Infant neurodevelopment during the COVID-19 pandemic: Associations with maternal pandemic-related experiences, parenting stress, and self-efficacy.

BACKGROUND: Although pandemic-related experiences have been linked to the psychological well-being of mothers, the effects of the COVID-19 pandemic on infant neurodevelopmental outcomes have not been sufficiently studied. AIMS: To assess whether maternal COVID-19-related experiences (i.e., COVID-19-related health, risk, resource worries, and feelings of grief), parenting stress, and maternal self-efficacy are associated with infant neurodevelopment as measured by the Ages and Stages Questionnaire, Third Edition (ASQ-3) maternal report when infants were between 8 to 10 months of age. Furthermore, this study examined the moderating effect of maternal self-efficacy between maternal COVID-19-related experiences and infant neurodevelopment. METHODS: This cross-sectional study included 122 women who were drawn from the Perinatal Experiences and COVID-19 Effects (PEACE) Study, with online surveys administered between November 2020 and August 2022. RESULTS: After controlling for maternal anxiety and depression symptoms and demographic factors, hierarchical regression analysis indicated that parenting stress showed no effect on ASQ-3 scores. However, more adverse COVID-19-related experiences and higher levels of maternal self-efficacy were associated with better infant neurodevelopment. Moreover, there was a significant interaction effect between maternal self-efficacy and COVID-19-related experiences on infant neurodevelopment. For mothers with moderate to high levels of self-efficacy, more adverse COVID-19-related experiences were associated with better infant neurodevelopment. For mothers with low levels of self-efficacy, more adverse COVID-19-related experiences were associated with poorer developmental outcomes in infants. CONCLUSIONS: Under adverse conditions, confidence in caregiving may afford more optimal infant neurodevelopment. Interventions aimed at fostering maternal self-efficacy and addressing specific stressors can be valuable in promoting positive developmental trajectories for infants born during the pandemic.

A Pilot Randomized Controlled Trial of Augmented Reality Just-in-Time Guidance for the Performance of Rugged Field Procedures.

INTRODUCTION: Medical resuscitations in rugged prehospital settings require emergency personnel to perform high-risk procedures in low-resource conditions. Just-in-Time Guidance (JITG) utilizing augmented reality (AR) guidance may be a solution. There is little literature on the utility of AR-mediated JITG tools for facilitating the performance of emergent field care. STUDY OBJECTIVE: The objective of this study was to investigate the feasibility and efficacy of a novel AR-mediated JITG tool for emergency field procedures. METHODS: Emergency medical technician-basic (EMT-B) and paramedic cohorts were randomized to either video training (control) or JITG-AR guidance (intervention) groups for performing bag-valve-mask (BVM) ventilation, intraosseous (IO) line placement, and needle-decompression (Needle-d) in a medium-fidelity simulation environment. For the interventional condition, subjects used an AR technology platform to perform the tasks. The primary outcome was participant task performance; the secondary outcomes were participant-reported acceptability. Participant task score, task time, and acceptability ratings were reported descriptively and compared between the control and intervention groups using chi-square analysis for binary variables and unpaired t-testing for continuous variables. RESULTS: Sixty participants were enrolled (mean age 34.8 years; 72% male). In the EMT-B cohort, there was no difference in average task performance score between the control and JITG groups for the BVM and IO tasks; however, the control group had higher performance scores for the Needle-d task (mean score difference 22%; P = .01). In the paramedic cohort, there was no difference in performance scores between the control and JITG group for the BVM and Needle-d tasks, but the control group had higher task scores for the IO task (mean score difference 23%; P = .01). For all task and participant types, the control group performed tasks more quickly than in the JITG group. There was no difference in participant usability or usefulness ratings between the JITG or control conditions for any of the tasks, although paramedics reported they were less likely to use the JITG equipment again (mean difference 1.96 rating points; P = .02). CONCLUSIONS: This study demonstrated preliminary evidence that AR-mediated guidance for emergency medical procedures is feasible and acceptable. These observations, coupled with AR's promise for real-time interaction and on-going technological advancements, suggest the potential for this modality in training and practice that justifies future investigation.

Suicidality associated with decreased help-seeking attitudes in college students: Implications for identifying and treating at-risk students.

