Potential Association Research Articles

SLC4A4 moulds the inflammatory tumor microenvironment and predicts therapeutic expectations in colorectal cancer.

In this report, we performed a comprehensive analysis of data in colorectal cancer (CRC), to elucidate the association among Solute Carrier Family 4 Member 4 (SLC4A4) and the abundance of immunological features and immune cell infiltration in CRC, and to explore the impact of SLC4A4 on the CRC tumor microenvironment. Colorectal cancer (CRC) cases with advanced or distal metastases experience a survival rate of less than 20%, with the lack of spectral therapeutic targets and prognostic markers posing a significant challenge for CRC treatment. SLC4A4 may be a CRC-targeted therapy for which there is currently inadequate evidence Objective: To deeply and systematically reveal the characteristics of the tumor microenvironment created by SLC4A4. We downloaded RNA sequencing files (TCGA-COADREAD), clinical data for Colon Cancer (COAD) and Rectal Cancer (READ) from the Cancer Genome Atlas. We evaluated the spearman correlation of SLC4A4 with immune features, Tracking Tumor Immunophenotype (TIP) score, and immune checkpoint gene expression. SLC4A4/immunity-related differentially expressed genes (DEGs) were identified in SLC4A4 expression groups and immune groups, and an assessment system for predicting CRC prognosis was constructed based on univariate COX and multivariate COX analyses. Based on the prognostic factors in CRC, we also constructed a nomogram to assess the survival risk status of CRC. Besides, we evaluated the potential association of SLC4A4 to immunotherapy. We found that SLC4A4 expression trended positively with immune checkpoint expression (PD-L1, CTLA4) and promoted infiltration of 27 immune cells. SLC4A4 promoted the infiltration of CD8 T cells, Dendritic cells, Macrophage, NK cells, and Th1 cells in CRC, shaping the inflammatory tumor microenvironment. Up-regulation of SLC4A4 expression might promote drug response to Anti-FGFR3_therapy, Anti-PPARG_therapy, Nivolumab, Ipilimumab in CRC patients, and down-regulation of SLC4A4 expression might promote drug response to Anti-EGFR_therapy, Aflibercept drug response. Based on the SLC4A4/immunization-related DEGs, we constructed RiskScore to assess the prognosis of CRC, which showed excellent predictive effect and robustness. RiskScore showed a trend of negative correlation with SLC4A4, which was consistent with the trend of the effect of SLC4A4 on CRC survival. Besides, RiskScore could also be useful for predicting patient prognosis. Finally, we constructed a nomogram for predicting CRC survival based on metrics with independent prognostic value (Age, M stage, Stage, RiskScore), which showed potential clinical value. Overall, upregulation of SLC4A4 expression promoted an inflammatory tumor microenvironment in CRC, and RiskScore predicted therapeutic expectancy. SLC4A4 could be a potentially clinically valuable target for CRC therapy.

Metabolic dynamics in astrocytes and microglia during post-natal development and their implications for autism spectrum disorders.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by elusive underlying mechanisms. Recent attention has focused on the involvement of astrocytes and microglia in ASD pathology. These glial cells play pivotal roles in maintaining neuronal homeostasis, including the regulation of metabolism. Emerging evidence suggests a potential association between ASD and inborn errors of metabolism. Therefore, gaining a comprehensive understanding of the functions of microglia and astrocytes in ASD is crucial for the development of effective therapeutic interventions. This review aims to provide a summary of the metabolism of astrocytes and microglia during post-natal development and the evidence of disrupted metabolic pathways in ASD, with particular emphasis on those potentially important for the regulation of neuronal post-natal maturation by astrocytes and microglia.

