The immune response to COVID-19: Does sex matter?

The coronavirus disease 2019 (COVID-19) pandemic has created unprecedented challenges worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 and has a complex interaction with the immune system, including growing evidence of sex-specific differences in the immune response. Sex-disaggregated analyses of epidemiological data indicate that males experience more severe symptoms and suffer higher mortality from COVID-19 than females. Many behavioural risk factors and biological factors may contribute to the different immune response. This review examines the immune response to SARS-CoV-2 infection in the context of sex, with emphasis on potential biological mechanisms explaining differences in clinical outcomes. Understanding sex differences in the pathophysiology of SARS-CoV-2 infection will help promote the development of specific strategies to manage the disease.

Neutrophil/Lymphocyte Ratio in Patients Undergoing Noncardiac Surgery After Coronary Stent Implantation.

OBJECTIVE: Perioperative cell count-associated predictors, including the neutrophil/lymphocyte ratio (N/LR) and platelet/lymphocyte ratio (P/LR), are associated with poor clinical outcomes including myocardial injury. Study investigators aimed to examine the association among the perioperative N/LR, P/LR, and postoperative major adverse cardiovascular and cerebral events (MACCE) after noncardiac surgery in patients with drug-eluting stent (DES) insertion. DESIGN: Retrospective and observational. SETTING: Single university hospital. PARTICIPANTS: The study comprised 965 patients who underwent noncardiac surgery within 6 months after DES implantation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline perioperative clinical parameters, including N/LR and P/LR measured before surgery, immediately after surgery, and on postoperative day (POD) 1, were obtained. MACCE was defined as a composite of nonfatal myocardial infarction, coronary revascularization, nonhemorrhagic stroke, and pulmonary embolism within 1 month after surgery. Multivariate logistic regression analysis and propensity score matching were used to identify predictors of MACCE after surgery. MACCE occurred in 67 patients (6.9%) and was more common in patients with N/LR on POD 1 >4.3 (multivariable-adjusted odds ratio [OR] 2.03, 95% confidence interval [CI] 1.12-2.79; p = 0.040 and as a continuous N/LR [OR 1.17, 95% CI 1.08-1.27; p < 0.001]). This association was consistent after propensity score matching and was stronger when the antiplatelet agent was stopped before surgery (OR 3.02, 95% CI 2.14-4.48; p = 0.006 for stopping dual antiplatelet therapy). CONCLUSIONS: In patients undergoing noncardiac surgery within 6 months after DES implantation, elevated N/LR on POD 1 is independently associated with postoperative MACCE. Elevated postoperative N/LR as a marker of systemic inflammation may help to predict the development of MACCE in these high-risk patients.

Spiritual Care in the Intensive Care Unit: A Narrative Review.

Spiritual care is an important component of high-quality health care, especially for critically ill patients and their families. Despite evidence of benefits from spiritual care, physicians and other health-care providers commonly fail to assess and address their patients' spiritual care needs in the intensive care unit (ICU). In addition, it is common that spiritual care resources that can improve both patient outcomes and family member experiences are underutilized. In this review, we provide an overview of spiritual care and its role in the ICU. We review evidence demonstrating the benefits of, and persistent unmet needs for, spiritual care services, as well as the current state of spiritual care delivery in the ICU setting. Furthermore, we outline tools and strategies intensivists and other critical care medicine health-care professionals can employ to support the spiritual well-being of patients and families, with a special focus on chaplaincy services.

Neuraminidase as an enzymatic marker for detecting airborne Influenza virus and other viruses.

Little information is available regarding the effectiveness of air samplers to collect viruses and regarding the effects of sampling processes on viral integrity. The neuraminidase enzyme is present on the surface of viruses that are of agricultural and medical importance. It has been demonstrated that viruses carrying this enzyme can be detected using commercial substrates without having to process the sample by methods such as RNA extraction. This project aims at evaluating the effects of 3 aerosol-sampling devices on the neuraminidase enzyme activity of airborne viruses. The purified neuraminidase enzymes from Clostridium perfringens, a strain of Influenza A (H1N1) virus, the FluMist influenza vaccine, and the Newcastle disease virus were used as models. The neuraminidase models were aerosolized in aerosol chambers and sampled with 3 different air samplers (SKC BioSampler, 3-piece cassettes with polycarbonate filters, and Coriolis µ) to assess the effect on neuraminidase enzyme activity. Our results demonstrated that Influenza virus and Newcastle disease virus neuraminidase enzymes are resistant to aerosolization and sampling with all air samplers tested. Moreover, we demonstrated that the enzymatic neuraminidase assay is as sensitive as RT-qPCR for detecting low concentrations of Influenza virus and Newcastle disease virus. Therefore, given the sensitivity of the assay and its compatibility with air sampling methods, viruses carrying the neuraminidase enzyme can be rapidly detected from air samples using neuraminidase activity assay without having to preprocess the samples.

