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Oxygen deprivation and excess are both toxic. Thus, the bodys ability to adapt to varying oxygen tensions is critical for survival. While the hypoxia transcriptional response has been well studied, the post-translational effects of oxygen have been underexplored. In this study, we systematically investigate protein turnover rates in mouse heart, lung, and brain under different inhaled oxygen tensions. We find that the lung proteome is the most responsive to varying oxygen tensions. In particular, several extracellular matrix (ECM) proteins are stabilized in the lung under both hypoxia and hyperoxia. Furthermore, we show that complex 1 of the electron transport chain is destabilized in hyperoxia, in accordance with the exacerbation of associated disease models by hyperoxia and rescue by hypoxia. Moreover, we nominate MYBBP1A as a hyperoxia transcriptional regulator, particularly in the context of rRNA homeostasis. Overall, our study highlights the importance of varying oxygen tensions on protein turnover rates and identifies tissue-specific mediators of oxygen-dependent responses.

Abstract Introduction Identifying clinical factors that increase the risk of mortality in COVID-19 patients is crucial. This enables targeted screening, optimizing treatment, and prevention of severe complications, ultimately reducing death rates. This study aimed to develop prediction models for the death of patients (i.e., survival or death) during the COVID-19 pandemic in Shiraz, exploring the main influencing factors. Method We conducted a retrospective cohort study using hospital-based records of 1030 individuals diagnosed with COVID-19, who were hospitalized for treatment between March 21, 2021, and March 21, 2022, in Shiraz, Iran. Variables related to the final outcome were selected based on criteria and univariate logistic regression. Hierarchical multiple logistic regression and classification and regression tree (CART) models were utilized to explore the relationships between potential influencing factors and the final outcome. Additionally, methods were employed to identify the high-risk population for increased mortality rates during COVID-19. Finally, accuracy was evaluated the performance of the models, with the area under the receiver operator characteristic curve(AUC), sensitivity, and specificity metrics. Results In this study, 558 (54.2%) individuals infected with COVID-19 died. The final model showed that the type of medicine antiviral (OR: 11.10, p = 0.038) than reference (antiviral and corticosteroid), and discharge oxygen saturation(O2) (OR: 1.10, p

Abstract Sleep disorders can adversely affect physical, sexual, and marital health, particularly among middle-aged women. This study aimed to determine the relationship between sleep quality and marital satisfaction of working women during the premenopausal period. In this cross-sectional study, we selected 150 women working at Shiraz University of Medical Sciences in Iran was selected using random cluster sampling. A demographic information form, the Pittsburgh Sleep Quality Index (PSQI), and the Evaluation and Nurturing Relationship Issues, Communication, and Happiness (ENRICH) marital satisfaction scale were used for data collection. The Data were analyzed using SPSS.22 software at a significance level of P

Abstract Objective Otitis media with effusion is common in children with cleft palates. This study aimed to investigate the link between palatal closure techniques and audiological outcomes. Methods In this retrospective‐prospective cohort study, we examined the relationship between palate repair techniques and hearing outcomes in children with cleft palates. From 2017 to 2022, 190 ears of 95 cleft patients were studied at the Cleft Lip and Palate Department of Shiraz University of Medical Sciences. Variables assessed included the surgical technique, cleft severity, auditory brainstem response (ABR) threshold, and tympanometry configuration. Results The mean ABR improved from a prepalatoplasty value of 39.51(11.62) decibels (dB) to a postpalatoplasty mean of 26.61(11.60) dB (Cohen's d: 1.12 [95% CI; 0.90–1.34]). Initially, 87.9% of the studied ears exhibited abnormal tympanometry, but this significantly decreased to 47% postsurgery (risk ratio: 4.43 [95% CI; 1.20–16.43]). When compared with Sommerlad intravelar veloplasty, the Nadjmi modified Furlow palatoplasty was associated with a notably lower mean ABR (β: −6.58 [95% CI: −10.43 to −2.73], p‐value = .001) and a reduced frequency of abnormal tympanometry (odds ratio [OR]: −1.10; 95% CI: −1.85 to −0.36, p‐value = .004). Factors like prepalatoplasty ABR, cleft palate severity, gender, and syndromic did not confound these findings. Conclusions Although the Nadjmi modified Furlow palatoplasty showed better results, our findings indicate a significant improvement in ABR and tympanometry outcomes for both techniques. Future randomized controlled trials are suggested to confirm the influence of palatal closure techniques on audiological outcomes. Level of Evidence 3b.