Suicide is a leading cause of death in college-aged youth, yet only half of all college students report engaging in professional mental health help-seeking. We examined how the various aspects of young adults' suicidality were associated with their openness to pursue professional mental health care in the future (i.e., "future help-seeking intentions"). Multilevel binary logistic regressions were tested in a sample of 24,446 U.S. college undergraduates with suicidality. The moderating effect of past service utilization on future help-seeking intentions was also tested. Strikingly, young people reporting past-year suicidal ideation, past-year suicidal attempts, and self-reported likelihood of a future suicide attempt demonstrated decreased likelihood of future help-seeking intentions, while those reporting prior diagnosis of a mental health condition and/or past service utilization demonstrated an increased likelihood. Past service utilization also significantly moderated the effect of suicide disclosure, such that youth reporting prior disclosure and prior professional treatment-seeking demonstrated greater odds of future help-seeking intentions relative to those who had disclosed suicidality but never utilized professional services. In order to mitigate the mental health crisis facing youth, further exploration is necessary to understand why students with suicidality do not report openness to seek help. It is also imperative to develop and implement novel strategies to identify at-risk students, understand and alleviate relevant barriers to treatment, and promote positive help-seeking attitudes and behaviors.

Prenatal mental health and emotional experiences during the pandemic: associations with infant neurodevelopment screening results.

BACKGROUND: This study determined whether parental mental health and emotional experiences during the prenatal period were linked to infant developmental outcomes through the Ages and Stages Questionnaire (ASQ-3) at 8-10 months. METHODS: Participants included 133 individuals who were living in the US and were pregnant or had given birth within 6 months prior to enrollment. Respondents were majority White with high education and income levels. Online surveys were administered from May 2020 to September 2021; follow-up surveys were administered from November 2020 to August 2022. RESULTS: Parent generalized anxiety symptoms were positively associated with infant communication (ß = 0.34, 95% CI [0.15, 1.76], p < 0.05), while parent-fetal bonding was positively associated with infant communication (ß = 0.20, 95% CI [0.05, 0.76], p < 0.05) and personal-social performance (ß = 0.20, 95% CI [0.04, 0.74], p < 0.05). COVID-19-related worry was negatively associated with infant communication (ß = -0.30, 95% CI [-0.75, -0.12], p < 0.05) and fine motor performance (ß = -0.25, 95% CI [-0.66, -0.03], p < 0.05). CONCLUSION: Parent mental health and emotional experiences may contribute to infant developmental outcomes in high risk conditions such as a pandemic. IMPACT STATEMENT: Maternal SARS-CoV-2 infection has been evaluated in relation to child outcomes, however, parent psychosocial experiences should not be overlooked when considering pandemic risks to child development. Specific prenatal mental health and pandemic-related emotional experiences are associated with infant developmental performance, as assessed by the Ages and Stages. Questionnaire (ASQ-3) at 8 to 10 months old. Findings indicate that parental prenatal anxiety and emotional experiences from the pandemic should be assessed when evaluating child developmental delays.

Effect of cryopreservation on CD4+ T cell subsets in foreskin tissue.

Voluntary medical male circumcision (VMMC) reduces HIV acquisition by at least 60%, but the determinants of HIV susceptibility in foreskin tissues are incompletely understood. Flow cytometry is a powerful tool that helps us understand tissue immune defenses in mucosal tissue like the inner foreskin, but foreskin flow cytometry has only been validated using fresh tissue samples. This restricts immune analyses to timepoints immediately after surgical acquisition and hinders research in this area. We compared fresh analysis with whole tissue cryopreservation and later thawing and digestion to analyze CD4+ T cell populations relevant to HIV susceptibility (CCR5, CD25, CD127, CCR4, CXCR3, CCR6, CCR10, HLA-DR, and CD38). Eight foreskin samples from HIV-negative males aged >18 years were collected after VMMC. For each sample, half the foreskin was immediately cryopreserved for later digestion and flow cytometry analysis, while the remaining tissues were analyzed fresh. We demonstrate no significant impact of cryopreservation on CD4+ T cell expression of CD25, CCR4, CCR6, HLA-DR, CCR10, or CD127. Although expression levels of CCR5, CD38, and CXCR3 were increased after cryopreservation, the relative ranking of participants was retained. In conclusion, cryopreserved foreskin tissues may be suitable for subsequent digestion and flow cytometry phenotyping of HIV-susceptible T cell populations.

