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IntroductionAccumulating evidence indicates the importance of T cell immunity in vaccination-induced protection against severe COVID-19 disease, especially against SARS-CoV-2 Variants-of-Concern (VOCs) that more readily escape from recognition by neutralizing antibodies. However, there is limited knowledge on the T cell responses across different age groups and the impact of CMV status after primary and booster vaccination with different vaccine combinations. Moreover, it remains unclear whether age has an effect on the ability of T cells to cross-react against VOCs.MethodsTherefore, we interrogated the Spike-specific T cell responses in healthy adults of the Dutch population across different ages, whom received different vaccine types for the primary series and/or booster vaccination, using IFNɣ ELISpot. Cells were stimulated with overlapping peptide pools of the ancestral Spike protein and different VOCs.ResultsRobust Spike-specific T cell responses were detected in the vast majority of participants upon the primary vaccination series, regardless of the vaccine type (i.e. BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, or Ad26.COV2.S). Clearly, in the 70+ age group, responses were overall lower and showed more variation compared to younger age groups. Only in CMV-seropositive older adults (>70y) there was a significant inverse relation of age with T cell responses. Although T cell responses increased in all age groups after booster vaccination, Spike-specific T cell frequencies remained lower in the 70+ age group. Regardless of age or CMV status, primary mRNA-1273 vaccination followed by BNT162b2 booster vaccination showed limited booster effect compared to the BNT162b2/BNT162b2 or BNT162b2/mRNA-1273 primary-booster regimen. A modest reduction in cross-reactivity to the Alpha, Delta and Omicron BA.1, but not the Beta or Gamma variant, was observed after primary vaccination.DiscussionTogether, this study shows that age, CMV status, but also the primary-booster vaccination regimen influence the height of the vaccination-induced Spike-specific T cell response, but did not impact the VOC cross-reactivity.

The vasculature system is composed of a multiplicity of juxtaposed cells to generate a functional biological barrier between the blood and tissues. On the luminal surface of blood vessels, endothelial cells (ECs) are in close contact with circulating cells while supporting basal lamina and pericytes wrap the abluminal surface. Thus, the reciprocal interaction of pericytes with ECs is a vital element in the physiological activity of the vascular system. Several reports have indicated that the occurrence of pericyte dysfunction under ischemic and degenerative conditions results in varied micro and macro-vascular complications. Emerging evidence points to the fact that autophagy, a conserved self-digestive cell machinery, can regulate the activity of several cells like pericytes in response to various stresses and pathological conditions. Here, we aim to highlight the role of autophagic response in pericyte activity and angiogenesis potential following different pathological conditions.

Primary COVID-19 vaccination for children, 5-17 years of age, was offered in the Netherlands at a time when a substantial part of this population had already experienced a SARS-CoV-2 infection. While vaccination has been shown effective, underlying immune responses have not been extensively studied. We studied immune responsiveness to one and/or two doses of primary BNT162b2 mRNA vaccination and compared the humoral and cellular immune response in children with and without a preceding infection. Antibodies targeting the original SARS-CoV-2 Spike or Omicron Spike were measured by multiplex immunoassay. B-cell and T-cell responses were investigated using enzyme-linked immunosorbent spot (ELISpot) assays. The activation of CD4+ and CD8+ T cells was studied by flowcytometry. Primary vaccination induced both a humoral and cellular adaptive response in naive children. These responses were stronger in those with a history of infection prior to vaccination. A second vaccine dose did not further boost antibody levels in those who previously experienced an infection. Infection-induced responsiveness prior to vaccination was mainly detected in CD8+ T cells, while vaccine-induced T-cell responses were mostly by CD4+ T cells. Thus, SARS-CoV-2 infection prior to vaccination enhances adaptive cellular and humoral immune responses to primary COVID-19 vaccination in children. As most children are now expected to contract infection before the age of five, the impact of infection-induced immunity in children is of high relevance. Therefore, considering natural infection as a priming immunogen that enhances subsequent vaccine-responsiveness may help decision-making on the number and timing of vaccine doses.

BackgroundDietary micronutrients may play important roles in the improvement of the immune responses against SARS-CoV-2. This study aimed to assess the effect of micronutrients on platelet activating factor (PAF) and immunity with a special focus on the coronavirus disease 2019 (COVID-19).MethodsAll paper published in English on the effects of micronutrients including fat soluble vitamins, water soluble vitamins, and minerals on PAF, immunity, and COVID-19 were collected from online valid databases.ResultsVitamin A may modulate the expression of PAF-receptor gene in patients with COVID-19. Vitamin D may modulate inflammatory response through influencing PAF pathway. Vitamin E may improve COVID-19 related heart injuries by exert anti-PAF activities. Vitamin C status may have PAF related anti-inflammatory and micro-thrombotic effects in SARS-CoV-2 patients. Furthermore, some trace elements such as copper, selenium, and iron may have key roles in strengthens immunity by inactivate PAF acetyl hydrolase.ConclusionThis narrative review study highlighted the importance of micronutrients in the improvement of immune function through modulation of PAF in patients with COVID-19. Further longitudinal studies are warranted.