Abstract A key goal for implanted medical devices is that they do not elicit a detrimental immune response. Macrophages play critical roles in the modulation of the host immune response and are the cells responsible for persistent inflammatory reactions to implanted biomaterials. Two novel immune‐instructive polymers that stimulate pro‐ or anti‐inflammatory responses from macrophages in vitro are investigated. These also modulate in vivo foreign body responses (FBR) when implanted subcutaneously in mice. Immunofluorescent staining of tissue abutting the polymer reveals responses consistent with pro‐ or anti‐inflammatory responses previously described for these polymers. Three Dimensional OrbiTrap Secondary Ion Mass Spectrometry (3D OrbiSIMS) analysis to spatially characterize the metabolites in the tissue surrounding the implant, providing molecular histology insight into the metabolite response in the host is applied. For the pro‐inflammatory polymer, monoacylglycerols (MG) and diacylglycerols (DG) are observed at increased intensity, while for the anti‐inflammatory coating, the number of phospholipid species detected decreased, and pyridine and pyrimidine levels are elevated. Small molecule signatures from single‐cell studies of M2 macrophages in vitro correlate with the in vivo observations, suggesting potential for prediction. Metabolite characterization by the 3D OrbiSIMS is shown to provide insight into the mechanism of bio‐instructive materials as medical devices and to inform on the FBR to biomaterials.

Background & Aims Some studies have reported a high risk of metabolic syndrome among women and night shift workers. This study aims to determine the status of metabolic syndrome laboratory indicators and thyroid function tests in nurses working in Rajaei Cardiovascular, Medical, & Research Center (RCMRC) in Tehran, Iran, in 2020-2021. Materials & Methods This is a descriptive cross-sectional study on the health records of nurses working in RCMRC. The sampling was done using a census method. Records with incomplete information were excluded. A form containing demographic characteristics, thyroid function indicators, and metabolic syndrome laboratory indicators was used to collect data from the health records. Data analysis was performed in SPSS software, version 26. Results Out of 401 reviewed records, 339 cases (84.5%) were for female nurses. The mean age of nurses was 37.47±8.68 years, and their mean work experience was 13.17±8.07 years. According to the criteria of the American Heart Association and the National Heart, Lung, and Blood Institute, the prevalence of abnormalities in metabolic syndrome laboratory tests was 5.21%, while according to the National Cholesterol Education Program III criteria, it was 2.99%. The prevalence of clinical hypothyroidism was 0.2%; subclinical hypothyroidism, 12.0%; and subclinical hyperthyroidism, 1.5%. Conclusion The prevalence of metabolic syndrome and thyroid disorders among nurses working in RCMRC is not considerable. Further large-scale studies (cohort or longitudinal) are recommended.

Abstract Background The aim of the current study is to assess the prevalence of different categories of thyroid dysfunction and their associated risk factors among the modern urban population of Tehran, the capital of Iran. Methods The present investigation is a sub-study of the HAMRAH study, a population-based prospective study designed to assess the prevalence of traditional cardiovascular risk factors and their changes through a 10-year follow-up. 2228 (61% female) adults aged between 30 and 75 years old and with no overt cardiovascular diseases were selected through a multistage cluster randomized sampling. Blood levels of thyroid-stimulating hormone (TSH), thyroxin (T4), and triiodothyronine (T3) were measured with the aim of assessing the prevalence of abnormal thyroid function status among the modern urban Iranian population, and in order to report the total prevalence of participants with clinical hypo- or hyperthyroidism, the number of individuals taking thyroid-related drugs were added to the ones with overt thyroid dysfunction. A subgroup analysis was also performed to determine the associated risk factors of thyroid dysfunction. Results The prevalence of thyroid dysfunction among the total population was 7% (95%CI: 5.9 − 8%) and 0.4% (95% CI: 0.1 − 0.6%) for subclinical and overt hypothyroidism, and 1.6% (95% CI: 1 − 2%) and 0.2% (95% CI: 0 − 0.3%) for subclinical and overt hyperthyroidism, respectively. Clinical thyroid dysfunction was detected in 10.3% of the study population (9.4% had clinical hypo- and 0.9% had clinical hyperthyroidism). In the subgroup analysis, thyroid dysfunction was significantly more prevalent among the female participants (P-value = 0.029). Conclusions In the current study, the prevalence of different categories of abnormal thyroid status, and also the rate of clinical hypo- and hyperthyroidism was assessed using the data collected from the first phase of the HAMRAH Study. In this study, we detected a higher prevalence of clinical and subclinical hypothyroidism among the Iranian population compared to the previous studies.