Does language teachers’ intercultural competence influence oral participation in EFL classrooms?: unveiling learner perspectives through a mixed methods inquiry

ABSTRACT The present two-phased sequential explanatory mixed methods study investigates the potential association between foreign language teachers’ (FLTs) intercultural competence and Japanese students’ oral participation through the perspectives of students. In Study 1, a survey questionnaire was administered to second-year advanced-level students at two Japanese universities (N = 115). The participants were asked about their learning styles and FLTs’ teaching practices that promoted and hindered their oral participation based on their prior language learning experiences. The results confirmed the associations between FLTs’ host language proficiency, host cultural understanding, and students’ oral participation. In Study 2, qualitative data were obtained from 21 students to explain and build upon the quantitative results. The findings showed that demonstrating intercultural competence by emphasizing group work, showing tolerance for silence, and using Japanese gestures, personal anecdotes, and stories from Japanese culture could create avenues to students’ own worlds and give them psychological safety to express themselves. The study concludes that FLTs’ intercultural competence needs to be further emphasized in teacher training manuals and school curricula in Japanese EFL settings.

A280 HEPATOBILIARY DISEASE IN INDIVIDUALS LIVING WITH FRAGILE X SYNDROME: A CASE SERIES

Abstract Background Fragile X syndrome is a genetic disorder known to cause intellectual disability through decreased or absent FMR protein (FMRP). Basic science studies have identified potential associations with hepatobiliary inflammation. Clinical reports of liver disease in Fragile X syndrome are however infrequent. Aims We describe 3 individuals living with Fragile X syndrome and chronic liver disease. Methods A case series and literature review were performed. Results The 1st person is a woman with concurrent Fragile X and autosomal recessive polycystic kidney disease, initially seen by Hepatology at 18 y.o. with evidence of hepatic fibrosis on abdominal ultrasound with normal liver enzymes (Table 1). She subsequently developed liver cirrhosis and portal hypertension, as well as biliary duct dilatation seen on MRI. Her overall presentation was thought to be in keeping with Caroli syndrome and congenital hepatic fibrosis, and she is currently pending genetic screening for hepatorenal ciliopathy. The 2nd person is a woman with Fragile X syndrome and ulcerative colitis, who initially presented to Hepatology at 24 y.o. with mixed liver enzyme abnormalities. Lab tests over time revealed immunology suggestive of autoimmune hepatitis (AIH) (Table 1). Subsequent investigations demonstrated primary sclerosing cholangitis (PSC) with cirrhosis. Her disease is currently managed as AIH/PSC overlap syndrome with ursodeoxycholic acid (UDCA), tacrolimus, mycophenolate, and budesonide. The 3rd person is a man with Fragile X syndrome who initially presented to Hepatology at 17 y.o. with acute hepatitis with AIH immunology (Table 1). Liver biopsy at the time demonstrated findings suggestive of early PSC as well as possible AIH. He continued to have progressive cirrhosis as well as overt PSC on subsequent abdominal imaging and is currently managed as AIH/PSC overlap syndrome with UDCA, azathioprine, and budesonide. A review of literature revealed that asides from known intellectual, behavioral, and physical effects of Fragile X syndrome, there are minimal reports of other associated medical complications including liver problems or autoimmune conditions including IBD. There are however reports of autoimmunity in those with altered FMR1 (Fragile X Mental Retardation 1) gene mutations. Conclusions These 3 cases of liver disease in Fragile X highlight young age of presentation for chronic liver disease with both biliary and immune-mediated characteristics, along with progression to cirrhosis. Additional review for liver manifestations in people living with Fragile X would help understand if this association is incidental or causal. Investigations of individuals with Fragile X syndrome and liver disease Funding Agencies None

Under-Diagnosis of Dementia with Lewy Bodies in Individuals Racialized as Black: Hypotheses Regarding Potential Contributors.

Dementia with Lewy bodies (DLB) is one of the most common degenerative dementias after Alzheimer's disease (AD) dementia. DLB is under-diagnosed across populations but may be particularly missed in older Black adults. The object of this review was to examine key features of DLB and potential associations with race in order to hypothesize why DLB may be under-diagnosed in Black adults in the U.S. In terms of dementia, symptoms associated with high rates of co-pathology (e.g., AD, vascular disease) in older Black adults may obscure the clinical picture that might suggest Lewy body pathology. Research also suggests that clinicians may be predisposed to give AD dementia diagnoses to Black adults, potentially missing contributions of Lewy body pathology. Hallucinations in Black adults may be misattributed to AD or primary psychiatric disease rather than Lewy body pathology. Research on the prevalence of REM sleep behavior in diverse populations is lacking, but REM sleep behavior disorder could be under-diagnosed in Black adults due to sleep patterns or reporting by caregivers who are not bed partners. Recognition of parkinsonism could be reduced in Black adults due to clinician biases, cultural effects on self-report, and potentially underlying differences in the frequency of parkinsonism. These considerations are superimposed on structural and systemic contributions to health (e.g., socioeconomic status, education, structural racism) and individual-level social exposures (e.g., social interactions, discrimination). Improving DLB recognition in Black adults will require research to investigate reasons for diagnostic disparities and education to increase identification of core symptoms in this population.