ObjectiveVarious studies have indicated the application of Coenzyme Q10 and probiotic bacteria such as Ligilactobacillus salivarius (L. salivarius) and Lactiplantibacillus plantarum (L. plantarum) in combating periodontal disease. Considering the positive effect of these two on oral health, and the destructive effect of S. mutans, in this study, we investigate the outcomes of the administration of probiotics and Q10 on infected HEp-2 cell viability and S. mutans adhesion in different settings.MethodsA 3-week-old human epidermoid laryngeal (HEp-2) cell line was cultured and exposed to two different probiotics and 3 different doses of Q10 doses. Samples were contaminated by S. mutans immediately (therapeutic setting) and after 3 hours (preventive setting). Eventually, the viability of HEp-2 cells was investigated by MTT. Also, the number of adhered S. mutans was explored by direct and indirect adhesion assays.ResultsL. plantarum and L. salivarius protect epithelial cells against S. mutans in both therapeutic and preventive settings, albeit not fully. In contrast, Q10 completely preserves the viability of infected Her HEp-2 cells at all concentrations. The effects of the coexistence of Q10 and probiotics were not quite equal, among which L. salivarius and 5 μg of Q10 form the best results. The microscopic adherence assay of S. mutans revealed that samples containing Q10 had significantly lower adhesion of probiotics and S. mutans to HEp-2 cells. Similarly, plates containing L. salivarius with 5μg or L. plantarum with 1μg Q10 or sole presence of L. salivarius had the lowest S. mutans adherence among others. Also, L. salivarius with 5μg Q10 had one of the highest probiotic adherences.ConclusionIn conclusion, co-administration of Q10 and probiotics especially in presence of L. salivarius with 5μg Q10 could have remarkable effects on HEp-2 cell viability, S. mutans, and probiotic adherence. Nevertheless, our study, for the first time, showed that Q10 might have an anti-bacterial activity by suppressing the adhesion of tested bacteria to HEp-2 cells. This hypothesis, if correct, suggests that due to their different mechanisms, co-prescription of Q10 and probiotics may lead to better clinical responses, especially in the mentiond dose.

Seabed morphology maps and data are critical for knowledge-building and best practice management of marine environments. To facilitate objective and repeatable production of these maps, we have developed a number of semi-automated, rule-based GIS tools (Geoscience Australia’s Semi-automated Morphological Mapping Tools - GA-SaMMT) to operationalise the mapping of a common set of bathymetric high and bathymetric low seabed Morphological Features. The tools have a graphical user interface and were developed using Python scripts under the widely-adopted proprietary ArcGIS Pro platform. The utility of these tools was tested across nine case study areas that represent a diverse range of complex bathymetric and physiographic settings. Overall, the mapping results are found to be more consistent than manual mapping and allow for capture of greater detail across a range of spatial scales. The mapping results demonstrate a number of advantages of GA-SaMMT, including: 1) requirement of only a bathymetry grid as sole data input; 2) flexibility to apply domain knowledge to user-defined tool parameters, or to instead use the default parameter settings; 3) repeatability and consistency in the mapping outputs when using a consistent set of tool parameters (user defined or default); 4) high-degree of objectivity; and 5) efficiency in mapping a large number (thousands) of seabed morphology features in a single dataset. In addition, GA-SaMMT can comprehensively quantify the characteristics of individual seabed bathymetric high and low features, respectively generating 34 and 46 metrics for each type of feature. Our results indicate that attribute metrics are invaluable in the interpretation and modelling of mapped Morphology Features and provide insights into their formative processes and habitat potential for marine communities.