Liver fibrosis is a complex, dynamic process associated with a broad spectrum of chronic liver diseases and acute liver failure, characterised by the dysregulated intrahepatic production of extracellular matrix proteins replacing functional liver cells with scar tissue. Fibrosis progresses due to an interrelated cycle of hepatocellular injury, triggering a persistent wound-healing response. The accumulation of scar tissue and chronic inflammation can eventually lead to cirrhosis and hepatocellular carcinoma. Currently, no therapies exist to directly treat or reverse liver fibrosis; hence, it remains a substantial global disease burden. A better understanding of the intricate inflammatory network that drives the initiation and maintenance of liver fibrosis to enable the rationale design of new intervention strategies is required. This review clarifies the most current understanding of the hepatic fibrosis cellular network with a focus on the role of regulatory T cells, and a possible trajectory for T cell immunotherapy in fibrosis treatment. Despite good progress in elucidating the role of the immune system in liver fibrosis, future work to better define the function of different immune cells and their mediators at different fibrotic stages is needed, which will enhance the development of new therapies.

Abstract Introduction All businesses that deal directly with clients need to observe ethics, but in the nursing profession due to its nature, compliance with professional ethics becomes more necessary. On the other hand, nurses face tensions and difficult conditions in their daily work environment. Resilience is one of the most important abilities of human beings, which in difficult conditions causes effective adaptation to stress-causing factors. Therefore, the relationship between resilience and professional ethics becomes important. The aim of the study The present study was conducted to investigate the relationship between resilience and professional ethics in nurses of Shahid Ganji Hospital, Borazjan 2022–2023. Methods The current study is a cross-sectional descriptive-analytical study. The study environment was Shahid Ganji Hospital in Borazjan, Bushehr, Iran. The research method of the current study was census, so all 400 nurses of this hospital were invited to participate in the study. Finally, 340 of them were included in the study based on the inclusion criteria. Data collection tools included a demographic information form, Connor-Davidson questionnaire, and Cadozier professional ethics questionnaire. Data analysis was done using SPSS version 22 software. Results Most of the participants were between 25 and 30 years old. The average overall score of resilience and professional ethics of nurses participating in the study was 64.1 ± 16.3 and 34.3 ± 9.4, respectively. No significant difference was observed between the demographic characteristics of nurses with resilience and professional ethics. The Spearman correlation coefficient indicated a statistically significant and inverse relationship between professional ethics and resilience levels (r = -0.265, P

Tissue regeneration and remodeling involve many complex stages. Macrophages are critical in maintaining micro-environmental homeostasis by regulating inflammation and orchestrating wound healing. They display high plasticity in response to various stimuli, showing a spectrum of functional phenotypes that vary from M1 (pro-inflammatory) to M2 (anti-inflammatory) macrophages. While transient inflammation is an essential trigger for tissue healing following an injury, sustained inflammation (e.g., in foreign body response to implants, diabetes or inflammatory diseases) can hinder tissue healing and cause tissue damage. Modulating macrophage polarization has emerged as an effective strategy for enhancing immune-mediated tissue regeneration and promoting better integration of implantable materials in the host. This article provides an overview of macrophages’ functional properties followed by discussing different strategies for modulating macrophage polarization. Advances in the use of synthetic and natural biomaterials to fabricate immune-modulatory materials are highlighted. This reveals that the development and clinical application of more effective immunomodulatory systems targeting macrophage polarization under pathological conditions will be driven by a detailed understanding of the factors that regulate macrophage polarization and biological function in order to optimize existing methods and generate novel strategies to control cell phenotype.