Clinical relevance of transcranial Doppler in a cardiac surgery setting: embolic load predicts difficult separation from cardiopulmonary bypass

BackgroundDuring cardiac surgery, transcranial Doppler (TCD) represents a non-invasive modality that allows measurement of red blood cell flow velocities in the cerebral arteries. TCD can also be used to detect and monitor embolic material in the cerebral circulation. Detection of microemboli is reported as a high intensity transient signal (HITS). The importance of cerebral microemboli during cardiac surgery has been linked to the increased incidence of postoperative renal failure, right ventricular dysfunction, and hemodynamic instability. The objective of this study is to determine whether the embolic load is associated with hemodynamic instability during cardiopulmonary bypass (CPB) separation and postoperative complications.MethodsA retrospective single-centre cohort study of 354 patients undergoing cardiac surgery between December 2015 and March 2020 was conducted. Patients were divided in tertiles, where 117 patients had a low quantity of embolic material (LEM), 119 patients have a medium quantity of microemboli (MEM) and 118 patients who have a high quantity of embolic material (HEM). The primary endpoint was a difficult CPB separation. Multivariate logistic regression was used to determine the potential association between a difficult CPB separation and the number of embolic materials.ResultsPatients who had a difficult CPB separation had more HITS compared to patients who had a successful CPB separation (p < 0.001). In the multivariate analysis, patients with MEM decreased their odds of having a difficult CPB weaning compared to patients in the HEM group (OR = 0.253, CI 0.111–0.593; p = 0.001). In the postoperative period patients in the HEM group have a higher Time of Persistent Organ Dysfunction (TPOD), a longer stay in the ICU, a longer duration under vasopressor drugs and a higher mortality rate compared to those in the MEM and LEM groups.ConclusionThe result of this study suggests that a high quantity of cerebral embolic material increases the odds of having a difficult CPB separation. Also, it seems to be associated to more complex surgery, a longer CPB time, a higher TPOD and a longer stay in the ICU. Six out of eight patients who died in this cohort were in the HEM group.

Association between systemic immune inflammation index, systemic inflammation response index and adult psoriasis: evidence from NHANES.

The systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) are both novel biomarkers and predictors of inflammation. Psoriasis is a skin disease characterized by chronic inflammation. This study aimed to investigate the potential association between SII, SIRI, and adult psoriasis. Data of adults aged 20 to 80 years from the National Health and Nutrition Examination Survey (NHANES) (2003-2006, 2009-2014) were utilized. The K-means method was used to group SII and SIRI into low, medium, and high-level clusters. Additionally, SII or SIRI levels were categorized into three groups: low (1st-3rd quintiles), medium (4th quintile), and high (5th quintile). The association between SII-SIRI pattern, SII or SIRI individually, and psoriasis was assessed using multivariate logistic regression models. The results were presented as odds ratios (ORs) and confidence intervals (CIs). Restricted cubic spline (RCS) regression, subgroup, and interaction analyses were also conducted to explore the potential non-linear and independent relationships between natural log-transformed SII (lnSII) levels or SIRI levels and psoriasis, respectively. Of the 18208 adults included in the study, 511 (2.81%) were diagnosed with psoriasis. Compared to the low-level group of the SII-SIRI pattern, participants in the medium-level group had a significantly higher risk for psoriasis (OR = 1.40, 95% CI: 1.09, 1.81, p-trend = 0.0031). In the analysis of SII or SIRI individually, both SII and SIRI were found to be positively associated with the risk of psoriasis (high vs. low group OR = 1.52, 95% CI: 1.18, 1.95, p-trend = 0.0014; OR = 1.48, 95% CI: 1.12, 1.95, p-trend = 0.007, respectively). Non-linear relationships were observed between lnSII/SIRI and psoriasis (both p-values for overall < 0.05, p-values for nonlinearity < 0.05). The association between SII levels and psoriasis was stronger in females, obese individuals, people with type 2 diabetes, and those without hypercholesterolemia. We observed positive associations between SII-SIRI pattern, SII, SIRI, and psoriasis among U.S. adults. Further well-designed studies are needed to gain a better understanding of these findings.

