History Of Exposure Research Articles

Humoral correlates of protection against influenza A H3N2 virus infection

Abstract Background: Gaps remain in our knowledge of the humoral correlates of protection against influenza A/H3N2, including the role of antibodies against the hemagglutinin stalk, a highly conserved but immunologically sub-dominant region. Methods: Two household studies were conducted in Managua, Nicaragua. Household contacts were tested for influenza using RT-PCR. We compared pre-existing antibody levels against full-length hemagglutinin (FLHA), HA stalk, and neuraminidase (NA) measured by ELISA, along with initial HA inhibition assay (HAI) titers, between infected and uninfected participants. Results: A total of 899 individuals participated in household activation during three A/H3N2 seasons with 329 infections occurring. A four-fold increase in initial HA stalk titers was independently associated with an 18% decrease in the risk of infection (OR=0.82, 95%CI 0.68-0.98, p=0.04). In 0-14-year-olds, anti-NA antibodies (OR=0.67, 95%CI 0.53-0.85, p<0.01) were associated with protection, but anti-HA stalk antibodies were not. In adults, anti-HA stalk antibodies were independently associated with protection (OR=0.72, 95%CI 0.54-0.95,p=0.02). Conclusions: The HA stalk is an independent correlate of protection against A/H3N2 infection, though this protection is age dependent. This supports the continued exploration of the HA stalk as a target for broadly protective influenza vaccines and suggests that the protective benefits may depend on age and influenza exposure history.

IL-10 regulates BCL-3 mediated adaptation to repeated TLR4 stimulation in macrophages

Abstract Due to its potential to initiate pathological inflammation, Toll-like receptor 4 (TLR4) mediated activation of macrophages has been studied intensely, revealing a multitude of regulatory components and mechanisms. Systematically varying dose and duration of priming and re-exposure of bone marrow derived macrophages (BMDM) to the TLR4 ligand KLA, we quantified dose-dependent adaptation and sensitization at multiple stages of the signaling response, including TLR4 internalization, MAPK activation, and nuclear translocation of transcription factors. We find that the anti-inflammatory cytokine IL-10 neither interferes with MyD88-dependent MAPK, NFkB nor TRIF-dependent IRF signaling upon restimulation after priming. Instead, IL-10 is found to affect nuclear translocation of the transcriptional regulator BCL-3 while showing a surprisingly strong dependence on the KLA exposure history. Moreover, chromatin immunoprecipitation of BCL-3 reveals that BCL-3 occupies kb sites in the TNFa and IL-6 genes in hypo-responsive macrophages in an IL-10 dependent manner. This work was supported by the intramural program of the NIAID, NIH.

Assessment of SARS-CoV-2 Spike and NCAP antigen-specific memory B cell frequency and Ig class/subclass usage following natural infection and/or COVID-19 mRNA vaccination

Abstract An adaptive humoral response can encompass multiple Ig classes/subclasses, each capable of contributing to host defense through different effector functions. Which Ig class/subclass are elicited in response to an antigen encounter is the consequence of context, such as site of antigen contact, presence of immunostimulatory motifs and the cytokine secretion signature of helper T cells. Moreover, the number of antigen encounters and duration of the ensuing immune responses can further diversify the memory B cell compartment’s epitope specificity, affinity and Ig class/subclass usage. Beyond characterization of Ig usage in blood, whether differences also exist in the Bmem compartment following multiple SARS-CoV-2 infections and/or COVID-19 vaccinations is still not well understood. Leveraging multiplexed B cell ImmunoSpot assays, the scope of this work is to characterize SARS-CoV-2 S- and N-specific Bmem and their respective Ig class/subclass usage in the context of complex immune exposure histories. In agreement with recent observations detailing the antibody response elicited following COVID-19 mRNA vaccination and/or breakthrough infection, alterations in the affinity, breadth and IgG subclass usage of S-specific Bmem was also observed. Collectively, our findings demonstrate the feasibility of performing in-depth characterization of Bmem in a streamlined pipeline that requires minimal cell material and serves to motivate usage of the multiplexed FluoroSpot platform.