Biomaterials are designed to interact with biological systems to replace, support, enhance, or monitor their function. However, there are challenges associated with traditional biomaterials’ development due to the lack of underlying theory governing cell response to materials’ chemistry. This leads to the time-consuming process of testing different materials plus the adverse reactions in the body such as cytotoxicity and foreign body response. High-throughput screening (HTS) offers a solution to these challenges by enabling rapid and simultaneous testing of a large number of materials to determine their bio-interactions and biocompatibility. Secreted proteins regulate many physiological functions and determine the success of implanted biomaterials through directing cell behaviour. However, the majority of biomaterials’ HTS platforms are suitable for microscopic analyses of cell behaviour and not for investigating non-adherent cells or measuring cell secretions. Here, we describe a multi-well platform adaptable to robotic printing of polymers and suitable for secretome profiling of both adherent and non-adherent cells. We detail the platform's development steps, encompassing the preparation of individual cell culture chambers, polymer printing, and the culture environment, as well as examples to demonstrate surface chemical characterisation and biological assessments of secreted mediators. Such platforms will no doubt facilitate the discovery of novel biomaterials and broaden their scope by adapting wider arrays of cell types and incorporating assessments of both secretome and cell-bound interactions.Key features• Detailed protocols for preparation of substrate for contact printing of acrylate-based polymers including O2 plasma etching, functionalisation process, and Poly(2-hydroxyethyl methacrylate) (pHEMA) dip coating.• Preparations of 7 mm × 7 mm polymers employing pin printing system.• Provision of confined area for each polymer using ProPlate® multi-well chambers.• Compatibility of this platform was validated using adherent cells [primary human monocyte–derived macrophages (MDMs)) and non-adherent cells (primary human monocyte–derived dendritic cells (moDCs)].• Examples of the adaptability of the platform for secretome analysis including five different cytokines using enzyme-linked immunosorbent assay (ELISA, DuoSet®).Graphical overview

The current research was conducted to determine the aflatoxigenic and non-aflatoxigenic Aspergillus flavus isolates and the frequency of aflatoxin levels (B1, B2, G1, G2), in main feed ingredients (corn and soybean meal) and poultry finished feed (in mash and pellet forms). Eighty-five samples of corn, soybean meal, and poultry finished feed was randomly collected from feed mills in Iran. Regarding macro and microscopic morphological criteria, Aspergillus isolates were identified, and aflatoxins were determined by thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC). All of poultry feed samples were contaminated with different levels of aflatoxins, ranging from ND (they were not detected in those samples) to 5.58 µg/kg. At all stages of processing, the poultry feed had lower levels of aflatoxins in comparison with the accepted/residue levels of poultry feed mills. Higher amounts of aflatoxins (B1, B2, G1, G2, and total) were detected in pelleted feed, compared to other poultry samples (P < 0.05). The total toxin level in mash feed samples reached a maximum of 3.31 ppb. The results indicate that finished feed samples in pellet form may pose a greater risk than their individual ingredients in poultry feed, particularly when suboptimal conditions exist for eliminating fungal populations. So, the prevention and reduction of (Aspergillus section Flavi) are highly important in maintaining quality control of poultry feed, as the production of aflatoxins can occur during the process of converting raw ingredients into finished feed.

Abstract Objective This study aimed to evaluate the inflammatory effect of diet using the dietary Inflammatory Index (DII) on the odds of periodontitis. We hypothesized that a diet with high DII scores (a pro-inflammatory diet) is associated with high chronic and systematic inflammation resulting in periodontitis. Periodontitis is one of the most common inflammatory diseases that affect the tissues around the tooth and results from the interaction of bacterial infection and the host immune response. The DII shows the association between different food components and the level of specific inflammatory biomarkers. Method The food intake of 87 cases with diagnosed periodontitis and 87 control was assessed using a 163-item valid food frequency questionnaire (FFQ). The DII was calculated based on the FFQ data. Logistic and linear regression models adjusting for multivariable confounders were used to investigate the odds ratio (OR) and 95% confidence intervals (CI) of developing periodontitis. Results There was a significant difference between the mean intake of micronutrients and food groups, including saturated fatty acids (SFAs), iron, magnesium, manganese, vitamin C, crude fiber, selenium, chromium, whole fiber, caffeine, dairy, and meat, between patients with periodontitis and the control group (p-value˂0.05). DII scores in this study ranged from -3.13 to + 0.99. However, the periodontitis OR in the raw and multivariable-adjusted models was not statistically significant (multivariable-adjusted OR tertiles 1 vs. tertiles 3 = 2.00, 95%CI: 0.4–90.42, p-value = 0.08). A similar result was also observed in the continuous model of DII (multivariable-adjusted OR DII continuous = 1.93, 95%CI: 0.30–98.79, p-value = 0.05). Conclusion Although the OR was not statistically significant in crude models, a significant trend was found in multivariable-adjusted models. The results were promising since this is the first study to examine the association between diet-induced inflammation and dental disease. It is advisable to conduct additional studies with high sample sizes and other designs, such as prospective studies.

