Investigators used a case–control, test-negative design to assess the effectiveness of the BNT162b2 vaccine in adolescents for the prevention of Covid-19–related hospitalization, ICU admission, or ...receipt of life support. Among 445 case patients and 777 controls, of the 180 patients admitted to an ICU, only 2 had been fully vaccinated; all 7 deaths occurred in unvaccinated patients.
Background:
Apixaban is commonly used to prevent stroke in older adults with nonvalvular atrial fibrillation (AF). Although its package insert has specific dose reduction criteria, providers may dose ...reduce outside of these parameters based on clinical scenarios.
Objective:
The primary objective was to determine the incidence of apixaban off-label reduced dosing, while secondarily determining the safety and efficacy outcomes associated with such dosing.
Methods:
A retrospective analysis of patients aged 65 and older with orders for apixaban for AF was institutional review board (IRB)-approved and conducted across 3 academic medical centers. Patients receiving off-label reduced-dose apixaban (ie, “underdosed”) were matched to a cohort of patients dosed according to the package insert at the standard dosing (5 mg twice daily) using stratified random sampling. Secondary outcomes included 1-year incidence of major bleeding, clinically relevant non-major bleeding (CRNMB), stroke or transient ischemic attack (TIA), and mortality. The Fisher exact tests were used to compare between-group differences.
Results:
Of the 1172 patients meeting initial inclusion criteria, 201 (17%) were dosed off-label, with 175 (15%) “underdosed.” The 147 “underdosed” patients with documented follow-up were matched with 139 patients receiving standard Food and Drug Administration (FDA)-labeled dosing. There were no significant differences in incidence of stroke (2.7% vs 2.2%), major bleeding (0% vs 0.7%), and CRNMB (2.7% vs 1.4%) in the off-label reduced dosing versus standard dosing groups. All-cause mortality was higher in the off-label reduced-dose group (16 10.9% vs 2 1.4%, P < 0.05).
Conclusion and Relevance:
Older adults with nonvalvular AF are commonly prescribed lower-than-recommended doses of apixaban. However, no significant association was found between empiric off-label reduced dosing and stroke or bleeding outcomes.
Compassion may be a particularly important component of a sexual relationship as it facilitates needed self-awareness, understanding, and connection to frame deeply intimate expressions of sexual ...emotion and vulnerability. Given the lack of research on how broad concepts of compassionate elements may be linked to sexual well-being, we examine how mindfulness (an ability to maintain awareness in the present moment), compassionate relational attitudes (i.e., accessibility, responsiveness, and engagement), and compassionate relational behaviors (i.e., forgiveness and gratitude), are linked to sexual well-being (sexual harmony, orgasm consistency, and sexual frequency), and sexual mindfulness (a state of being mindful during sex) for oneself and one's partner.
We constructed an actor partner structural equation model with newly married couples (
= 2,111) and regressed sexual outcomes at time 1 and time 2 on each partner's compassionate attitudes, behaviors and mindfulness reported at time 1.
Results showed that cross-sectionally, nearly all elements of one's compassion related to one's own sexual well-being for both partners. Strongest paths included positive significant relations for women between mindfulness and non-judgment and from compassionate relational attitudes and behaviors to sexual harmony. Men's compassionate behaviors were positively related to their own sexual awareness. Perhaps more importantly, women's and men's compassionate behaviors had significant effects on their partner's sexual well-being longitudinally.
Implications include an emphasis on compassion as a key mechanism that can increase sexual satisfaction and strengthen relationships, particularly in the critical time of early marriage where patterns of interconnectedness are being established.