Co-Packaged PARP inhibitor and photosensitizer for targeted photo-chemotherapy of 3D ovarian cancer spheroids.

BACKGROUND: Within the last decade, poly(ADP-ribose) polymerase inhibitors (PARPi) have emerged in the clinic as an effective treatment for numerous malignancies. Preclinical data have demonstrated powerful combination effects of PARPi paired with photodynamic therapy (PDT), which involves light-activation of specialized dyes (photosensitizers) to stimulate cancer cell death through reactive oxygen species generation. RESULTS: In this report, the most potent clinical PARP inhibitor, talazoparib, is loaded into the core of a polymeric nanoparticle (NP-Tal), which is interfaced with antibody-photosensitizer conjugates (photoimmunoconjugates, PICs) to form PIC-NP-Tal. In parallel, a new 3D fluorescent coculture model is developed using the parental OVCAR-8-DsRed2 and the chemo-resistant subline, NCI/ADR-RES-EGFP. This model enables quantification of trends in the evolutionary dynamics of acquired chemoresistance in response to various treatment regimes. Results reveal that at a low dosage (0.01 µM), NP-Tal kills the parental cells while sparing the chemo-resistant subline, thereby driving chemoresistance. Next, PIC-NP-Tal and relevant controls are evaluated in the 3D coculture model at multiple irradiation doses to characterize effects on total spheroid ablation and relative changes in parental and subline cell population dynamics. Total spheroid ablation data shows potent combination effects when PIC and NP-Tal are co-administered, but decreased efficacy with the conjugated formulation (PIC-NP-Tal). Analysis of cell population dynamics reveals that PIC, BPD + NP-Tal, PIC + NP-Tal, and PIC-NP-Tal demonstrate selection pressures towards chemoresistance. CONCLUSIONS: This study provides key insights into manufacturing parameters for PARPi-loaded nanoparticles, as well as the potential role of PDT-based combination therapies in the context of acquired drug resistance.

Synthesis of Phenol-Pyridinium Salts Enabled by Tandem Electron Donor-Acceptor Complexation and Iridium Photocatalysis.

Herein, we describe a dual photocatalytic system to synthesize phenol-pyridinium salts using visible light. Utilizing both electron donor-acceptor (EDA) complex and iridium(III) photocatalytic cycles, the C-N cross-coupling of unprotected phenols and pyridines proceeds in the presence of oxygen to furnish pyridinium salts. Photocatalytic generation of phenoxyl radical cations also enabled a nucleophilic aromatic substitution (SNAr) of a fluorophenol with an electron-poor pyridine. Spectroscopic experiments were conducted to probe the mechanism and reaction selectivity. The unique reactivity of these phenol-pyridinium salts were displayed in several derivatization reactions, providing rapid access to a diverse chemical space.

Insertive vaginal sex is associated with altered penile immunology and enrichment of Gardnerella vaginalis in uncircumcised Ugandan men.

PROBLEM: HIV susceptibility is linked to the penile immune milieu (particularly IL-8 levels) and microbiome. The effects of insertive vaginal sex itself on penile immunology and microbiota are not well described. METHOD OF STUDY: We compared the immune milieu and microbiology of the coronal sulcus (CS) and distal urethra in 47 uncircumcised Ugandan men reporting ever (n = 42) or never (n = 5) having had vaginal intercourse. Soluble immune factors were assayed by multiplex ELISA, and penile bacteria abundance by 16S rRNA qPCR and sequencing. Co-primary endpoints were penile levels of IL-8 and soluble E-cadherin. RESULTS: Independent of classical STIs, men reporting prior vaginal sex demonstrated elevated IL-8 levels in both the coronal sulcus (1.78 vs. 0.81 log10 pg/mL, p = .021) and urethra (2.93 vs. 2.30 log10 pg/mL; p = .003), with a strong inverse relationship between urethral IL-8 levels and the time from last vaginal sex (r = -0.436; p = .004). Vaginal sex was also associated with elevated penile IL-1α/ß and soluble E-cadherin (sEcad), a marker of epithelial disruption. Gardnerella vaginalis (Gv) was only present in the penile microbiome of men reporting prior vaginal sex, and urethral Gv absolute abundance was strongly associated with urethral inflammation (r = 0.556; p < .001); corynebacteria were enriched in the CS of men reporting no prior vaginal sex and were associated with reduced CS inflammation. CONCLUSIONS: Sexual intercourse was associated with sustained changes in penile immunology, potentially mediated through microbial alterations, in particular the urethral abundance of G. vaginalis. Future studies should further characterize the effects of sexual debut on penile bacteria and immunology.