BackgroundThe Royal Flying Doctor Service of Australia (RFDS) established a unique SARS-CoV-2 vaccination program for vaccinating Australians that live in rural and remote areas. This paper describes the preparation and response phases of the RFDS response.MethodsThis study includes vaccinations conducted by the RFDS from 01 January 2021 until 31 December 2021 when vaccines were mandatory for work and social activities. Prior to each clinic, we conducted community consultation to determine site requirements, patient characteristics, expected vaccination numbers, and community transmission rates.FindingsNinety-five organizations requested support. The majority (n = 60; 63.2%) came from Aboriginal Community Controlled Health Organizations. Following consultation, 360 communities were approved for support. Actual vaccinations exceeded expectations (n = 70,827 vs. 49,407), with a concordance correlation coefficient of 0.88 (95% CI, 0.83, 0.93). Areas that reported healthcare workforce shortages during the preparation phase had the highest population proportion difference between expected and actual vaccinations. Areas that reported high vaccine hesitancy during the preparation phase had fewer than expected vaccines. There was a noticeable increase in vaccination rates in line with community outbreaks and positive polymerase chain reaction cases [r (41) = 0.35, p = 0.021]. Engagement with community leaders prior to clinic deployment was essential to provide a tailored response based on community expectations.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2) may cause inflammation and increased cytokine secretion. Dietary factors may play an important role in enhancing the immune responses against infectious diseases such as SARS-COV-2. This narrative review aims to determine the effectiveness of macronutrients and probiotics to improve immunity in SARS-COV-2 patients. Dietary proteins may boost pulmonary function in SARS-COV-2 patients through inhibitory effects on the Angiotensin-converting enzyme (ACE) and reduce Angiotensin (ANG-II). Moreover, omega-3 fatty acids may improve oxygenation, acidosis, and renal function. Dietary fiber may also produce anti-inflammatory effects by reducing the level of high-sensitivity C-Reactive Protein (hs-CRP), Interleukin (IL-6), and Tumor necrosis factor (TNF-α). In addition, some evidence indicates that probiotics significantly improve oxygen saturation which may enhance survival rate. In conclusion, the consumption of a healthy diet including adequate macronutrients and probiotic intake may decrease inflammation and oxidative stress. Following this dietary practice is likely to strengthen the immune system and have beneficial effects against SARS-COV-2.

The successful outcomes of chimeric antigen receptor (CAR) T-cell therapy in treating hematologic cancers have increased the previously unprecedented excitement to use this innovative approach in treating various forms of human cancers. Although researchers have put a lot of work into maximizing the effectiveness of these cells in the context of solid tumors, few studies have discussed challenges and potential strategies to overcome them. Restricted trafficking and infiltration into the tumor site, hypoxic and immunosuppressive tumor microenvironment (TME), antigen escape and heterogeneity, CAR T-cell exhaustion, and severe life-threatening toxicities are a few of the major obstacles facing CAR T-cells. CAR designs will need to go beyond the traditional architectures in order to get over these limitations and broaden their applicability to a larger range of malignancies. To enhance the safety, effectiveness, and applicability of this treatment modality, researchers are addressing the present challenges with a wide variety of engineering strategies as well as integrating several therapeutic tactics. In this study, we reviewed the antigens that CAR T-cells have been clinically trained to recognize, as well as counterstrategies to overcome the limitations of CAR T-cell therapy, such as recent advances in CAR T-cell engineering and the use of several therapies in combination to optimize their clinical efficacy in solid tumors.

IntroductionNon-alcoholic fatty liver disease (NAFLD) results from an excessive accumulation of fat particles that causes liver inflammation, which ultimately causes liver damage. There is still considerable uncertainty about the effects of any nutritional supplements compared to no additional intervention. This review aimed to evaluate the efficacy of Allium sativum (A. sativum), known as garlic, in preventing and treating NAFLD.MethodsA systematic search based on a search strategy consisting of two components of “NAFLD” and “Allium sativum” in databases including PubMed, Web of Science (WoS), and SCOPUS was conducted on papers evaluating the effects of A. sativum on NAFLD treatment and prevention. We obtained studies from inception until 20 September 2022, followed by study selection and data extraction based on our eligibility criteria. Consequently, qualitative and quantitative synthesis was conducted.ResultsOur qualitative analysis reveals that A. sativum consumption is linked to the prevention of NAFLD, especially in males, although qualitative data in this study regarding the therapeutic properties of NAFLD was controversial. Our meta-analysis showed that NAFLD patients treated with A. sativum have significantly declined aminotransferase levels. That is to say, our meta-analysis revealed a lower alanine transaminase (ALT) (SMD = −0.580, 95%CI = −0.822 to −0.338), and aspartate transaminase (AST(SMD = −0.526, 95%CI = −0.767 to −0.284) in NAFLD patients treated with A. sativum compared to the placebo group. Also, pooling data from case-control studies showed that A. sativum consumption decreases the odds of being diagnosed with NAFLD by 46% (OR = 0.538, 95%CI = 0.451–0.625).ConclusionA. sativum consumption is not merely associated with NAFLD prevention but also results in a considerable decline in blood aminotransferase levels in patients diagnosed with NAFLD. To put it simply, A. sativum is linked to a decline in AST and ALT, which are considered reliable biomarkers of NAFLD response to treatment. Nevertheless, A. sativum is insufficient to improve NAFLD independent of other dietary amendments and lifestyle modifications.

