eligible for review, including forty-one candidate gene studies, eight epigenome-wide association studies, and five studies with a mixed design. The ways in which the various forms of CM were conceptualised and measured varied between papers. Future studies would benefit from assessments that employ conceptually robust definitions of CM, and that capture important contextual information such as age of exposure and subtype of CM.
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Maltrato a los Niños , Metilación de ADN , Niño , Humanos , Maltrato a los Niños/psicologíaRESUMEN
To study mental illness and health, in the past researchers have often broken down their complexity into individual subsystems (e.g., genomics, transcriptomics, proteomics, clinical data) and explored the components independently. Technological advancements and decreasing costs of high throughput sequencing has led to an unprecedented increase in data generation. Furthermore, over the years it has become increasingly clear that these subsystems do not act in isolation but instead interact with each other to drive mental illness and health. Consequently, individual subsystems are now analysed jointly to promote a holistic understanding of the underlying biological complexity of health and disease. Complementing the increasing data availability, current research is geared towards developing novel methods that can efficiently combine the information rich multi-omics data to discover biologically meaningful biomarkers for diagnosis, treatment, and prognosis. However, clinical translation of the research is still challenging. In this review, we summarise conventional and state-of-the-art statistical and machine learning approaches for discovery of biomarker, diagnosis, as well as outcome and treatment response prediction through integrating multi-omics and clinical data. In addition, we describe the role of biological model systems and in silico multi-omics model designs in clinical translation of psychiatric research from bench to bedside. Finally, we discuss the current challenges and explore the application of multi-omics integration in future psychiatric research. The review provides a structured overview and latest updates in the field of multi-omics in psychiatry.
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Trastornos Mentales , Multiómica , Humanos , Genómica , Proteómica/métodos , Aprendizaje Automático , Trastornos Mentales/diagnóstico , Trastornos Mentales/genética , Trastornos Mentales/terapiaRESUMEN
Maternal-infant bonding is important for children's positive development. Poor maternal-infant bonding is a risk factor for negative mother and infant outcomes. Although researchers have examined individual predictors of maternal-infant bonding, studies typically do not examine several concurrent and longitudinal predictors within the same model. This study aimed to evaluate the unique and combined predictive power of cross-sectional and longitudinal predictors of maternal-infant bonding. Participants were 372 pregnant women recruited from an Australian hospital. Data were collected from mothers at antenatal appointments (T0), following their child's birth (T1), and at a laboratory assessment when their child was 5-11-months-old (T2). Poorer bonding at T2 was predicted at T0 by younger maternal age, higher education, and higher antenatal depressive symptoms. Poorer bonding at T2 was predicted at T1 by younger maternal age, higher education, and higher postnatal depressive symptoms. Poorer bonding at T2 was predicted at T2 by younger maternal age, higher education, higher postnatal depression symptoms, higher concurrent perceived social support, and more difficult infant temperament, when controlling for child age at T2. To promote positive maternal-infant bonding, global and targeted interventions in the perinatal period may benefit from targeting maternal psychopathology, perceived lack of social support, and coping with difficult infant temperament.
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Depresión Posparto , Relaciones Madre-Hijo , Niño , Femenino , Lactante , Embarazo , Humanos , Preescolar , Estudios Transversales , Australia , Depresión Posparto/diagnóstico , Depresión Posparto/prevención & control , Madres , Apego a ObjetosRESUMEN
Child maltreatment rates remain unacceptably high and rates are likely to escalate as COVID-related economic problems continue. A comprehensive and evidence-building approach is needed to prevent, detect and intervene where child maltreatment occurs. This review identifies key challenges in definitions, overviews the latest data on prevalence rates, reviews risk and protective factors, and examines common long-term mental health outcomes for children who experience maltreatment. The review takes a systems approach to child maltreatment outcomes through its focus on the overall burden of disease, gene-environment interactions, neurobiological mechanisms and social ecologies linking maltreatment to mental ill-health. Five recommendations relating to the accurate measurement of trends, research on brain structures and processes, improving the reach and impact of teleservices for detecting, preventing and treating child maladjustment, community-based approaches, and building population-focused multidisciplinary alliances and think tanks are presented.