Association of oral microbiome with oral human papillomavirus infection: a population study of the National Health and Nutrition Examination Survey, 2009-2012.

BACKGROUND: Oral human papillomavirus(HPV) infection and the oral microbiome are associated with oropharyngeal cancer. However, population-based data on the association of oral microbiome with oral HPV infection are limited. METHOD: We performed a cross-sectional analysis of 5,496 participants aged 20-59 in National Health and Nutrition Examination Surveys(NHANES):2009-2012. The association between either oral microbiome alpha diversity or beta diversity and oral HPV infection was assessed using multivariable logistic regression or principal coordinate analyses(PCoA) and multivariate analysis of variance(PERMANOVA). RESULTS: For alpha diversity, we found a lower number of observed Amplicon sequence variants(ASVs) (adjusted odds ratio[aOR] = 0.996; 95%CI = 0.992-0.999) and reduced Faith's Phylogenetic Diversity(aOR = 0.95; 95%CI = 0.90-0.99) associated with high-risk oral HPV infection in the overall population. This trend was observed in males for both high-risk and any oral HPV infection. Beta diversity showed differentiation of oral microbiome community by high-risk oral HPV infection as measured by Bray-Curtis dissimilarity (R2 = 0.054%; P = .029) and unweighted UniFrac distance (R2 = 0.046%; P = .045) among the overall population, and associations were driven by males. CONCLUSIONS: Both oral microbiome alpha diversity(within-sample richness and phylogenetic diversity) and beta diversity(heterogeneous dispersion of oral microbiome community) are associated with HPV infection. Longitudinal studies are needed to characterize the role of the microbiome in the natural history of oral HPV infection.

Communication Strategies to Improve Antibiotic Prescribing in Pediatric Urgent Care Centers.

OBJECTIVE: Urgent care (UC) clinicians frequently prescribe inappropriate antibiotics for upper respiratory illnesses. In a national survey, pediatric UC clinicians reported family expectations as a primary driver for prescribing inappropriate antibiotics. Communication strategies effectively reduce unnecessary antibiotics while increasing family satisfaction. We aimed to reduce inappropriate prescribing practices in otitis media with effusion (OME), acute otitis media (AOM), and pharyngitis in pediatric UC clinics by a relative 20% within 6 months using evidence-based communication strategies. METHODS: We recruited participants via e-mails, newsletters, and Webinars from pediatric and UC national societies. We defined antibiotic-prescribing appropriateness based on consensus guidelines. Family advisors and UC pediatricians developed script templates based on an evidence-based strategy. Participants submitted data electronically. We reported data using line graphs and shared deidentified data during monthly Webinars. We used χ 2 tests to evaluate change in appropriateness at the beginning and end of the study period. RESULTS: The 104 participants from 14 institutions submitted 1183 encounters for analysis in the intervention cycles. Using a strict definition of inappropriateness, overall inappropriate antibiotic prescriptions for all diagnoses trended downward from 26.4% to 16.6% ( P = 0.13). Inappropriate prescriptions trended upward in OME from 30.8% to 46.7% ( P = 0.34) with clinicians' increased use of "watch and wait" for this diagnosis. Inappropriate prescribing for AOM and pharyngitis improved from 38.6% to 26.5% ( P = 0.03) and 14.5% to 8.8% ( P = 0.44), respectively. CONCLUSIONS: Using templates to standardize communication with caregivers, a national collaborative decreased inappropriate antibiotic prescriptions for AOM and had downward trend in inappropriate antibiotic prescriptions for pharyngitis. Clinicians increased the inappropriate use of "watch and wait" antibiotics for OME. Future studies should evaluate barriers to the appropriate use of delayed antibiotic prescriptions.

Effect of vicarious discrimination on race-based stress symptoms among Asian American young adults during the COVID-19 pandemic.