Respiratory infectious diseases encountered early in life may result in life-threatening disease in neonates, which is primarily explained by the relatively naive neonatal immune system. Whereas vaccines are not readily available for all infectious diseases, vaccinations have greatly reduced childhood mortality. However, repeated vaccinations are required to reach protective immunity in infants and not all vaccinations are effective at young age. Moreover, protective adaptive immunity elicited by vaccination wanes more rapidly at young age compared to adulthood. The infant adaptive immune system has previously been considered immature but this paradigm has changed during the past years. Recent evidence shows that the early life adaptive immune system is equipped with a strong innate-like effector function to eliminate acute pathogenic threats. These strong innate-like effector capacities are in turn kept in check by a tolerogenic counterpart of the adaptive system that may have evolved to maintain balance and to reduce collateral damage. In this review, we provide insight into these aspects of the early life’s adaptive immune system by addressing recent literature. Moreover, we speculate that this shift from innate-like and tolerogenic adaptive immune features towards formation of immune memory may underlie different efficacy of infant vaccination in these different phases of immune development. Therefore, presence of innate-like and tolerogenic features of the adaptive immune system may be used as a biomarker to improve vaccination strategies against respiratory and other infections in early life.

IntroductionOpium dependence is a significant health concern in low and middle-income countries, leading to a considerable number of deaths annually. Opium has several detrimental effects on its consumers. Data regarding the impact of opium on stroke are controversial. The objective of this study is to evaluate the association between opium dependence and stroke.MethodsI conducted a systematic search based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to evaluate the association between opium dependence and stroke. Following the extraction of qualitative findings from included studies, a meta-analysis was performed to assess the pooled estimate of odds ratios (ORs).ResultsEight and four studies were included in qualitative and quantitative synthesis, respectively. Opium dependence increases the hazard of stroke mortality. Also, opium increases the odds of ischemic stroke by 127% (pooled OR = 2.27, 95% CI: 1.47–3.07).ConclusionOpium not only merely increases the odds of being diagnosed with ischemic stroke but also leads to a notable increase in the mortality rate following stroke.

IntroductionNovel atherogenic lipid indices, including non-high-density lipoprotein cholesterol (non-HDL-C) which is calculated by subtracting the HDL-C value from the total cholesterol level, atherogenic index (ratio between triglycerides (TG) and HDL-C concentrations (TG/HDL-C)), and Diff-C (calculated by subtracting low-density lipoprotein (LDL-C) from non-HDL-C), have been known as valuable predictors of dyslipidemia and subsequent cardiovascular diseases. Previous studies have reported the potential association of novel atherogenic lipid indices with metabolic syndrome (MetS). This meta-analysis aimed to assess the pooled association of novel atherogenic lipid indices with MetS or its components.MethodsA systematic search was conducted through PubMed, Scopus, and Web of Science (WoS) databases from January 2000 until March 2021 to evaluate the association of novel atherogenic lipid indices, including non-HDL-C, atherogenic index, and the difference between non-HDL-C and LDL-C (Diff-C) with MetS. Observational studies were included without any language restriction. As exclusive studies evaluating the association of non-HDL-C with metabolic syndrome (MetS) were eligible to be included in quantitative analyses, a random-effect meta-analysis was performed to pool the odds ratios (ORs). A stratified meta-analysis was performed based on the definition of MetS [Adult Treatment Panel (ATP) and International Diabetes Federation (IDF)] and the studied population.ResultsOverall, 318 studies were retrieved from an initial systematic search. After screening, 18 and five studies were included in the qualitative and quantitative syntheses, respectively. Qualitative synthesis revealed an association between non-HDL-C, Diff-C, and atherogenic index with MetS and its components. Stratified meta-analysis showed that an increased non-HDL-C level was associated with an increased odds of MetS based on ATP criteria (OR: 3.77, 95% CI: 2.14-5.39) and IDF criteria (OR: 2.71, 95% CI: 1.98-3.44) in adults (OR: 3.53, 95% CI: 2.29-4.78) and in children (OR: 2.27, 95% CI: 1.65-2.90).ConclusionNovel atherogenic lipid indices, including atherogenic index, Diff-c, and non-HDL-C, are strongly associated with increased odds of MetS and its components. The indices could be considered as potential predictors of MetS and its components in clinical practice.

IntroductionAlthough vaccination is the most effective way to limit and overcome the COVID-19 pandemic, a considerable fraction of them are not intended to get vaccinated. This study aims to investigate the existing research evidence and evaluate the effectiveness and consequences of all incentives provided for increasing the uptake of COVID-19 vaccination.MethodsA systematic search in PubMed, Web of Science (WoS), and SCOPUS from 2020 until October 10, 2021, was conducted on experimental studies evaluating the effects of incentives including cash, lottery voucher, and persuasive messages on COVID-19 vaccination intention and uptake. The study selection process, data extraction, and quality assessment were conducted independently by two investigators using Consolidated Standards of Reporting Trials (CONSORT 2010) checklist.ResultsTwenty-four records were included in the qualitative analysis. Most of the included studies assessed the effect of financial incentives. In 14 studies (58%) the assessed outcome was vaccination uptake and in nine (37.5%) others it was vaccination intention. One study considered self-reported vaccination status as the outcome. This study shows that high financial incentives and the Vax-a-million lottery are attributed to a higher vaccination rate, while the low amount of financial incentives, other lotteries, and persuasive messages have small or non-significant effects.ConclusionPaying a considerable amount of cash and Vax-a-million lottery are attributed to a higher vaccination. Nevertheless, there is a controversy over the effect of other incentives including other lotteries, low amount of cash, and messages on vaccination. It is noteworthy that, inconsistency and imprecision of included studies should be considered.