Multiplexed ImmunoSpot™ enables streamlined assessment of antigen-specific B cells; lessons toward maximizing cell utilization and increasing sample throughput

Abstract There are few techniques capable of detecting rare antigen-specific B cells while also providing information regarding their abundance, Ig class/subclass usage and functional affinity. The ImmunoSpot™ assay approach is suited for such antigen-specific B cell assessments since it provides information at single-cell resolution for individual ASC. Moreover, recently introduced innovations in the implementation of this assay modality have opened the door to testing larger sample sets. Towards this objective, multiplexed B cell FluoroSpot assays reduce the cell material requirement through parallel assessment of multiple Ig classes or IgG subclasses. Nevertheless, accurate determination of ASC frequencies, especially in the context of diverse antigen panels and complex exposure histories, is best achieved through evaluating multiple cell inputs to accommodate the inherent variability present within and amongst individual donors. The scope of this research effort was to further optimize the assay pipeline to facilitate high-throughput suitable assessment of antigen-specific ASC. This goal has been achieved through introducing advancements in the image analysis software component, improving both the time requirement and precision of downstream data analysis. Collectively, implementation of these assay optimizations serves to increase the feasibility of making high-throughput assessment of antigen-specific ASC using the ImmunoSpot™ approach a routine practice in immune monitoring.

Chronic alcohol consumption alters sex-dependent BNST neuron function in rhesus macaques

Repeated alcohol drinking contributes to a number of neuropsychiatric diseases, including alcohol use disorder and co-expressed anxiety and mood disorders. Women are more susceptible to the development and expression of these diseases with the same history of alcohol exposure as men, suggesting they may be more sensitive to alcohol-induced plasticity in limbic brain regions controlling alcohol drinking, stress responsivity, and reward processing, among other behaviors. Using a translational model of alcohol drinking in rhesus monkeys, we examined sex differences in the basal function and plasticity of neurons in the bed nucleus of the stria terminalis (BNST), a brain region in the extended amygdala shown to be a hub circuit node dysregulated in individuals with anxiety and alcohol use disorder. We performed slice electrophysiology recordings from BNST neurons in male and female monkeys following daily “open access” (22 h/day) to 4% ethanol and water for more than one year or control conditions. We found that BNST neurons from control females had reduced overall current density, hyperpolarization-activated depolarizing current (Ih), and inward rectification, as well as higher membrane resistance and greater synaptic glutamatergic release and excitatory drive, than those from control males, suggesting that female BNST neurons are more basally excited than those from males. Chronic alcohol drinking produced a shift in these measures in both sexes, decreasing current density, Ih, and inward rectification and increasing synaptic excitation. In addition, network activity-dependent synaptic inhibition was basally higher in BNST neurons of males than females, and alcohol exposure increased this in both sexes, a putative homeostatic mechanism to counter hyperexcitability. Altogether, these results suggest that the rhesus BNST is more basally excited in females than males and chronic alcohol drinking produces an overall increase in excitability and synaptic excitation. These results shed light on the mechanisms contributing to the female-biased susceptibility to neuropsychiatric diseases including co-expressed anxiety and alcohol use disorder.

Prevalence and Knowledge of Tick-Borne Disease Among Forest Management Workers in Santa Cruz, California.

Background: In Lyme-endemic areas, limited research has investigated the risk of tick-borne diseases among frontline workers in fire management. This study aimed to compare the exposure histories to ticks and tick-borne pathogens, knowledge, and prevention practices between individuals engaged in fire-related forest management and those participating in recreational activities within Santa Cruz County, CA, in an area of high risk of tick exposure. Methods: Blood samples from 55 forest workers and 58 members of the public were tested for bacterial DNA of and antibodies to Borrelia burgdorferi, Anaplasma phagocytophilum, and Rickettsia species. In addition, a questionnaire was administered to 54 workers and 84 members of the public to identify gaps in knowledge and prevention practices. Results: Although workers had a higher percentage of positive B. burgdorferi antibodies than the public (5.5% compared with 1.7%), the difference was not statistically significant. Conversely, rickettsial antibodies were more prevalent among the public (17.2% versus 3.6% for workers), but specificity to pathogenic bacteria could not be confirmed. No DNA for the three pathogens or antibodies against A. phagocytophilum were detected. Many workers and members of the public reported tick bites (67.4% of participants), with a notable 11% increase among workers in the odds of being bitten for each additional year spent working in forests. Although workers took greater precautions, significant knowledge and practice gaps were identified among both populations, such as an inability to distinguish tick species from common arthropods (mites, spiders, fleas), overestimating the size of ticks, and inappropriate tick-removal techniques. Conclusion: This study underscores the risk of tick-borne diseases faced by fire management workers in Lyme disease-endemic regions. The findings emphasize the necessity for future studies of Lyme disease within this population, and highlight the urgent need for enhanced training programs to minimize these risks.

The Immune Response of Cutaneous Basosquamous- and Squamous-Cell Carcinoma Associated with Sun Exposure.