OBJECTIVE: The COVID-19 pandemic has led to a rise in anti-Asian hate crimes in the United States. Previous work has established that experiencing racism increases one's dysfunctional anxiety and avoidance actions-key symptoms of race-based stress symptoms. However, the psychological impact of vicarious, or secondhand, discrimination (witnessing racism targeting one's own race group) remains less understood. METHOD: We tested the hypothesis that higher reported vicarious discrimination would be associated with higher levels of race-based stress symptoms reported by Asian American young adults (n = 135) during the pandemic using a cross-sectional analysis of the COVID-19 Adult Resilience Experiences Study (CARES). Starting in April 2020, CARES assessed sociodemographic characteristics and key psychometric scales in young adults through three waves of online surveys. RESULTS: Our multiple regression analysis showed vicarious discrimination significantly predicted race-based stress symptoms, even after controlling for direct discrimination (p < .01). This association remained significant after controlling for age, gender, subjective childhood family social status, and preexisting psychiatric disorders (p < .01). Our results demonstrate that regardless of the effect that direct discrimination might have on race-based stress symptoms, witnessing discrimination against members of one's own racial group is significantly associated with increased race-based stress symptoms (b = 2.68, p < .01). Social media was the most common source of vicarious discrimination, with one out of three participants in our sample reporting nearly daily exposure. CONCLUSION: Providers should intentionally create a space within the therapeutic setting to discuss the effects of vicarious discrimination. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Gut microbiome predictors of Escherichia coli sequence type 131 colonization and loss.

BACKGROUND: Escherichia coli sequence type 131 (ST131), specifically its fluoroquinolone-resistant H30R clade (ST131-H30R), is a global multidrug-resistant pathogen. The gut microbiome's role in ST131-H30R intestinal carriage is undefined. METHODS: Veterans and their household members underwent longitudinal fecal swab surveillance for ST131 in 2014-2018. The fecal microbiome was characterized by 16S rRNA qPCR and sequencing. We evaluated associations between ST131-H30R carriage and gut microbiome at baseline by random forest models to identify the most informative gut bacterial phyla and genera attributes for ST131 and ST131-H30R carriage status. Next, we assessed longitudinal associations between fecal microbiome and ST131-H30R carriage using a mixed-effects logistic regression with longitudinal measures. FINDINGS: Of the 519 participants, 78 were carriers of ST131, among whom 49 had ST131-H30R. At the baseline timepoint, H30R-positive participants had higher proportional abundances of Actinobacteria phylum (mean: 4.9% vs. 3.1%) than ST131-negative participants. H30R-positive participants also had higher abundances of Collinsella (mean: 2.3% vs. 1.1%) and lower abundances of Alistipes (mean: 2.1% vs. 2.6%) than ST131-negative participants. In the longitudinal analysis, Collinsella abundance correlated positively with ST131-H30R carriage status and negatively with the loss of ST131-H30R. Conversely, Alistipes corresponded with the loss and persistent absence of ST131-H30R even in the presence of a household exposure. INTERPRETATION: Abundances of specific fecal bacteria correlated with ST131-H30R carriage, persistence, and loss, suggesting their potential as targets for microbiome-based strategies to reduce carriage of ST131-H30R, a significant risk factor for invasive infections. FUNDING: This work was supported in part by National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers R21AI117654 and UM1AI104681 and the Office of Research and Development, Department of Veterans Affairs. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans Affairs.

Ecological correlates of three-dimensional muscle architecture within the dietarily diverse Strepsirrhini.

Analysis of muscle architecture, traditionally conducted via gross dissection, has been used to evaluate adaptive relationships between anatomical form and behavioral function. However, gross dissection cannot preserve three-dimensional relationships between myological structures for analysis. To analyze such data, we employ diffusible, iodine-based contrast-enhanced computed tomography (DiceCT) to explore the relationships between feeding ecology and masticatory muscle microanatomy in eight dietarily diverse strepsirrhines: allowing, for the first time, preservation of three-dimensional fascicle orientation and tortuosity across a functional comparative sample. We find that fascicle properties derived from these digital analyses generally agree with those measured from gross-dissected conspecifics. Physiological cross-sectional area was greatest in species with mechanically challenging diets. Frugivorous taxa and the wood-gouging species all exhibit long jaw adductor fascicles, while more folivorous species show the shortest relative jaw adductor fascicle lengths. Fascicle orientation in the parasagittal plane also seems to have a clear dietary association: most folivorous taxa have masseter and temporalis muscle vectors that intersect acutely while these vectors intersect obliquely in more frugivorous species. Finally, we observed notably greater magnitudes of fascicle tortuosity, as well as greater interspecific variation in tortuosity, within the jaw adductor musculature than in the jaw abductors. While the use of a single specimen per species precludes analysis of intraspecific variation, our data highlight the diversity of microanatomical variation that exists within the strepsirrhine feeding system and suggest that muscle architectural configurations are evolutionarily labile in response to dietary ecology-an observation to be explored across larger samples in the future.