Systemic lupus erythematosus and Atopic dermatitis: A two sample Mendelian randomization study.

Systemic lupus erythematosus (SLE) and atopic dermatitis (AD) are common diseases in human populations. Previous studies have suggested a potential association between SLE and AD. However, the causal relationship and direction between the two conditions remain unclear. The aim of this study is to evaluate the causal relationship between SLE and AD. In this study, we employed Mendelian randomization (MR) analysis to investigate the causal relationship between SLE and AD. MR analysis has the advantage of reducing confounding factors, determining the direction of causality, and providing quantitative effect estimates. We obtained summary data from genome-wide association studies (GWAS) on SLE and AD from publicly available databases. Five MR methods, namely MR Egger, weighted median, inverse variance weighted, simple mode, and weighted mode, were used to assess the causal relationship between SLE and AD. Several techniques, including MR-Egger intercept, MR-PRESSO, and Cochran's Q test, were utilized to evaluate heterogeneity and pleiotropy. Our study demonstrated a causal relationship between the prevalence of SLE and an increased risk of AD (MR Egger OR: 1.567, 95% CI: [1.041, 1.285], P = 0.009; IVW OR: 1.085, 95% CI: [1.005, 1.143], P = 0.035). Furthermore, sensitivity analyses did not detect heterogeneity or pleiotropy. Our research finds that SLE is a contributing factor to the development of AD, providing valuable insights into the pathogenesis and prevention of both diseases. Key Points • Currently, there is no research that clearly indicates a causal relationship between SLE and AD. This study, for the first time, identified a positive causal relationship between SLE and AD. • The results of this study contribute to our understanding of the pathogenesis and treatment strategies for SLE and AD, providing some guidance for future clinical practice.

The association of depressive symptoms and female sexual functioning in the menopause transition: a cross-sectional study.

Sexual dysfunction is very common among middle-aged females. Several factors are considered to influence sexual functioning, including reproductive aging and associated physiological changes as well as life stressors, mental health, and other socioeconomic influences. The objectives of this study are to evaluate the effect of current depressive symptoms on sexual functioning during menopause and to further analyze whether socioeconomic status, age, and antidepressant usage impact this association. Perimenopausal and postmenopausal women aged 40 to 65 years seeking treatment from a specialized menopause clinic completed a self-report survey with the main outcome measure being the 19-item Female Sexual Function Index quantifying sexual dysfunction. We used the 10-item Center for Epidemiological Studies Depression Scale to estimate a major depressive episode. Statistical analyses were completed to assess the potential associations of socioeconomic factors, age, and antidepressant usage. Of the 269 participants, 61.3% met criteria for a major depressive episode and 67.0% had low sexual function. As predicted, women currently experiencing depressive symptoms had a greater risk of low sexual function during perimenopause and postmenopause. Antidepressant usage, low household income, being postmenopausal, and age also predicted low sexual function. Among perimenopausal and postmenopausal women, current depressive symptoms were associated with low sexual function. A biopsychosocial approach should be considered when exploring effective treatment strategies for sexual concerns among midlife women.

Vitamin D Reduces GABA-Positive Astrocytes in the 5xFAD Mouse Model of Alzheimer's Disease.