Urban environments expose wildlife to levels of anthropogenic noise they would not experience in rural areas (e.g., traffic noise), and research suggests that many species adjust their acoustic ...signals for optimal transmission in urban soundscapes. However, our understanding of anuran (order Anura) responses to noise pollution in urban environments of the southeastern United States is limited, particularly for species that can breed during winter. Our goal was to examine how vocal anuran advertisement call characteristics during winter varied with increasing distance from roadways in bottomland hardwoods of Louisiana, USA. We deployed acoustic recording units at two sites (i.e., rural and urban) perpendicular to Interstate 10 at 200‐, 400‐, and 600‐m intervals (i.e., close, middle, and far) from November 2019 to January 2020. We detected Cajun Chorus Frogs (Pseudacris fouquettei) and Cricket Frogs (Acris spp.) at our rural site, and only detected Cricket Frogs at our urban site. At the rural site, Cajun Chorus Frogs produced longer duration notes at the far location compared to the middle location. At the urban site, Cricket Frogs produced higher dominant frequency calls at the close location compared to the far and middle locations and longer duration notes at the far location compared to the close location. We were unable to account for additional factors in our models (e.g., temperature, noise levels), but our results generally align with previous research. Our study provides baseline data for future research to examine the potential effects of traffic noise on winter advertisement calls in locations with similar environmental conditions and species.
Our goal was to examine how vocal anuran advertisement call characteristics during winter varied with increasing distance from Interstate 10 (i.e., close, middle, and far locations) at a rural and urban site in Louisiana, USA. We found that Cajun Chorus Frogs (Pseudacris fouquettei) and Cricket Frogs (Acris spp.) detected at the rural site had few differences in their advertisement call characteristics across locations, but that Cricket Frogs at the urban site had advertisement call characteristics that varied in dominant frequency and duration across locations.
Abstract
Background
In the United States, influenza activity during the 2021–2022 season was modest and sufficient enough to estimate influenza vaccine effectiveness (VE) for the first time since the ...beginning of the coronavirus disease 2019 pandemic. We estimated influenza VE against laboratory-confirmed outpatient acute illness caused by predominant A(H3N2) viruses.
Methods
Between October 2021 and April 2022, research staff across 7 sites enrolled patients aged ≥6 months seeking outpatient care for acute respiratory illness with cough. Using a test-negative design, we assessed VE against influenza A(H3N2). Due to strong correlation between influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, participants who tested positive for SARS-CoV-2 were excluded from VE estimations. Estimates were adjusted for site, age, month of illness, race/ethnicity, and general health status.
Results
Among 6260 participants, 468 (7%) tested positive for influenza only, including 440 (94%) for A(H3N2). All 206 sequenced A(H3N2) viruses were characterized as belonging to genetic group 3C.2a1b subclade 2a.2, which has antigenic differences from the 2021–2022 season A(H3N2) vaccine component that belongs to clade 3C.2a1b subclade 2a.1. After excluding 1948 SARS-CoV-2–positive patients, 4312 patients were included in analyses of influenza VE; 2463 (57%) were vaccinated against influenza. Effectiveness against A(H3N2) for all ages was 36% (95% confidence interval, 20%–49%) overall.
Conclusions
Influenza vaccination in 2021–2022 provided protection against influenza A(H3N2)-related outpatient visits among young persons.
Influenza activity increased during 2021–2022 in the US for the first time since the COVID-19 pandemic, which allowed us to estimate influenza vaccine effectiveness. In the 2021–2022 season, influenza vaccines reduced the risk of influenza A(H3N2)-associated illness by about one-third.
Legionella pneumophila, the causative agent of Legionnaires' disease, invades and proliferates within a diverse range of free‐living amoeba in the environment, but upon transmission to humans, the ...bacteria hijack alveolar macrophages. Intracellular proliferation of L. pneumophila in two evolutionarily distant hosts is facilitated by bacterial exploitation of conserved host processes that are targeted by bacterial protein effectors injected into the host cell. A key aspect of microbe–host interaction is microbial extraction of nutrients from the host, but understanding of this is still limited. AnkB functions as a nutritional virulence factor and promotes host proteasomal degradation of polyubiquitinated proteins generating gratuitous levels of limiting host cellular amino acids. Legionella pneumophila is auxotrophic for several amino acids including cysteine, which is a metabolically preferred source of carbon and energy during intracellular proliferation, but is limiting in both amoebae and humans. We propose that synchronization of bacterial amino acids auxotrophy with the host is a driving force in pathogenic evolution and nutritional adaptation of L. pneumophila and other intracellular bacteria to life within the host cell. Understanding microbial strategies of nutrient generation and acquisition in the host will provide novel antimicrobial strategies to disrupt pathogen access to essential sources of carbon and energy.