Home away from home: international students' experiences during the COVID-19 pandemic and the role of US higher education.

Introduction: This study focuses on the impact of the COVID-19 pandemic on international students' overall experiences. Method: We interviewed 22 international students from 11 countries and 17 universities in the US who participated in a large longitudinal study that aims to understand the physical and emotional wellbeing of young adults during the COVID-19 pandemic. Guided by Bronfenbrenner's ecological model, the findings suggested that students were impacted by the COVID-19 pandemic at interpersonal, institutional, political, and personal levels. Results: The results showed that the pandemic exacerbated existing stressors such as the lack of social support from family, various visa regulations, competitive and limited job opportunities, discrimination and xenophobia, particularly toward students from Asia, and financial burdens. Additionally, the findings highlighted students' perceived loss of the "American dream" and the uneven return on investment due to the pandemic. Discussion: This study reveals the importance of US higher education institutions in supporting international students during the pandemic, particularly in terms of their sense of belonging. Recommendations for institutions drawn from the findings are proposed to better support international students during times of COVID-19 and beyond.

Long COVID and psychological distress in young adults: Potential protective effect of a prior mental health diagnosis.

BACKGROUND: Although young adulthood is a period characterized by marked psychological vulnerability, young adults are typically considered to be in good physical health and are therefore understudied with respect to the effects of COVID-19 infection and long COVID. The present study examined associations between post-acute sequelae of COVID-19 (PASC) and serious psychological distress during young adulthood, and tested whether prior mental health diagnosis moderated this association. METHODS: Participants were 44,652 young adults who completed the Spring 2022 administration of the American College Health Association-National College Health Assessment III (ACHA-NCHA). Blockwise logistic regressions tested the odds of meeting the clinical threshold for serious psychological distress. RESULTS: PASC was associated with 53 % increased likelihood of meeting the clinical threshold for serious psychological distress. Among young adults with a prior mental health diagnosis, PASC predicted 36 % increased odds of serious psychological distress; among those without a diagnosis, PASC predicted 81 % increased odds. LIMITATIONS: PASC was assessed using a single self-report item rather than a clinical diagnosis of specific symptomatology. The analyses were cross-sectional and relied on concurrent reports of PASC and psychological distress which precluded us from making claims regarding directionality of the associations. The outcome of generalized psychological distress limited us from generating targeted treatment recommendations. CONCLUSIONS: PASC may confer elevated psychological distress among young adults. The association of PASC to serious psychological distress was stronger in young adults without a mental health diagnosis than those with a diagnosis. Prior experience with mental illness may mitigate the psychological burden of long-term symptomatology.

Towards a youth mental health paradigm: a perspective and roadmap.

Most mental disorders have a typical onset between 12 and 25 years of age, highlighting the importance of this period for the pathogenesis, diagnosis, and treatment of mental ill-health. This perspective addresses interactions between risk and protective factors and brain development as key pillars accounting for the emergence of psychopathology in youth. Moreover, we propose that novel approaches towards early diagnosis and interventions are required that reflect the evolution of emerging psychopathology, the importance of novel service models, and knowledge exchange between science and practitioners. Taken together, we propose a transformative early intervention paradigm for research and clinical care that could significantly enhance mental health in young people and initiate a shift towards the prevention of severe mental disorders.

Transient fluid flow improves photoimmunoconjugate delivery and photoimmunotherapy efficacy.