Background: Hysterosalpingography is a vital diagnostic method for identifying anatomical causes of infertility, often used as a cost-effective screening test. This study aimed to investigate hysterosalpingography results in infertile women.Methods: A quantitative, descriptive, and analytic cross-sectional study was conducted on 180 infertile couples referred to Ghadir Maternal and Child Hospital in Shiraz, Iran between February and July 2015-2016. Data were collected from patient records and hysterosalpingography findings. A questionnaire encompassing demographic information and hysterosalpingography results was utilized. Qualitative and quantitative variables were described using frequency and mean± standard deviation. Data were analyzed using Kolmogorov-Smirnov normality test, Chi-square, and generalized linear models via IBM SPSS version 22.Results: Hysterosalpingography (HSG) revealed that 145 women (80.6%) exhibited normal uterine and tubal findings, while 35 women (19.4%) displayed abnormal results (classified as normal and abnormal HSG findings). Women with abnormal hysterosalpingography were observed to have a higher likelihood of primary infertility (OR=3.8, 95%CI (1.427-10.10), P=0.008). Furthermore, the study assessed the impact of Body Mass Index (BMI) and identified that women in the abnormal HSG group had a higher body mass index (OR=0.89, 95%CI (0.794-0.992), P=0.035).Conclusions: Tubal adhesion stemming from undiagnosed and untreated sexual infections can lead to primary infertility. Limited resources may hinder timely detection and treatment access, exacerbating the issue. The correlation between obesity and infertility could be attributed to an unhealthy lifestyle in low-income families. Encouraging health education within low to middle-income communities is recommended to prevent sexually transmitted infections and promote healthier lifestyles, ultimately reducing the incidence of primary infertility.

Abstract Background The COVID-19 pandemic has led to exceptional stress in pregnant women. The aim of the present study was to investigate associations of maternal stress (pandemic-related and -unrelated), anxiety, and relationship satisfaction experienced during the COVID-19 pandemic with prenatal mother-infant attachment. Methods An online study was conducted evaluating pandemic-related stress, pregnancy-specific stress (unrelated to the pandemic), anxiety, partnership satisfaction, and maternal-fetal attachment in German-speaking women during the second COVID-19 lockdown between January and March 2021. In total, 431 pregnant women (349 lived in Germany and 82 in Switzerland) filled in the questionnaires and gave information on demographic and pregnancy-related variables (i.e. age, gestational age, parity). Bivariate correlations were calculated in order to investigate associations between the different variables and additionally, a hierarchical regression model was conducted in order to evaluate the influence of the independent variables on prenatal attachment. Results The hierarchical regression analysis revealed that after controlling for age, gestational age, and parity higher pandemic-related stress, namely stress associated with feeling unprepared for birth, higher partnership satisfaction as well as higher positive appraisal (considered as a way of coping with pandemic-related stress) was associated with stronger maternal-fetal attachment, whereas associations of anxiety and other forms of stress were non-significant. Conclusions The study highlights interesting associations between maternal pandemic-related preparedness stress and positive appraisal of the pregnancy as well as partnership satisfaction and prenatal attachment in women pregnant during the COVID-19 pandemic.

Key Clinical Message In patients presenting with aortic ectasia and myxomatous valve diseases at young ages, possible underlying acromegaly should be in mind. Abstract Acromegaly is a chronic systemic disease mainly caused by the benign pituitary adenoma secreting growth hormone (GH) in excess. Acromegaly is associated with various complications such as cardiovascular diseases. In this regard, timely diagnosis, and management of these patients could be life‐saving. Herein, a case of aneurysmal dilation of the sinus of Valsalva with severe aortic and mitral regurgitation in a patient with undiagnosed acromegaly is presented.