Sex-specific outcomes in cancer therapy: the central role of hormones.

Sex hormones play a pivotal role in modulating various physiological processes, with emerging evidence underscoring their influence on cancer progression and treatment outcomes. This review delves into the intricate relationship between sex hormones and cancer, elucidating the underlying biological mechanisms and their clinical implications. We explore the multifaceted roles of estrogen, androgens, and progesterone, highlighting their respective influence on specific cancers such as breast, ovarian, endometrial, and prostate. Special attention is given to estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) tumors, androgen receptor signaling, and the dual role of progesterone in both promoting and inhibiting cancer progression. Clinical observations reveal varied treatment responses contingent upon hormonal levels, with certain therapies like tamoxifen, aromatase inhibitors, and anti-androgens demonstrating notable success. However, disparities in treatment outcomes between males and females in hormone-sensitive cancers necessitate further exploration. Therapeutically, the utilization of hormone replacement therapy (HRT) during cancer treatments presents both potential risks and benefits. The promise of personalized therapies, tailored to an individual's hormonal profile, offers a novel approach to optimizing therapeutic outcomes. Concurrently, the burgeoning exploration of new drugs and interventions targeting hormonal pathways heralds a future of more effective and precise treatments for hormone-sensitive cancers. This review underscores the pressing need for a deeper understanding of sex hormones in cancer therapy and the ensuing implications for future therapeutic innovations.

Designing and developing a sensitive and specific SARS-CoV-2 RBD IgG detection kit for identifying positive human samples.

BACKGROUND: More than 3 y into the coronavirus 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to undergo mutations. In this context, the Receptor Binding Domain (RBD) is the most antigenic region among the SARS-CoV-2 Spike protein and has emerged as a promising candidate for immunological development. We designed an IgG-based indirect enzyme-linked immunoassay (ELISA) kit based on recombinant RBD, which was produced from the laboratory to 10 L industry scales in Pichia pastoris. METHODS: A recombinant-RBD comprising 283 residues (31 kDa) was constructed after epitope analyses. The target gene was initially cloned into an Escherichia coli TOP10 genotype and transformed into Pichia pastoris CBS7435 muts for protein production. Production was scaled up in a 10 L fermenter after a 1 L shake-flask cultivation. The product was ultrafiltered and purified using ion-exchange chromatography. IgG-positive human sera for SARS-CoV-2 were employed by an ELISA test to evaluate the antigenicity and specific binding of the produced protein. RESULTS: Bioreactor cultivation yielded 4 g/l of the target protein after 160 h of fermentation, and ion-exchange chromatography indicated a purity > 95%. A human serum ELISA test was performed in 4 parts, and the ROC area under the curve (AUC) was > 0.96 for each part. The mean specificity and sensitivity of each part was 100% and 91.5%, respectively. CONCLUSION: A highly specific and sensitive IgG-based serologic kit was developed for improved diagnostic purposes in patients with COVID-19 after generating an RBD antigen in Pichia pastoris at laboratory and 10 L fermentation scales.

Serum bicarbonate levels and gait abnormalities in older adults: a cross-sectional study.

Metabolic acidosis is associated with impaired physical function in patients with chronic kidney disease (CKD) and older adults. However, whether acidosis is associated with gait abnormalities has received little attention. In a cohort of 323 community-dwelling adults ≥ 65 years old who underwent quantitative gait analysis, we examined associations of serum bicarbonate with eight individual gait variables. After multivariable adjustment, participants in the lowest bicarbonate tertile (< 25 mEq/L) had 8.6 cm/s slower speed (95% confidence interval [CI] 3.2-13.9), 7.9 cm shorter stride length (95% CI 3.5-12.2), and 0.03 s longer double support time (95% CI 0.002-0.1) compared with those in the middle tertile (25-27 mEq/L). Furthermore, lower bicarbonate levels were associated with more severe gait abnormalities in a graded manner. After further adjustment for possible mediating factors, associations were attenuated but remained significant. Among participants with CKD, associations were of similar or greater magnitude compared with those without CKD. Factor analysis was performed to synthesize the individual gait variables into unifying domains: among the pace, rhythm, and variability domains, lower serum bicarbonate was associated with worse performance in pace. In sum, lower serum bicarbonate was independently associated with worse performance on several quantitative measures of gait among older adults.

Clinical Consequences of Metabolic Acidosis-Muscle.

Metabolic acidosis is common in people with chronic kidney disease and can contribute to functional decline, morbidity, and mortality. One avenue through which metabolic acidosis can result in these adverse clinical outcomes is by negatively impacting skeletal muscle; this can occur through several pathways. First, metabolic acidosis promotes protein degradation and impairs protein synthesis, which lead to muscle breakdown. Second, metabolic acidosis hinders mitochondrial function, which decreases oxidative phosphorylation and reduces energy production. Third, metabolic acidosis directly limits muscle contraction. The purpose of this review is to examine the specific mechanisms of each pathway through which metabolic acidosis affects muscle, the impact of metabolic acidosis on physical function, and the effect of treating metabolic acidosis on functional outcomes.