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COVID-19 , Maltrato a los Niños , Trastornos Mentales , Niño , Humanos , Salud Mental , COVID-19/prevención & control , Maltrato a los Niños/prevención & control , Maltrato a los Niños/psicología , Trastornos Mentales/epidemiología , Trastornos Mentales/prevención & control , PrevalenciaRESUMEN
Contemporary theories of early development and emerging child psychopathology all posit a major, if not central role for physiological responsiveness. To understand infants' potential risk for emergent psychopathology, consideration is needed to both autonomic reactivity and environmental contexts (e.g., parent-child interactions). The current study maps infants' arousal during the face-to-face still-face paradigm using skin conductance (n = 255 ethnically-diverse mother-infant dyads; 52.5% girls, mean infant age = 7.4 months; SD = 0.9 months). A novel statistical approach was designed to model the potential build-up of nonlinear counter electromotive force over the course of the task. Results showed a significant increase in infants' skin conductance between the Baseline Free-play and the Still-Face phase, and a significant decrease in skin conductance during the Reunion Play when compared to the Still-Face phase. Skin conductance during the Reunion Play phase remained significantly higher than during the Baseline Play phase; indicating that infants had not fully recovered from the mild social stressor. These results further our understanding of infant arousal during dyadic interactions, and the role of caregivers in the development of emotion regulation during infancy.
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Expresión Facial , Relaciones Madre-Hijo , Lactante , Femenino , Humanos , Masculino , Relaciones Madre-Hijo/psicología , Madres/psicología , Relaciones Padres-Hijo , Sistema Nervioso Simpático , Conducta del Lactante/psicologíaRESUMEN
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that was first identified in December 2019, in Wuhan, China was found to be the etiological agent for a novel respiratory infection that led to a Coronavirus Induced Disease named COVID-19. The disease spread to pandemic magnitudes within a few weeks and since then we have been dealing with several waves across the world, due to the emergence of variants and novel mutations in this RNA virus. A direct outcome of these variants apart from the spike of cases is the diverse disease presentation and difficulty in employing effective diagnostic tools apart from confusing disease outcomes. Transmissibility rates of the variants, host response, and virus evolution are some of the features found to impact COVID-19 disease management. In this review, we will discuss the emerging variants of SARS-CoV-2, notable mutations in the viral genome, the possible impact of these mutations on detection, disease presentation, and management as well as the recent findings in the mechanisms that underlie virus-host interaction. Our aim is to invigorate a scientific debate on how pathogenic potential of the new pandemic viral strains contributes toward development in the field of virology in general and COVID-19 disease in particular.
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Arboviruses are some of the important causative agents of mosquito-mediated viral diseases. These viruses are transmitted between vector and host during the blood meal. Upon viral entry, host replication machinery is hijacked, supporting new virus particle production and thereby allowing viral survival in the host. In this process, host proteins interact with viral proteins to either facilitate viral replication, or they may provide antiviral defense mechanisms. In this study, we analyzed the impact of chikungunya virus (CHIKV) infection on the global proteome of Dicer active Aedes albopictus cells during the early and late time points of infection. We utilized a bottom-up approach of global proteomics analysis, and we used label-free quantitative mass spectrometry to identify the global protein signatures of Ae. albopictus at two different time points upon CHIKV infection. The mass spectrometry data analysis of the early time point revealed that proteins belonging to pathways such as translation, RNA processing, and cellular metabolic processes were less in abundance, whereas those belonging to pathways such as cellular catabolic process and organic substance transport were significantly abundant. At later time points, proteins belonging to pathways such as cellular metabolic processes, primary metabolic process, organonitrogen compound metabolic process, and organic substance metabolic process were found to be decreased in their presence, whereas those belonging to pathways such as RNA processing, gene expression, macromolecule metabolic processing, and nitrogen compound metabolic processing were found to be abundant during CHIKV infection, indicating that modulation in gene expression favoring cell survival occurs at a later time point, suggesting a survival strategy of Aedes cells to counter prolonged CHIKV infection.
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Genome-wide association studies (GWASs) show that genetic factors contribute to the risk of severe coronavirus disease 2019 (COVID-19) and blood analyte levels. Here, we utilize GWAS summary statistics to study the shared genetic influences (pleiotropy) between severe COVID-19 and 344 blood analytes at the genome, gene, and single-nucleotide polymorphism (SNP) levels. Our pleiotropy analyses genetically link blood levels of 71 analytes to severe COVID-19 in at least one of the three levels of investigation-suggesting shared biological mechanisms or causal relationships. Six analytes (alanine aminotransferase, alkaline phosphatase, apolipoprotein B, C-reactive protein, triglycerides, and urate) display evidence of pleiotropy with severe COVID-19 at all three levels. Causality analyses indicate that higher triglycerides levels causally increase the risk of severe COVID-19, thereby providing important support for the use of lipid-lowering drugs such as statins and fibrates to prevent severe COVID-19.