Background: The status of care in the preconception and pregnancy periods in women who use substances can have an impact on maternal and neonatal health. This study aimed to assess the provision of preconception care, prenatal care, and postnatal mother-to-child bonding among pregnant women who use substances. Methods: An ambidirectional cohort study was conducted, involving 69 pregnant women who reported substance use and had it confirmed using a ten-parameter panel kit (M10T) manufactured by Hannan Teb Pars Company. These women were selected from a referral maternity hospital between January and December 2020, using a convenience sampling method. Sociodemographic information, obstetric and medical history, and information about preconception and prenatal care were collected. All maternal and neonatal outcomes were recorded from the time of admission to the time of discharge for both the mothers and their neonates. Neonatal abstinence syndrome and mother-to-child bonding were assessed using modified Finnegan's neonatal abstinence tool and a postpartum bonding questionnaire, respectively. The data were analyzed using descriptive and inferential tests using SPSS software version 22. Result: The mean age of the women was 32.8 ± 5.7 years. The mean duration of substance use was 5.1 ± 3.5 years. 48% of the pregnancies were reported as unwanted. A total of 94.2% and 50.7% of pregnant women did not receive preconception care and prenatal care, respectively. There was no association between pregnancy wantedness and receiving preconception care (P = 0.287), but a significant association was observed for prenatal care (P

Jessel et al. ("Behavior Analysis & Practice," 13(1), 205-216, 2020a) conducted a review of the functional analysis literature between the years 1965 and 2016. The authors found an increasing trend in analyses replicating the components of Iwata et al. ("Journal of Applied Behavior Analysis," 27, 197-209, 1982/1994a) and determined that those components have come to represent a standard format. Since the inception of the standard, other functional analysis formats (e.g., brief, latency-based, trial-based) have been developed to improve analysis efficiency and control, with most retaining fundamental components of the standard and some omitting all (e.g., interview-informed, synthesized contingency analysis; IISCA). We conducted a review of functional analyses in this two-part evaluation to determine the levels of efficiency and control afforded by functional analysis variations and formats.

Background: One of the factors effective in controlling acute coronary syndrome (ACS) symptoms, such as heart failure, is sufficient knowledge of the disease, factors effective on its occurrence, and its prevention. Moreover, the improvement of self-efficacy, which is a predictor of important life factors in these patients, such as treatment process and quality of life (QOL), must be considered as one of the main goals of nursing care for these patients. The aim of this study was to determine the effect of the family-centered self-care program on the health literacy level and self-efficacy of patients with ACS during hospital discharge. Materials and Methods: The present study was a quasi-experimental study performed with a pretest-posttest design. The statistical population of the study consisted of all patients with ACS hospitalized at Shahid Chamran Hospital in Isfahan in 2020. Through the convenience sampling method, 50 patients were selected and randomly divided into intervention and control groups. For the intervention group, 6 sessions of 45–60 minutes of family-centered self-care intervention were held. The subjects completed the Health Literacy for Iranian Adults (HELIA) questionnaire before and after the intervention. Data were analyzed using Chi-square test, independent t-test, and paired t-test in the SPSS statistical software. Results: The mean score of health literacy did not significantly differ between the intervention and control groups before the intervention (p > 0.050). However, after the intervention, this rate was equal to 82.16 (7.94) and 60.85 (15.71) in the intervention and control groups, respectively, which was significantly higher in the intervention group compared to the control group (p < 0.001). Furthermore, there was no significant difference between the two groups in terms of the mean self-efficacy score before the intervention (p > 0.05). However, after the intervention, this score was significantly higher in the intervention group 34.71 (10.11) compared to the control group 35.22 (13.30). Conclusions: Family-centered self-care program after discharge, as a simple, applicable, and efficient method can improve the health literacy level and self-efficacy of patients with ACS.

The Three-dimensional OrbiTrap Secondary Ion Mass Spectrometry (3D OrbiSIMS) is a secondary ion mass spectrometry instrument, a combination of a Time of Flight (ToF) instrument with an Orbitrap analyzer. The 3D OrbiSIMS technique is a powerful tool for metabolic profiling in biological samples. This can be achieved at subcellular spatial resolution, high sensitivity, and high mass-resolving power coupled with MS/MS analysis. Characterizing the metabolic signature of macrophage subsets within tissue sections offers great potential to understand the response of the human immune system to implanted biomaterials. Here, we describe a protocol for direct analysis of individual cells after in vitro differentiation of naïve monocytes into M1 and M2 phenotypes using cytokines. As a first step in vivo, we investigate explanted silicon catheter sections as a medical device in a rodent model of foreign body response. Protocols are presented to allow the host response to different immune instructive materials to be compared. The first demonstration of this capability illustrates the great potential of direct cell and tissue section analysis for in situ metabolite profiling to probe functional phenotypes using molecular signatures. Details of the in vitro cell approach, materials, sample preparation, and explant handling are presented, in addition to the data acquisition approaches and the data analysis pipelines required to achieve useful interpretation of these complex spectra. This method is useful for in situ characterization of both in vitro single cells and ex vivo tissue sections. This will aid the understanding of the immune response to medical implants by informing the design of immune-instructive biomaterials with positive interactions. It can also be used to investigate a broad range of other clinically relevant therapeutics and immune dysregulations.Graphical overview