Vitamin D has neuroprotective and immunomodulating functions that may impact glial cell function in the brain. Previously, we reported molecular and behavioral changes caused by deficiency and supplementation of vitamin D in an Alzheimer's disease (AD) mouse model. Recent studies have highlighted reactive astrocytes as a new therapeutic target for AD treatment. However, the mechanisms underlying the therapeutic effects of vitamin D on the glial cells of AD remain unclear. To investigate the potential association between vitamin D deficiency/supplementation and the pathological progression of AD, including amyloid-β (Aβ) pathology and reactive astrogliosis. Transgenic hemizygous 5XFAD male mice were subjected to different dietary interventions and intraperitoneal vitamin D injections to examine the effects of vitamin D deficiency and supplementation on AD. Brain tissue was then analyzed using immunohistochemistry for Aβ plaques, microglia, and astrocytes, with quantifications performed via ImageJ software. Our results demonstrated that vitamin D deficiency exacerbated Aβ plaque formation and increased GABA-positive reactive astrocytes in AD model mice, while vitamin D supplementation ameliorated these effects, leading to a reduction in Aβ plaques and GABA-positive astrocytes. Our findings highlight the significant impact of vitamin D status on Aβ pathology and reactive astrogliosis, underscoring its potential role in the prevention and treatment of AD. This study provides the first in vivo evidence of the association between vitamin D and reactive astrogliosis in AD model mice, indicating the potential for targeting vitamin D levels as a novel therapeutic approach for AD.

Exploring the interplay between posttraumatic stress disorder, gut microbiota, and inflammatory biomarkers: a comprehensive meta-analysis.

Posttraumatic stress disorder (PTSD) is the most common mental health disorder to develop following exposure to trauma. Studies have reported conflicting results regarding changes in immune biomarkers and alterations in the abundance of bacterial taxa and microbial diversity in patients with PTSD. The purpose of this meta-analysis is to summarize existing studies examining gut microbiota characteristics and changes in immune biomarkers in patients with PTSD. Relevant studies were systematically searched in PubMed, Scopus, and Embase, published in English between January 1, 1960, and December 1, 2023. The outcomes included changes in abundance and diversity in gut microbiota (gut microbiota part) and changes in immune biomarkers (immune part). The meta-analysis included a total of 15 studies, with 9 focusing on changes in inflammatory biomarkers and 6 focusing on changes in gut microbiota composition in patients with PTSD. No differences were observed between groups for all inflammatory biomarkers (P≥0.05). Two of the six studies found that people with PTSD had less alpha diversity. However, the overall Standardized Mean Difference (SMD) for the Shannon Diversity Index was not significant (SMD 0.27, 95% CI -0.62-0.609, p = 0.110). Regarding changes in abundance, in two of the studies, a significant decrease in Lachnospiraceae bacteria was observed. This meta-analysis provides a comprehensive overview of gut microbiota characteristics in PTSD, suggesting potential associations with immune dysregulation. Future research should address study limitations, explore causal relationships, and consider additional factors influencing immune function in individuals with PTSD. https://www.crd.york.ac.uk, identifier CRD42023476590.

Analysis of sexual dysfunction development among male and female living kidney donors.

Living kidney donations (LKDs) face a persistent demand for patients with end-stage renal disease, emphasizing the importance of LKDs' growth and success. Although living kidney donors generally exhibit excellent survival rates, little research has explored the development of long-term sexual dysfunction following LKD. This study aimed to analyze differences in 5-year sexual dysfunction outcomes between male and female living kidney donors, utilizing the TriNetX database, a federated network of electronic medical records from multiple U.S. healthcare organizations. A propensity score-matched cohort study compared 45-year sexual dysfunction outcomes in adult male and female living kidney donors from December 2013 to December 2022. Cohorts were matched on age; sex; race and ethnicity; diabetes, cardiovascular, genitourinary, and psychiatric comorbidities; lifestyle-related factors; and medications that may impact normal sexual functioning. Primary outcomes included hazard ratio (HR) for decreased libido, sexual dysfunction (composite of male erectile dysfunction, ejaculatory disorders, vaginismus/dyspareunia, infertility, orgasmic disorders, arousal/desire disorders), and sexually transmitted diseases. Secondary outcomes assessed sex counseling and interpersonal relationship issues with spouses or partners. The matched cohorts included 2315 patients each (male, female), and the mean age was 42.3 ± 12.5years. At 5 years, male donors had a significantly higher HR for sexual dysfunction (HR, 3.768; 95% confidence interval, 1.929-7.358). Erectile dysfunction occurred in 1% of male patients, while vaginismus/dyspareunia affected <1% of female patients. Other sexual disorders, decreased libido, sexually transmitted diseases, and incidences of sexual and interspousal counseling were not significantly different. Male living kidney donors faced a higher risk of developing sexual dysfunction 5 years after donation. While LKD remains a safe and viable alternative, clinicians and donors should be mindful of the potential association with sexual dysfunction postdonation. Further research may enhance support for the well-being of living kidney donors.