Circulating drugs in the peritoneal cavity is an effective strategy for advanced ovarian cancer treatment. Photoimmunotherapy, an emerging modality with potential for the treatment of ovarian cancer, involves near-infrared light activation of antibody-photosensitizer conjugates (photoimmunoconjugates) to generate cytotoxic reactive oxygen species. Here, a microfluidic cell culture model is used to study how fluid flow-induced shear stress affects photoimmunoconjugate delivery to ovarian cancer cells. Photoimmunoconjugates are composed of the antibody, cetuximab, conjugated to the photosensitizer, and benzoporphyrin derivative. Longitudinal tracking of photoimmunoconjugate treatment under flow conditions reveals enhancements in subcellular photosensitizer accumulation. Compared to static conditions, fluid flow-induced shear stress at 0.5 and 1 dyn/cm2 doubled the cellular delivery of photoimmunoconjugates. Fluid flow-mediated treatment with three different photosensitizer formulations (benzoporphyrin derivative, photoimmunoconjugates, and photoimmunoconjugate-coated liposomes) led to enhanced phototoxicity compared to static conditions. This study confirms the fundamental role of fluid flow-induced shear stress in the anti-cancer effects of photoimmunotherapy.

Single-shot 3D photoacoustic computed tomography with a densely packed array for transcranial functional imaging.

Photoacoustic computed tomography (PACT) is emerging as a new technique for functional brain imaging, primarily due to its capabilities in label-free hemodynamic imaging. Despite its potential, the transcranial application of PACT has encountered hurdles, such as acoustic attenuations and distortions by the skull and limited light penetration through the skull. To overcome these challenges, we have engineered a PACT system that features a densely packed hemispherical ultrasonic transducer array with 3072 channels, operating at a central frequency of 1 MHz. This system allows for single-shot 3D imaging at a rate equal to the laser repetition rate, such as 20 Hz. We have achieved a single-shot light penetration depth of approximately 9 cm in chicken breast tissue utilizing a 750 nm laser (withstanding 3295-fold light attenuation and still retaining an SNR of 74) and successfully performed transcranial imaging through an ex vivo human skull using a 1064 nm laser. Moreover, we have proven the capacity of our system to perform single-shot 3D PACT imaging in both tissue phantoms and human subjects. These results suggest that our PACT system is poised to unlock potential for real-time, in vivo transcranial functional imaging in humans.

Early Outcomes of SARS-CoV-2 Infection in a Multisite Prospective Cohort of Inpatient Veterans.

Background: Over 870 000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have occurred among Veterans Health Administration users, and 24 000 have resulted in death. We examined early outcomes of SARS-CoV-2 infection in hospitalized veterans. Methods: In an ongoing, prospective cohort study, we enrolled veterans age ≥18 tested for SARS-CoV-2 and hospitalized at 15 Department of Veterans Affairs medical centers between February 2021 and June 2022. We estimated adjusted odds ratios (aORs), adjusted incidence rate ratios (aIRRs), and adjusted hazard ratios (aHRs) for maximum illness severity within 30 days of study entry (defined using the 4-category VA Severity Index for coronavirus disease 2019 [COVID-19]), as well as length of hospitalization and rehospitalization within 60 days, in relationship with demographic characteristics, Charlson comorbidity index (CCI), COVID-19 vaccination, and calendar period of enrollment. Results: The 542 participants included 329 (61%) who completed a primary vaccine series (with or without booster; "vaccinated"), 292 (54%) enrolled as SARS-CoV-2-positive, and 503 (93%) men, with a mean age of 64.4 years. High CCI scores (≥5) occurred in 61 (44%) vaccinated and 29 (19%) unvaccinated SARS-CoV-2-positive participants. Severe illness or death occurred in 29 (21%; 6% died) vaccinated and 31 (20%; 2% died) unvaccinated SARS-CoV-2-positive participants. SARS-CoV-2-positive inpatients per unit increase in CCI had greater multivariable-adjusted odds of severe illness (aOR, 1.21; 95% CI, 1.01-1.45), more hospitalization days (aIRR, 1.06; 95% CI, 1.03-1.10), and rehospitalization (aHR, 1.07; 95% CI, 1.01-1.12). Conclusions: In a cohort of hospitalized US veterans with SARS-CoV-2 infection, those with a higher CCI had more severe COVID-19 illness, more hospital days, and rehospitalization, after adjusting for vaccination status, age, sex, and calendar period.