Abstract Immunity to previously encountered viruses can alter response to unrelated pathogens. We reasoned that similar mechanism may also involve SARS-CoV-2 and thereby affect the specificity and the quality of the immune response against the virus. Here, we employed high-throughput next generation phage display method to explore the link between antibody immune response to previously encountered antigens and spike (S) glycoprotein. By profiling the antibody response in COVID-19 naïve individuals with a diverse clinical history (including cardiovascular, neurological, or oncological diseases), we identified 15 highly antigenic epitopes on spike protein that showed cross-reactivity with antigens of seasonal, persistent, latent or chronic infections from common human viruses. We observed varying degrees of cross-reactivity of different viral antigens with S in an epitope-specific manner. The data show that pre-existing SARS-CoV-2 S1 and S2 cross-reactive serum antibody is readily detectable in pre-pandemic cohort. In the severe COVID-19 cases, we found differential antibody response to the 15 defined antigenic and cross-reactive epitopes on spike. We also noted that despite the high mutation rates of Omicron (B.1.1.529) variants of SARS-CoV-2, some of the epitopes overlapped with the described mutations. Finally, we propose that the resolved epitopes on spike if targeted by re-called antibody response from SARS-CoV-2 infections or vaccinations can function in chronically ill COVID-19 naïve/unvaccinated individuals as immunogenic targets to boost antibodies augmenting the chronic conditions. Understanding the relationships between prior antigen exposure at the antibody epitope level and the immune response to subsequent infections with viruses from a different strain is paramount to guiding strategies to exit the COVID-19 pandemic.

Abstract The lifespans of proteins range from minutes to years within mammalian tissues. Protein lifespan is relevant to organismal aging, as long‐lived proteins accrue damage over time. It is unclear how protein lifetime is shaped by tissue context, where both cell turnover and proteolytic degradation contribute to protein turnover. We develop turnover and replication analysis by 15N isotope labeling (TRAIL) to quantify protein and cell lifetimes with high precision and demonstrate that cell turnover, sequence‐encoded features, and environmental factors modulate protein lifespan across tissues. Cell and protein turnover flux are comparable in proliferative tissues, while protein turnover outpaces cell turnover in slowly proliferative tissues. Physicochemical features such as hydrophobicity, charge, and disorder influence protein turnover in slowly proliferative tissues, but protein turnover is much less sequence‐selective in highly proliferative tissues. Protein lifetimes vary nonrandomly across tissues after correcting for cell turnover. Multiprotein complexes such as the ribosome have consistent lifetimes across tissues, while mitochondria, peroxisomes, and lipid droplets have variable lifetimes. TRAIL can be used to explore how environment, aging, and disease affect tissue homeostasis.

Bacterial contamination during space missions is problematic for human health and damages filters and other vital support systems. Staphylococcus aureus is both a human commensal and an opportunistic pathogen that colonizes human tissues and causes acute and chronic infections. Virulence and colonization factors are positively and negatively regulated, respectively, by bacterial cell-to-cell communication (quorum sensing) via the agr (accessory gene regulator) system. When cultured under low-shear modelled microgravity conditions (LSMMG), S. aureus has been reported to maintain a colonization rather than a pathogenic phenotype. Here, we show that the modulation of agr expression via reduced production of autoinducing peptide (AIP) signal molecules was responsible for this behavior. In an LSMMG environment, the S. aureus strains JE2 (methicillin-resistant) and SH1000 (methicillin-sensitive) both exhibited reduced cytotoxicity towards the human leukemia monocytic cell line (THP-1) and increased fibronectin binding. Using S. aureus agrP3::lux reporter gene fusions and mass spectrometry to quantify the AIP concentrations, the activation of agr, which depends on the binding of AIP to the transcriptional regulator AgrC, was delayed in the strains with an intact autoinducible agr system. This was because AIP production was reduced under these growth conditions compared with the ground controls. Under LSMMG, S. aureus agrP3::lux reporter strains that cannot produce endogenous AIPs still responded to exogenous AIPs. Provision of exogenous AIPs to S. aureus USA300 during microgravity culture restored the cytotoxicity of culture supernatants for the THP-1 cells. These data suggest that microgravity does not affect AgrC-AIP interactions but more likely the generation of AIPs.