Mindfulness disposition as a protective factor against stress in Antarctica: A potential countermeasure for long-duration spaceflight?

BackgroundLong-duration missions in isolated, confined, and extreme environments, including Antarctica and upcoming deep-space operations, can be a source of increased stress. The identification of countermeasures and protective factors is required to support health and performance in similar contexts. Mindfulness disposition is an optimal candidate, but no research has ever explored this potential association. MethodsTwenty-four crew members from two Antarctic expeditions at the Concordia base were repeatedly assessed over the course of a 12-month mission for stress (Perceived Stress Scale) and mindfulness, using multiple assessment measures, including the Mindful Attention and Awareness Scale (MAAS), the Langer Mindfulness Scale (LMS), the Breath Counting Task, and the Triangle Task. ResultsResults indicate a strong negative association over time between mindfulness and stress, particularly when measured with the MAAS and the LMS. Higher MAAS baseline values were also good predictors of lower stress patterns during the mission. ConclusionsMindfulness disposition was negatively associated with stress over time, suggesting that it can play an important role in stress mitigation in isolated and confined environments, including long-duration space missions. Furthermore, a mindfulness assessment could be added to the crew selection procedure.

Hovering Is Not Helping: Relationships among Helicopter Parenting, Attachment, Academic Outcomes, and Mental Health in College Students

Helicopter parenting (or overparenting) refers to developmentally inappropriate or intrusive tactics to control a child’s behavior. Helicopter parents are usually trying to help their children, but their behavior has been associated with adverse academic, adjustment, and mental health outcomes in older children (i.e., adolescents, young adults), who should be developing more autonomy. The current study examined potential associations between helicopter parenting, attachment security, and academic and mental health outcomes in college students, hypothesizing that higher rates of helicopter parenting would be associated with more insecure attachment with parental figures and closest friends, poorer mental health (i.e., higher rates of depression and/or anxiety), and reduced academic motivation, performance, and self-efficacy. Our sample of 135 college students completed measures of anxiety, depression, and somatization, academic self-efficacy and motivation, perceptions of parental involvement, and dimensions of attachment in multiple relationships (i.e., mother, father, and closest friend). As expected, the bivariate and regression analyses revealed that higher levels of parental involvement (i.e., helicopter parenting) predicted significantly more insecure parental and peer attachment, greater internalizing, and lower effort regulation among college students.

Culture- and non-culture-based approaches reveal unique features of the ocular microbiome in dry eye patients

PurposeThe purpose of this study was to investigate the ocular microbiome in individuals with dry eye disease and to identify features of their ocular microbiome of possible health and diagnostic significance. MethodsConjunctival samples were collected from both eyes in duplicate from 91 individuals (61 dry eye, 30 healthy) and used for both culture-dependent and culture-independent analyses. Samples were either analysed using next generation sequencing (V3-V4 16S rDNA) or inoculated on a wide range of agar types and grown under a broad range of conditions to maximize recovery. Isolates were identified by partial sequencing of the 16S rDNA and rpoB genes and tested for antibiotic susceptibility. We applied a L2-regularized logistic regression model on the next generation sequencing data to investigate any potential association between severe dry eye disease and the ocular microbiome. ResultsCulture-dependent analysis showed the highest number of colony forming units in healthy individuals. The majority of isolates recovered from the samples were Corynebacterium, Micrococcus sp., Staphylococcus epidermidis, and Cutibacterium acnes. Culture independent analysis revealed 24 phyla, of which Actinobacteria, Firmicutes and Proteobacteria were the most abundant. Over 405 genera were detected of which Corynebacterium was the most dominant, followed by Staphylococcus and Cutibacterium. The L2-regularized logistic regression model indicated that Blautia and Corynebacterium sp. may be associated with severe DED. ConclusionsOur study indicates that the ocular microbiome has characteristic features in severe DED patients. Certain Corynebacterium species and Blautia are of particular interest for future studies.