COVID-19 and Preexisting Comorbidities: Risks, Synergies, and Clinical Outcomes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated symptoms, named coronavirus disease 2019 (COVID-19), have rapidly spread worldwide, resulting in the declaration of a pandemic. When several countries began enacting quarantine and lockdown policies, the pandemic as it is now known truly began. While most patients have minimal symptoms, approximately 20% of verified subjects are suffering from serious medical consequences. Co-existing diseases, such as cardiovascular disease, cancer, diabetes, and others, have been shown to make patients more vulnerable to severe outcomes from COVID-19 by modulating host-viral interactions and immune responses, causing severe infection and mortality. In this review, we outline the putative signaling pathways at the interface of COVID-19 and several diseases, emphasizing the clinical and molecular implications of concurring diseases in COVID-19 clinical outcomes. As evidence is limited on co-existing diseases and COVID-19, most findings are preliminary, and further research is required for optimal management of patients with comorbidities.

Long-Term Immunity and Antibody Response: Challenges for Developing Efficient COVID-19 Vaccines.

Questions and concerns regarding the efficacy and immunogenicity of coronavirus disease 2019 (COVID-19) vaccines have plagued scientists since the BNT162b2 mRNA vaccine was introduced in late 2020. As a result, decisions about vaccine boosters based on breakthrough infection rates and the decline of antibody titers have commanded worldwide attention and research. COVID-19 patients have displayed continued severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-spike-protein-specific antibodies and neutralizing antibodies in longitudinal studies; in addition, cytokine activation has been detected at early steps following SARS-CoV-2 infection. Epitopes that are highly reactive and can mediate long-term antibody responses have been identified at the spike and ORF1ab proteins. The N-terminal domain of the S1 and S2 subunits is the location of important SARS-CoV-2 spike protein epitopes. High sequence identity between earlier and newer variants of SARS-CoV-2 and different degrees of sequence homology among endemic human coronaviruses have been observed. Understanding the extent and duration of protective immunity is consequential for determining the course of the COVID-19 pandemic. Further knowledge of memory responses to different variants of SARS-CoV-2 is needed to improve the design of the vaccine.

Effect of growth media and washing on the spectral signatures of aerosolized biological simulants.

We have evaluated the influence of growth media and washing on the laser-induced fluorescence spectra of bacteria. Three different bacterial simulants were cultured in three types of growth media. Three kinds of samples were generated from each culture: the culture itself, the growth medium alone, and a triple-washed sample. The materials were injected as aerosols in a lab-sized lidar aerosol chamber to obtain their spectra. Using two different analysis approaches, signature variations were observed between the three kinds of samples for most combinations of growth media/bacteria. This study concludes that the culture media used influences the spectral signatures.

Anthrax letters: personal exposure, building contamination, and effectiveness of immediate mitigation measures.

This report is the first detailed and quantitative study of potential mitigation procedures intended to deal with anthrax letters using a simulated anthrax letter release within an actual office building. Spore aerosols were created by opening letters containing 0.1 g of dry powdered Bacillus atrophaeus spores. Culturable aerosol samples were collected using slit-to-agar and filter-based samplers. Five test scenarios were designed to determine whether simple mitigation procedures or activities carried out by the person who opened the letter made a significant difference to aerosol concentrations in comparison to a control scenario where no activity took place. Surface contamination of the letter opener was measured at 10 body points for Scenarios 1 to 4. A sixth scenario, based on published Centers for Disease Control and Prevention anthrax letter response guidelines, used letters containing 1 g of spores. Results demonstrated that the spore aerosol spread throughout the building in less than 4.5 min. Potential mitigation techniques such as closing the office door or shutting off the ventilation system were not effective. Activities carried out by the letter opener including moving, walking to another location, and spraying water onto the contaminated desk with a hand sprayer all resulted in significantly higher aerosol concentrations in comparison to control. The potential total inhalational hazard for the letter opener during the five test scenarios ranged from 4.1 x 10(5) to 1.6 x 10(6) colony forming units (CFU) compared to 3.9 x 10(5) CFU for the control. Surface contamination of the letter opener (Scenarios 1 to 4) was highest on the right hip (4.8 x 10(4) to 1.0 x 10(5) CFU/cm(- 2)) and lowest on the right or left side of the head (2.2 x 10(2) to 3.7 x 10(3) CFU/cm(-2)). The statistically based methodology used in this study provided the means to objectively assess anthrax letter protocols to determine their effectiveness under realistic conditions. Potential mitigation procedures tested in this study did not reduce aerosol hazard or surface contamination.