In recent years, there has been an observed increase in the frequency of cutaneous carcinoma, which correlates with sun exposure. This study aims to explore the variances of tumor characteristics and immune response markers among patients diagnosed with cutaneous squamous-cell carcinoma (SCC) and basosquamous-cell carcinoma (BSC) with varying levels of sun exposure. The objective is to elucidate the potential influence of sun exposure on tumor progression and immune response in these types of carcinomas. We conducted a retrospective observational study that included 132 patients diagnosed with SCC and BSC. Participants were separated into high- and low-sun exposure groups. Tumor characteristics and immune response markers, including lymphocyte percentage (LY%), neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR), were assessed using the Mann-Whitney U test. Our findings revealed the interplay between sun exposure, inflammation, aging, and immune response. In 80% of cases, it was found that individuals had high sun exposure throughout their lifetime. Patients in the high sun exposure category had a significantly higher LY% than those with low sun exposure (24.22 ± 7.64 vs. 20.71 ± 8.10, p = 0.041). Also, the NLR was lower in patients with high sun exposure (3.08 ± 1.47 vs. 3.94 ± 2.43, p = 0.023). Regarding inflammatory markers, the erythrocyte sedimentation rate (ESR), LY%, NLR, and LMR showed significant differences between the two groups. Patients who were diagnosed with SCC had higher ESR values (p = 0.041), higher LY% (p = 0.037), higher NLR (p = 0.041), and lower LMR (p = 0.025). This study provides evidence supporting distinct tumor characteristics and immune response patterns in patients diagnosed with SCC and BSC with a high sun exposure history. These findings imply that sun exposure may contribute to tumor progression and influence the immune response in individuals with SCC and BSC.

Acute mercury poisoning complicated by gastrointestinal bleeding

Mercury poisoning is a rare but potentially serious condition that can result from environmental exposure to elemental mercury. We present a case of a 22-year-young male who presented to the emergency department (ED) with symptoms of mercury poisoning after his family members brought home a vial of elemental mercury. The patient experienced nausea, anxiety, abdominal pain, diarrhea, and fever. Despite normal initial laboratory tests and imaging studies, a presumptive diagnosis of mercury poisoning was made based on the patient's history of exposure and clinical presentation. Although his hospital stay was complicated by passage of blood in stool, possibly lower GI bleed, but treatment with N-acetylcysteine (NAC) was initiated empirically, leading to resolution of symptoms and a favorable outcome. This case highlights the importance of considering mercury poisoning in patients with appropriate exposure history and the effectiveness of NAC in the treatment of acute mercury poisoning. Public education on the hazards of mercury and the importance of prompt recognition and treatment are essential in preventing severe complications associated with mercury exposure.

Ghosts of parasites past influence current non-consumptive effects in Drosophila nigrospiracula

Parasites can indirectly impact hosts through non-consumptive effects (NCEs) via changes in behaviour, morphology, and/or physiology. These responses can be understood in terms of the ecology of fear (ectoparasites) or the ecology of disgust (endoparasites) framework. We tested the hypothesis that NCEs of parasite exposure (e.g., parasite avoidance and defense) trade off with other important behaviours such as feeding and resting. We predicted that when exposed to parasites (without infection), hosts will increase their defensive behaviors at the expense of feeding. We also posited that history of exposure (without infection), or previous infection would impact the expression of these NCEs. The study system involves a cactophilic fruit fly (Drosophila nigrospiracula) and a naturally occurring parasitic mite (Macrocheles subbadius). First, we assessed how prior mite exposure affected fly behaviour in response to current parasite exposure. Mite presence resulted in increased grooming and movement, but exposure history did not affect these behaviours. However, the interaction between previous and current exposure influenced host feeding and resting behaviours. We found that previously exposed flies increased feeding and decreased resting upon a secondary mite exposure. In a second experiment, we tested the role of infection history on current parasite exposure. Compared with naïve flies, previously infected flies were expected to increase defensive behaviours upon secondary exposure. Flies increased defensive and ambulatory behaviour in the presence of mites, and consequently less time was spent resting but feeding was unaffected. None of the behaviours measured were affected by previous infection status. In general, current parasite exposure resulted in NCEs. Moreover, our results showed that previous exposure (without infection) to parasites may have an even stronger effect upon secondary exposure than infection history. Our study highlights the importance of the ecology of fear and the role that exposure and infection history plays in generating NCEs of parasitism.