A TEA-CO2 laser based DIAL is employed to determine the range resolved hexafluoride (SF6) concentration. An algorithm is developed here in favor of the lidar signal processing to improve the data assessment against the undesired ringing effect. The latter is known as a lidar waveform defect that arises from multiple reflections of transmission line during the data acquisition, detection and recording. Before retrieval of SF6 parameters, namely concentration and extinction coefficient, the noise removal is initially carried out by means of the wavelet thresholding. Then, the ringing effect is significantly suppressed according to the developed Gaussian decomposition method. Furthermore, the plume concentration is measured regarding the signal processing of the neighboring lines of the 32SF6 absorption band within the spectral range of 10.247–10.6 µm. The 32SF6 concentration is determined by improving the accuracy of the signal processing. The 3D visualization of the SF6 diffusion is carried out in time and distance domains through the lower troposphere too. Horizontal atmospheric extinction profiles are successively obtained based on the near boundary method (NBM) with the spatial resolution 3.75 m. Moreover, the extinction profiles are recorded in three typical meteorological conditions i.e. 2 × 10−4 m−1 (morning-still), 6 × 10−4 m−1 (afternoon-snow) and 7 × 10−4 m−1 (night-rainy). We have shown that developed Gaussian decomposition method certainly improves DIAL-data processing.

Functional communication training (FCT; Carr & Durand, 1985) is a common function-based treatment in which an alternative form of communication is taught to reduce problem behavior. FCT has been shown to result in substantial reductions of a variety of topographically and functionally different types of problem behavior in children and adults (efficacy). The extent to which these reductions maintain in relevant contexts and result in meaningful changes in the lives of those impacted (effectiveness) is the focus of this paper. This review evaluates the degree to which FCT has been established as an evidence-based practice in psychology (EBPP) according to the definition set out by the American Psychological Association's 2005 Presidential Task Force on Evidence-Based Practice. Our review finds overwhelming evidence in support of FCT as an efficacious treatment but highlights significant limitations in support of its effectiveness. In order to also be recognized as an EBPP, future research on FCT will need to focus more closely on issues related to home, school, and community application, feasibility, consumer satisfaction, and more general and global changes for the individual.

Abstract Background Domestication usually has negative effects on insect performance, especially when they are reared continuously for many generations. Rejuvenation can reduce the negative effects of domestication in the parasitoid, Trichogramma brassicae Bezdenko (Hymenoptera: Trichogrammatidae) reared for 30 generations (G) on Sitotroga cerealella (Olivier) (Lepidoptera: Gelechiidae). Life table and parasitism parameters in the primary colony (G31–G45) were compared with the respective colony rejuvenated with field-collected individuals. Results There were significant differences in life history traits between domesticated and rejuvenated populations. The highest (38.4 eggs/female) and lowest (13.3 eggs/female) fecundity was observed in rejuvenated G31 and domesticated G45, respectively. The highest values of the life table and parasitism parameters were observed in rejuvenated G31 without significant difference with G32, G33 and G34. The relationship between finite parasitism rate (ω) and generation number in both rejuvenated and domesticated populations were fitted to the cubic regression model, indicating the parasitism potential of T. brassicae increased significantly after adding feral individuals but decreased remarkably over the generations. Conclusions Therefore, it seems that adding 10% feral individuals re-established the reproductive performance of the wasps at least for four generations, and it needs to be repeated routinely or it needs to be made by adding a higher rate of feral individuals. However, this issue should be investigated by more studies in which different rates of feral individuals are added to the primary colony.

Rähni et al profile antibody response in patients with varied response to cancer immunotherapies. They identify antibody epitope responses that predict anti-cancer immunity elicited by immunotherapy.