Recent studies have shown that several children diagnosed with COVID-19 have developed Kawasaki Disease (KD)-like symptoms. This systematic review aims to assess the demographic, laboratory, and clinical characteristics of children with KD-like syndrome during the COVID-19 pandemic and evaluate efficacy of treatments and patients' outcome. A comprehensive search was carried out systematically through PubMed, Scopus, and Web of Science (WoS), medRxiv, and bioRxiv by two reviewers independently for all studies or preprints data on the demographic, laboratory, and clinical characteristics of children with K.D-like signs during the COVID-19 outbreak. Overall, 378 studies were identified by the systematic search, of which 25 studies were included in the study. The included studies involved 599 patients in total. Thirteen studies (52%) were case reports or case series, and the rest (48%) were cohort studies. In 19 studies, patients were diagnosed with Multisystem inflammatory syndrome in children (MIS-C). In 16 studies COVID-19 was diagnosed in all patients based on their polymerase chain reaction result, serological findings, and computed tomography results. Higher C-reactive protein and erythrocyte sedimentation rate level were the most prevalent laboratory findings. In most studies, patients had leucopenia with marked lymphopenia, hypoalbuminemia, and increased ferritin, as well as hyponatremia. Abnormal echocardiography and respiratory outcomes were the most common clinical outcomes. In 11 studies, all patients required intensive care unit admission. Findings of the present systematic review show that the incidence of KD-like syndrome in the COVID-19 pandemic increased significantly. Moreover, this study offers new insights in the KD-like syndrome pathogenesis and clinical spectrum during COVID-19 pandemic.

Zika virus (ZIKV) dramatically emerged in French Polynesia and subsequently in the Americas where it has been associated with severe neurological complications in adults and newborns, respectively. Although plasmacytoid dendritic cells (pDCs) are a key sensor of viral infection and are critical for initiating an antiviral response, little is known about the impact of ZIKV infection on pDCs. Here, we investigated the susceptibility of human pDCs to infection with multiple strains of ZIKV and further investigated the impact of infection on pDCs functions. We observed that pDCs were refractory to cell-free ZIKV virions but were effectively infected when co-cultured with ZIKV-infected cells. However, exposure of pDCs to ZIKV-infected cells resulted in limited maturation/activation with significant down regulation of CD303 expression, a severe impairment of inflammatory cytokine production, and an inability to mount an IFN-α response. We show that ZIKV developed a strategy to inhibit the IFN-α response in primary human pDCs likely mediated through NS1-dependent CD303 signaling, thus suggesting a new mechanism of immune evasion.

Chicken and pork are the most frequently consumed meat products in the Philippines. Swine and poultry are reared in either commercial farms (CMf) or backyard farms (BYf); the latter production system is relatively common and essential to food security in low- and middle-income countries (LMICs) such as the Philippines. Similar to resource-limited LMICs, antimicrobial use (AMU) surveillance has not yet been established; thus, AMU in food animals is a knowledge gap in understanding the emergence of antimicrobial resistance (AMR) in zoonotic foodborne bacteria in the country. This qualitative AMU pilot study aims to describe the antimicrobial active ingredients (AAIs) used and associated AMU practices (e.g., source of AAIs and informed AMU decisions) by poultry and swine CMf and BYf in the Philippines. Ninety-three farms across four regions in the Philippines voluntarily provided AMU information as part of a larger biosecurity and good practices study. The percentage of farms using AAI over the total number of farms was the metric used to describe AMU. In total, there were 30 AAIs used (CMf: n =27 and BYf: n = 13); per farm, the number of AAIs used ranged from 1 to 7. The spectrum of AAIs was more diverse in swine (n = 24) compared to poultry (n = 18). Enrofloxacin was the most frequently reported AAI in poultry (33%) and swine (36%) farms. Respiratory diseases were the most frequently reported reason for AMU in both species. Between production systems, significant differences were observed in the percentage of farms using amoxicillin (27% CMf vs. 3% BYf), colistin (17% CMf vs. 3% BYf), and oxytetracycline (12% CMf vs. 39% BYf). In terms of AMU practices, of important concern was the over-the-counter access of AAIs at retail outlets and the limited veterinary oversight in BYf. Our data indicated that antimicrobials critically important for human medicine are frequently used in poultry and swine farms in the Philippines. This study can inform the development of guidelines for curbing AMR through prudent AMU and serves as a reference point for AMU surveillance capacity development in the Philippines.