Evaluating the safety profile of calcineurin inhibitors: cancer risk in patients with systemic lupus erythematosus from the LUNA registry-a historical cohort study.

Previous studies have shown conflicting evidence regarding the incidence of cancer in patients with systemic lupus erythematosus (SLE) compared with that in healthy individuals. Calcineurin inhibitors (CNIs) such as cyclosporine and tacrolimus have been widely used to treat SLE; however, their effects on cancer risk remain unclear. We aimed to investigate the incidence of cancer in patients with SLE and determine the potential association between CNI use and cancer risk. The standardized incidence ratio (SIR) of cancer among patients with lupus in the Lupus Registry of Nationwide Institutions (LUNA) was calculated based on the age-standardized incidence rate of cancer reported by Japan's Ministry of Health, Labour and Welfare. We also examined the association between CNI exposure and cancer risk, while considering potential confounding factors. The analysis accounted for confounding variables such as age, sex, smoking history, maximum glucocorticoid dose, treatment history with cyclophosphamide, ongoing hydroxychloroquine, Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SDI) value (excluding cancer occurrence), comorbidity of diabetes mellitus, and smoking history. The study included 704 patients with SLE (625 females; 88.8%) with a median age of 44years [interquartile range (IQR) = 34-55] years. The median past maximum glucocorticoid dose was 40mg/day [IQR = 30-60mg/day], and the SDI at registration was 1 [IQR = 0-2]. Among the patients, 246 (35.1%) had smoking histories, and 38 (5.4%) experienced cancer complications. Gynecological malignancies accounted for 63.2% of all cancers. The SIR of cancer in the LUNA cohort was 1.08 (95% confidence interval [CI] = 0.74-1.43). No statistically significant risks of cancer were found in relation to CNI treatment history; the odds ratio using multiple logistic regression was 1.12 (95% CI = 0.42-3.00), the risk ratio using standardization was 1.18 (95% CI = 0.47-2.16), and the risk ratio using inverse probability weighting was 1.8 (95% CI = 0.41-4.66). The incidence of cancer in patients with SLE in the LUNA cohort did not significantly differ from that in the general population. These findings suggest that CNI treatment in this cohort did not pose a risk factor for cancer development.

Physiological and Thermal Sensation Responses to Severe Cold Exposure (−20 °C)

Various jobs, indoors and outdoors, are subjected to severe cold temperatures during daily activities. Extremely low-temperature exposure and work intensity affect health, safety, and occupational performance. This work aimed to assess the physiological and thermal sensation responses before, during, and following a 60 min exposure to cold (−20 °C), during which occupational activities were developed. Using ingestible telemetric temperature pills, eight skin temperature sensors, blood pressure equipment, and the Thermal Sensation Questionnaire, experiments were conducted with 11 healthy male volunteers wearing highly insulating cold protective clothing. The most notorious alterations were reported in mean skin temperatures and thermal sensation responses during the first 20 min of cold exposure. Among the eight skin temperature points, the forehead and left hand showed a higher sensitivity to cold. The mean core temperature reported significant variations throughout the protocol, with decreases during the initial 10 min of cold exposure and posterior increases despite the cold environment. Blood pressure showed slight increases from the initial to the recovery period. Overall, outcomes contribute to current scientific knowledge on physiological and perception responses in extremely cold environments while describing the influence of protective clothing and occupational activities on these responses. Future research should be developed with additional skin temperature measurements in the extremities (fingers, face, and toes) and the analysis of thermal sensation potential associations with performance changes, which can also be of great significance for future thermal comfort models.