This study quantified eight, small molecule neurotransmitters collected simultaneously from prefrontal cortex of C57BL/6J mouse (n=23) during wakefulness and during isoflurane anesthesia (1.3%). ...Using isoflurane anesthesia as an independent variable enabled evaluation of the hypothesis that isoflurane anesthesia differentially alters concentrations of multiple neurotransmitters and their interactions. Machine learning was applied to reveal higher order interactions among neurotransmitters. Using a between-subjects design, microdialysis was performed during wakefulness and during anesthesia. Concentrations (nM) of acetylcholine, adenosine, dopamine, GABA, glutamate, histamine, norepinephrine, and serotonin in the dialysis samples are reported (mean ± SD). Relative to wakefulness, acetylcholine concentration was lower during isoflurane anesthesia (1.254 ± 1.118 versus 0.401 ± 0.134, P=0.009), and concentrations of adenosine (29.456 ± 29.756 versus 101.321 ± 38.603, P<0.001), dopamine (0.0578 ± 0.0384 versus 0.113 ± 0.084, P=0.036), and norepinephrine (0.126 ± 0.080 versus 0.219 ± 0.066, P=0.010) were higher during anesthesia. Isoflurane reconfigured neurotransmitter interactions in prefrontal cortex, and the state of isoflurane anesthesia was reliably predicted by prefrontal cortex concentrations of adenosine, norepinephrine, and acetylcholine. A novel finding to emerge from machine learning analyses is that neurotransmitter concentration profiles in mouse prefrontal cortex undergo functional reconfiguration during isoflurane anesthesia. Adenosine, norepinephrine, and acetylcholine showed high feature importance, supporting the interpretation that interactions among these three transmitters may play a key role in modulating levels of cortical and behavioral arousal.
Legionella pneumophila is an aquatic organism that interacts with amoebae and ciliated protozoa as the natural hosts, and this interaction plays a central role in bacterial ecology and infectivity. ...Upon transmission to humans, L. pneumophila infect and replicate within alveolar macrophages causing pneumonia. Intracellular proliferation of L. pneumophila within the two evolutionarily distant hosts is facilitated by bacterial exploitation of evolutionarily conserved host processes that are targeted by bacterial protein effectors injected into the host cell by the Dot/Icm type VIB translocation system. Although cysteine is semi-essential for humans and essential for amoeba, it is a metabolically favorable source of carbon and energy generation by L. pneumophila. To counteract host limitation of cysteine, L. pneumophila utilizes the AnkB Dot/Icm-translocated F-box effector to promote host proteasomal degradation of polyubiquitinated proteins within amoebae and human cells. Evidence indicates ankB and other Dot/Icm-translocated effector genes have been acquired through inter-kingdom horizontal gene transfer.
ABSTRACT
Background
The 2022–23 US influenza season peaked early in fall 2022.
Methods
Late‐season influenza vaccine effectiveness (VE) against outpatient, laboratory‐confirmed influenza was ...calculated among participants of the US Influenza VE Network using a test‐negative design.
Results
Of 2561 participants enrolled from December 12, 2022 to April 30, 2023, 91 laboratory‐confirmed influenza cases primarily had A(H1N1)pdm09 (6B.1A.5a.2a.1) or A(H3N2) (3C.2a1b.2a.2b). Overall, VE was 30% (95% confidence interval −9%, 54%); low late‐season activity precluded estimation for most subgroups.
Conclusions
2022–23 late‐season outpatient influenza VE was not statistically significant. Genomic characterization may improve the identification of influenza viruses that circulate postinfluenza peak.
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