Vitamin D deficiency and insufficiency (VDD) are widely recognized as risk factors for respiratory tract infections. Vitamin D influences expression of many genes with well-established relevance to airway infections and relevant to immune system function. Recently, VDD has been shown to be a risk factor for acquisition and severity of COVID-19. Thus, treating VDD presents a safe and inexpensive opportunity for modulating the severity of the disease. VDD is common in those over 60 years of age, many with co-morbid conditions and in people with skin pigmentation sufficient to reduce synthesis of vitamin D. Exposure to fine particulate air pollution is also associated with worse outcomes from COVID19. Vitamin D stimulates transcription of cathelicidin which is cleaved to generate LL37. LL37 is an innate antimicrobial with demonstrated activity against a wide range of microbes including envelope viruses. LL37 also modulates cytokine signaling at the site of infections. Fine particles in air pollution can interfere with LL37 destruction of viruses and may reduce effective immune signaling modulation by LL37. While vitamin D influences transcription of many immune related genes, the weakened antimicrobial response of those with VDD against SARS-CoV-2 may be in part due to reduced LL37.Conclusion: Vitamin D plays an important role reducing the impact of viral lung disease processes. VDD is an acknowledged public health threat that warrants population-wide action to reduce COVID-19 morbidity and mortality. While vitamin D influences transcription of many immune related genes, the weakened antimicrobial response of those with VDD against SARS-CoV-2 may be in part due to reduced LL37. Action is needed to address COVID-19 associated risks of air pollution from industry, transportation, domestic sources and from primary and second hand tobacco smoke.

At a fundamental level most genes, signaling pathways, biological functions and organ systems are highly conserved between man and all vertebrate species. Leveraging this conservation, researchers are increasingly using the experimental advantages of the amphibian Xenopus to model human disease. The online Xenopus resource, Xenbase, enables human disease modeling by curating the Xenopus literature published in PubMed and integrating these Xenopus data with orthologous human genes, anatomy, and more recently with links to the Online Mendelian Inheritance in Man resource (OMIM) and the Human Disease Ontology (DO). Here we review how Xenbase supports disease modeling and report on a meta-analysis of the published Xenopus research providing an overview of the different types of diseases being modeled in Xenopus and the variety of experimental approaches being used. Text mining of over 50,000 Xenopus research articles imported into Xenbase from PubMed identified approximately 1,000 putative disease- modeling articles. These articles were manually assessed and annotated with disease ontologies, which were then used to classify papers based on disease type. We found that Xenopus is being used to study a diverse array of disease with three main experimental approaches: cell-free egg extracts to study fundamental aspects of cellular and molecular biology, oocytes to study ion transport and channel physiology and embryo experiments focused on congenital diseases. We integrated these data into Xenbase Disease Pages to allow easy navigation to disease information on external databases. Results of this analysis will equip Xenopus researchers with a suite of experimental approaches available to model or dissect a pathological process. Ideally clinicians and basic researchers will use this information to foster collaborations necessary to interrogate the development and treatment of human diseases.

Many FA who flew prior to the ban on smoking in commercial aircraft exhibit an unusual pattern of long-term pulmonary dysfunction. This randomized controlled study tested the hypothesis that digitally delivered meditative movement (MM) training improves chronic obstructive pulmonary disease (COPD)-related symptoms in flight attendants (FA) who were exposed to second-hand cigarette smoke (SHCS) while flying. Phase I of this two-phase clinical trial was a single-arm non-randomized pilot study that developed and tested methods for MM intervention; we now report on Phase II, a randomized controlled trial comparing MM to a control group of similar FA receiving health education (HE) videos. Primary outcomes were the 6-min walk test and blood levels of high sensitivity C-reactive protein (hs-CRP). Pulmonary, cardiovascular, autonomic and affective measures were also taken. There were significant improvements in the 6-min walk test, the Multidimensional Assessment of Interoceptive Awareness (MAIA) score, and the COPD Assessment Test. Non-significant trends were observed for increased dehydroepiandrosterone sulfate (DHEAS) levels, decreased anxiety scores and reduced blood hs-CRP levels, and increased peak expiratory flow (PEF). In a Survey Monkey questionnaire, 81% of participants who completed pre and post-testing expressed mild to strong positive opinions of the study contents, delivery, or impact, while 16% expressed mild negative opinions. Over the course of the year including the study, participant adoption of the MM practices showed a significant and moderately large correlation with overall health improvement; Pearson's R = 0.62, p < 0.005. These results support the hypothesized benefits of video-based MM training for this population. No adverse effects were reported.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT02612389