Sudden Sensorineural Hearing Loss after COVID-19 Vaccination: A Review of the Available Evidence through the Prism of Causality Assessment.

Sudden sensorineural hearing loss (SSNHL), a rare audiological condition that accounts for 1% of all cases of sensorineural hearing loss, can cause permanent hearing damage. Soon after the launch of global COVID-19 vaccination campaigns, the World Health Organization released a signal detection about SSNHL cases following administration of various COVID-19 vaccines. Post-marketing studies have been conducted in different countries using either pharmacovigilance or medico-administrative databases to investigate SSNHL as a potential adverse effect of COVID-19 vaccines. Here, we examine the advantages and limitations of each type of post-marketing study available. While pharmacoepidemiological studies highlight the potential association between drug exposure and the event, pharmacovigilance approaches enable causality assessment. The latter objective can only be achieved if an expert evaluation is provided using internationally validated diagnostic criteria. For a rare adverse event such as SSNHL, case information and quantification of hearing loss are mandatory for assessing seriousness, severity, delay onset, differential diagnoses, corrective treatment, recovery, as well as functional sequelae. Appropriate methodology should be adopted depending on whether the target objective is to assess a global or individual risk.

Exposure to di-2-ethylhexyl phthalate (DEHP) increases the risk of cancer

Cancer is a major socioeconomic burden that seriously affects the life and spirit of patients. However, little is known about the role of environmental toxicant exposure in diseases, especially ubiquitous di-(2-ethylhexyl) phthalate (DEHP) which is one of the most widely used plasticizers. Hence, the objective of this study was to assess the potential association between cancer and DEHP. The data were collected using the 2011–2018 National Health and Nutrition Examination Survey (NHANES) data (n = 6147), and multiple logistic regression was conducted to evaluate the association. The concentrations of DEHP were calculated by each metabolite and split into quartiles for analysis. After adjusting for confounding factors, DEHP was significantly associated with an increased risk of cancer prevalence, and the metabolites of DEHP showed similar results (OR > 1.0, p < 0.05). Simultaneously, the association remained when the analyses were stratified by age and sex, and the risk of cancer appeared to be higher in male patients. In addition, further analysis suggested that DEHP exposure obviously increased the risk of female reproductive system cancer, male reproductive system cancer, and other cancers (OR > 1.0, p < 0.05) but not skin and soft tissue cancer. DEHP exposure is associated with the risk of cancer, especially female reproductive system cancer, male reproductive system cancer and other cancers.

Identification of allergens from Aspergillus fumigatus-Potential association with lung damage in asthma.

Component-resolved diagnosis allows detection of IgE sensitization having the advantage of reproducibility and standardization compared to crude extracts. The main disadvantage of the traditional allergen identification methods, 1- or 2-dimensional western blotting and screening of expression cDNA libraries with patients' IgEs, is that the native structure of the protein is not necessarily maintained. We used a novel immunoprecipitation technique in combination with mass spectrometry to identify new allergens of Aspergillus fumigatus. Magnetic Dynabeads coupled with anti-human IgE antibodies were used to purify human serum IgE and subsequently allergens from A. fumigatus protein extract. Of the 184 proteins detected by subsequent mass peptide fingerprinting, a subset of 13 were recombinantly expressed and purified. In a panel of 52 A. fumigatus-sensitized people with asthma, 23 non-fungal-sensitized asthmatics and 18 healthy individuals, only the former showed an IgE reaction by immunoblotting and/or ELISA. We discovered 11 proteins not yet described as A. fumigatus allergens, with fructose-bisphosphate aldolase class II (FBA2) (33%), NAD-dependent malate dehydrogenase (31%) and Cu/Zn superoxide dismutase (27%) being the most prevalent. With respect to these three allergens, native versus denatured protein assays indicated a better recognition of the native proteins. Seven of 11 allergens fulfilled the WHO/IUIS criteria and were accepted as new A. fumigatus allergens. In conclusion, we introduce a straightforward method of allergen identification from complex allergenic sources such as A. fumigatus by immunoprecipitation combined with mass spectrometry, which has the advantage over traditional methods of identifying allergens by maintaining the structure of the proteins.