Walking while Talking in Older Adults with Chronic Kidney Disease.

BACKGROUND AND OBJECTIVES: Walking while talking is a dual cognitive-motor task that predicts frailty, falls, and cognitive decline in the general elderly population. Adults with CKD have gait abnormalities during usual walking. It is unknown whether they have greater gait abnormalities and cognitive-motor interference during walking while talking. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Community-dwelling, nondisabled adults (n=330) ≥65 years of age underwent quantitative gait analysis, including walking while talking. Differences in walking-while-talking performance by CKD status were evaluated, and relative changes between walking-while-talking and walking alone performance were computed to quantify cognitive-motor interference (dual-task cost). Associations were tested using multivariable linear spline regression models, and independent gait domains were derived using factor analysis. CKD was defined as an eGFR<60 ml/min per 1.73 m2. RESULTS: CKD was present in 134 (41%) participants. Participants with CKD had slower gait speed along with various gait cycle abnormalities during walking while talking: among those with CKD, every 10-ml/min per 1.73 m2 lower eGFR was associated with 3.3-cm/s (95% confidence interval, 0.4 to 6.1) slower gait speed, 1.8-cm (95% confidence interval, 0.6 to 3.0) shorter step length, 1.1% (95% confidence interval, 0.6 to 1.7) less time in the swing phase, and 1.4% (95% confidence interval, 0.5 to 2.3) greater time in double support after multivariable adjustment. When comparing walking while talking with walking alone, every 10-ml/min per 1.73 m2 lower eGFR was associated with 1.8% (95% confidence interval, 0.5 to 3.2) greater decrease in time in the swing phase and 0.9% (95% confidence interval, 0.2 to 1.5) greater increase in time in the stance phase. Factor analysis identified three walking-while-talking domains and three dual-task cost domains: eGFR was associated specifically with the rhythm domain for both walking-while-talking and dual-task cost. Every 10-ml/min per 1.73 m2 lower eGFR was associated with a poorer performance of 0.2 SD (95% confidence interval, 0.1 to 0.3) for walking while talking and 0.2 SD (95% confidence interval, 0.03 to 0.3) for dual-task cost. CONCLUSIONS: During walking while talking, CKD is associated with gait abnormalities, possibly due to increased cognitive-motor interference.

Pulmonary deposition of aerosolized Bacillus atrophaeus in a Swine model due to exposure from a simulated anthrax letter incident.

Dry anthrax spore powder is readily disseminated as an aerosol and it is possible that passive dispersion when opening a letter containing anthrax spores may result in lethal doses to humans. The specific aim of this study was to quantify the respirable aerosol hazard associated with opening an envelope/letter contaminated with a dry spore powder of the biological pathogen anthrax in a typical office environment. An envelope containing a letter contaminated with 1.0 g of dry Bacillus atrophaeus (BG) spores (pathogen simulant) was opened in the presence of an unrestrained swine model. Aerosolized spores were detected in the room in seconds and peak concentrations occurred by three minutes. The swine, located approximately 1.5 m from the source, was exposed to the aerosol for 28 min following the letter opening event and then moved to a clean room for 30 min. A necropsy was completed to determine the extent of in vivo spore deposition in the lungs. The median number of viable colony forming units (CFU) measured in the combined right and left lung was 21,200: the average mass of both lungs was 283 g. In excess of 100 CFU per gram of lung tissue was found at sites within the anterior, intermediate and posterior lobes. The results of this study confirmed that opening an envelope containing spores generated an aerosol spanning the respirable particle size range of 1-10 microm, and that normal respiration of swine led to spore deposition throughout the lungs. The observed deposition of spores in the lungs of the swine is within the LD(50) range of 2,500-55,000 estimated for humans for inhaled anthrax. Thus, there would appear to be a significant health risk to those individuals exposed to anthrax spores when opening a contaminated envelope.

Immunoengineering in glioblastoma imaging and therapy.

Patients diagnosed with glioblastoma have poor prognosis. Conventional treatment strategies such as surgery, chemotherapy, and radiation therapy demonstrated limited clinical success and have considerable side effects on healthy tissues. A central challenge in treating brain tumors is the poor permeability of the blood-brain barrier (BBB) to therapeutics. Recently, various methods based on immunotherapy and nanotechnology have demonstrated potential in addressing these obstacles by enabling precise targeting of brain tumors to minimize adverse effects, while increasing targeted drug delivery across the BBB. In addition to treating the tumors, these approaches may be used in conjunction with imaging modalities, such as magnetic resonance imaging and positron emission tomography to enhance the prognosis procedures. This review aims to provide mechanistic understanding of immune system regulation in the central nervous system and the benefits of nanoparticles in the prognosis of brain tumors. This article is characterized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Cells at the Nanoscale Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.