A study protocol is presented for the investigation of Meditative Movement (MM) as a treatment for pulmonary dysfunction in Flight Attendants (FA) who were exposed to second-hand cigarette smoke (SHCS) while flying before the smoking ban. The study will have three parts, some of which will run concurrently. The first is a data gathering and screening phase, which will gather data on pulmonary and other aspects of the health of FA, and will also serve to screen participants for the other phases. Second is an exercise selection phase, in which a variety of MM exercises will be taught, over a 16-week period, to a cohort of 20 FA. A subset of these exercises will be selected on the basis of participant feedback on effectiveness and compliance. Third is a 52-week randomized controlled trial (RCT) to evaluate the effectiveness of a digitally delivered form of the previously selected exercises on a group of 20 FA, as compared with an attention control group. Outcome measures to be used in all three parts of the study include the six-minute walk test as a primary measure, as well as a range of biomarkers, tests and questionnaires documenting hormonal, cardio-respiratory, autonomic and affective state. This study is registered at ClinicalTrials.gov. Identifier: NCT02612389.

AbstractSmokers and individuals exposed to second hand cigarette smoke (SHCS) have a higher risk of developing chronic sinus and bronchial infections. This suggests that cigarette smoke (CS) has adverse effects on immune defenses against pathogens. Epithelial cells are important in airway innate immunity and are the first line of defense against infection. Airway epithelial cells form a physical barrier, but also respond to the presence of microbes by secreting antimicrobials, cytokines and chemokines. These molecules can lyse infectious microorganisms and/or provide signals critical to the initiation of adaptive immune responses. We examined the effects of cigarette smoke on antimicrobial secretions of primary human nasal epithelial cells (PHNEC). Compared to non-CS exposed individuals, PHNEC from in-vivo cigarette smoke exposed individuals secreted less CCL20, BD-1, and SLPI apically, less BD-1 and SLPI basolaterally, and more CCL20 basolaterally. Cigarette smoke extract (CSE) exposure in vitro decreased the apical secretion of CCL20 and beta defensin-1 by PHNEC from non-CS exposed individuals. Exposing PHNEC from non-CS exposed to cigarette smoke extract also significantly decreased the levels of many mRNA transcripts that are involved in immune signaling. Our results show that in-vivo or in vitro exposure to cigarette smoke alters the secretion of key antimicrobial peptides from PHNEC, but that in-vivo CS exposure is a much more important modifier of antimicrobial peptide secretion. Based on the gene expression data, it appears that cigarette smoke extract disrupts multiple immune signaling pathways in PHNEC. Our results provide mechanistic insight into how cigarette smoke exposure alters the innate immune response and increases an individual’s susceptibility to pathogen infection.

Regulatory T-cells (Tregs) act at the interface of host and pathogen interactions in human infectious diseases. Tregs are induced by a wide range of pathogens, but distinct effects of Tregs have been demonstrated for different pathogens and in different stages of infection. Moreover, Tregs that are induced by a specific pathogen may non-specifically suppress immunity against other microbes and parasites. Thus Treg effects need to be assessed not only in homologous but also in heterologous infections and vaccinations. Though Tregs protect the human host against excessive inflammation, they probably also increase the risk of pathogen persistence and chronic disease, and the possibility of disease reactivation later in life. Mycobacterium leprae and Mycobacterium tuberculosis, causing leprosy and tuberculosis (TB), respectively, are among the most ancient microbes known to mankind, and are master manipulators of the immune system towards tolerance and pathogen persistence. The majority of mycobacterial infections occurs in settings co-endemic for viral, parasitic and (other) bacterial coinfections. In this paper we discuss recent insights in the activation and activity of Tregs in human infectious diseases, with emphasis on early, late and non-specific effects in disease, coinfections and vaccination. We highlight mycobacterial infections as important models of modulation of host responses and vaccine induced immunity by Tregs.

Basic to all motile life is a differential approach/avoid response to perceived features of environment. The stages of response are initial reflexive noticing and orienting to the stimulus, preparation, and execution of response. Preparation involves a coordination of many aspects of the organism: muscle tone, posture, breathing, autonomic functions, motivational/emotional state, attentional orientation and expectations. The organism organizes itself in relation to the challenge. We propose to call this the preparatory set (PS). We suggest that the concept of the PS can offer a more nuanced and flexible perspective on the stress response than do current theories. We also hypothesize that the mechanisms of bodymind therapeutic and educational systems (BTES) can be understood through the PS framework. We suggest that the BTES, including meditative movement, meditation, somatic education, and the body-oriented psychotherapies, are approaches that use interventions on the PS to remedy stress and trauma. We discuss how the PS can be adaptive or maladaptive, how BTES interventions may restore adaptive PS, and how these concepts offer a broader and more flexible view of the phenomena of stress and trauma. We offer supportive evidence for our hypotheses, and suggest directions for future research. We believe that the PS framework will point to ways of improving the management of stress and trauma, and that it will suggest directions of research into the mechanisms of action of BTES.

Here we present a theory of human trauma and chronic stress, based on the practice of Somatic Experiencing® (SE), a form of trauma therapy that emphasizes guiding the client's attention to interoceptive, kinesthetic and proprioceptive experience. SE™ claims that this style of inner attention, in addition to the use of kinesthetic and interoceptive imagery, can lead to the resolution of symptoms resulting from chronic and traumatic stress. This is accomplished through the completion of thwarted, biologically based, self-protective and defensive responses, and the discharge and regulation of excess autonomic arousal. We present this theory through a composite case study of an SE treatment; based on this example, we offer a possible neurophysiological rationale for the mechanisms involved, including a theory of trauma and chronic stress as a functional dysregulation of the complex dynamical system formed by the subcortical autonomic, limbic, motor and arousal systems, which we term the core response network (CRN). We demonstrate how the methods of SE help restore functionality to the CRN, and we emphasize the importance of taking into account the instinctive, bodily based protective reactions when dealing with stress and trauma, as well as the effectiveness of using attention to interoceptive,proprioceptive and kinesthetic sensation as a therapeutic tool. Finally, we point out that SE and similar somatic approaches offer a supplement to cognitive and exposure therapies, and that mechanisms similar to those discussed in the paper may also be involved in the benefits of meditation and other somatic practices.

Over the past decades, cognitive neuroscience has witnessed a shift from predominantly disembodied and computational views of the mind, to more embodied and situated views of the mind. These postulate that mental functions cannot be fully understood without reference to the physical body and the environment in which they are experienced. Within the field of contemplative science, the directing of attention to bodily sensations has so far mainly been studied in the context of seated meditation and mindfulness practices. However, the cultivation of interoceptive, proprioceptive and kinesthetic awareness is also said to lie at the core of many movement-based contemplative practices such as Yoga, Qigong and Tai Chi. In addition, it likely plays a key role in the efficacy of modern somatic therapeutic techniques such as the Feldenkrais Method and the Alexander Technique. In the current paper we examine how these practices are grounded in the concepts of embodiment, movement and contemplation, as we look at them primarily through the lens of an enactive approach to cognition. Throughout, we point to a series of challenges that arise when Western scientists study practices that are based on a non-dualistic view of mind and body.

This review focuses on Meditative Movement (MM) and its effects on anxiety, depression and other affective states. MM is a term identifying forms of exercise that use movement in conjunction with meditative attention to body sensations, including proprioception, interoception and kinesthesis. MM includes the traditional Chinese methods of Qigong (Chi Kung) and Taijiquan (Tai Chi), some forms of Yoga and other Asian practices, as well as Western Somatic practices; however this review focuses primarily on Qigong and Taijiquan. We clarify the differences between MM and conventional exercise, present descriptions of several of the key methodologies of MM, and suggest how research into these practices may be approached in a systematic way. We also present evidence for possible mechanisms of the effects of MM on affective states, including the roles of posture, rhythm, coherent breathing, and the involvement of specific cortical and subcortical structures. We survey research outcomes summarized in reviews published since 2007. Results suggest that MM may be at least as effective as conventional exercise or other interventions in ameliorating anxiety and depression; however, study quality is generally poor and there are many confounding factors. This makes it difficult to draw definitive conclusions at this time. We suggest, however, that more research is warranted, and we offer specific suggestions for ensuring high-quality and productive future studies.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. While the primary risk factor for COPD is cigarette smoke exposure, vitamin D deficiency has been epidemiologically implicated as a factor in the progressive development of COPD-associated emphysema. Because of difficulties inherent to studies involving multiple risk factors in the progression of COPD in humans, we developed a murine model in which to study the separate and combined effects of vitamin D deficiency and cigarette smoke exposure. During a 16 week period, mice were exposed to one of four conditions, control diet breathing room air (CD-NS), control diet with cigarette smoke exposure (CD-CSE), vitamin D deficient diet breathing room air (VDD-NS) or vitamin D deficient diet with cigarette smoke exposure (VDD-CSE). At the end of the exposure period, the lungs were examined by a pathologist and separately by morphometric analysis. In parallel experiments, mice were anesthetized for pulmonary function testing followed by sacrifice and analysis. Emphysema (determined by an increase in alveolar mean linear intercept length) was more severe in the VDD-CSE mice compared to control animals and animals exposed to VDD or CSE alone. The VDD-CSE and the CD-CSE mice had increased total lung capacity and increased static lung compliance. There was also a significant increase in the matrix metalloproteinase-9: tissue inhibitor of metalloproteinases-1 ratio in VDD-CSE mice compared with all controls. Alpha-1 antitrypsin expression was reduced in VDD-CSE mice as well. In summary, vitamin D deficiency, when combined with cigarette smoke exposure, seemed to accelerate the appearance of emphysemas, perhaps by virtue of an increased protease-antiprotease ratio in the combined VDD-CSE animals. These results support the value of our mouse model in the study of COPD.