Staffing and Antipsychotic Medication Use in Nursing Homes and Neighborhood Deprivation

Inappropriate use of antipsychotic medications in nursing homes is a growing public health concern. Residents exposed to higher levels of socioeconomic deprivation in the area around a nursing home may be currently exposed, or have a long history of exposure, to more noise pollution, higher crime rates, and have less opportunities to safely go outside the facility, which may contribute to psychological stress and increased risk of receiving antipsychotic medications inappropriately. However, it is unclear whether neighborhood deprivation is associated with use of inappropriate antipsychotic medications and whether this outcome is different by facility staffing levels. To evaluate whether reported inappropriate antipsychotic medication use differs in severely and less severely deprived neighborhoods, and whether these differences are modified by higher levels of total nurse staffing. This was a cross-sectional analysis of a national sample of nursing homes that linked across 3 national large-scale data sets for the year 2019. Analyses were conducted between April and June 2023. Neighborhood deprivation status (severe vs less severe) and total staffing hours (registered nurse, licensed practical nurse, certified nursing assistant). This study estimated the association between neighborhood deprivation and the percentage of long-stay residents who received an antipsychotic medication inappropriately in the nursing home at least once in the past week and how this varied by nursing home staffing through generalized estimating equations. Analyses were conducted on the facility level and adjusted for state fixed effects. This study included 10 966 nursing homes (1867 [17.0%] in severely deprived neighborhoods and 9099 [83.0%] in less deprived neighborhoods). Unadjusted inappropriate antipsychotic medication use was greater in nursing homes located in severely deprived neighborhoods (mean [SD], 15.9% [10.7%] of residents) than in those in less deprived neighborhoods (mean [SD], 14.2% [8.8%] of residents). In adjusted models, inappropriate antipsychotic medication use was higher in severely deprived neighborhoods vs less deprived neighborhoods (19.2% vs 17.1%; adjusted mean difference, 2.0 [95% CI, 0.35 to 3.71] percentage points) in nursing homes that fell below critical levels of staffing (less than 3 hours of nurse staffing per resident-day). These findings suggest that levels of staffing modify disparities seen in inappropriate antipsychotic medication use among nursing homes located in severely deprived neighborhoods compared with nursing homes in less deprived neighborhoods. These findings may have important implications for improving staffing in more severely deprived neighborhoods.

Radiation Therapy for Non-Melanoma Skin Cancer: A Study of 63 Cases

Cutaneous carcinomas are the most common skin cancers. Our work aims to identify the epidemiological and clinicopathological characteristics of cutaneous carcinomas, especially squamous cell carcinomas and basal cell carcinomas, treated and monitored at the Oncoradiotherapy Department of the Mohammed VI University Hospital of MARRAKECH, treated with radiotherapy, and to evaluate their efficacy and tolerance. Our study is retrospective and descriptive. We collected data from 63 patients treated and monitored between 2019 and 2022 at the Marrakech University Oncohematology Hospital. For each patient, we collected epidemiological, clinicopathological, therapeutic, and evolutionary data using an exploitation form. The age of the patients ranged from 27 to 95 years, with a peak between 61 and 70 years and a median of 64.32. Males predominated (74.6%). The matte skin phenotype was the most common, present in more than half of the patients. Among 63 patients surveyed, 69.8% had a history of prolonged sun exposure. Tumors of the head and neck were found in 65% of cases, with clinical appearance varying: 36.5% ulcerative-budding, 31.7% budding, 22.2% nodular, 6.4% sclerodermiform, and 3.2% ulcerated. Recurrences accounted for only 27% of consultations, and precancerous lesions were found in only 16% of patients. Most patients consulted at locally advanced stages (68.2%). Histologically, squamous cell carcinoma was confirmed in 63.5% of patients. External radiotherapy was performed in all patients, using three-dimensional conformal technique, adjuvant in 77.7% of cases, exclusive definitive in 19%, and palliative in 3.2% of cases. No patient received brachytherapy. Acute complications were observed in 52% of cases and late complications in 8%. After an average follow-up of 2 years, 76% of patients are still being followed in good disease control status with a complete response in 83% of them, 11% local recurrence, and 6% distant metastases. The incidence of cutaneous ........

Pleuroparenchymal fibroelastosis as a late complication of childhood cancer therapy: A case series.

Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial pneumonia with distinct clinicopathologic features. It has been associated with exposure to hematopoietic stem cell transplantation (HSCT) and classical alkylating agents. Here, we highlight PPFE as a late complication of childhood cancer therapy by describing the cases of four survivors of childhood cancer with a diagnosis of treatment-related PPFE. All patients received high-dose alkylating agents. PPFE should be considered in the differential diagnosis of restrictive lung disease in patients with history of exposure to alkylating agents or HSCT. Development of PPFE-specific, noninvasive diagnostic tools and disease-modifying therapies will clinically benefit these patients.

Diffuse Pleural Mesotheliomas with Genomic Near-Haploidization: A Newly Recognized Subset with Distinct Clinical, Histologic, and Molecular Features.

Diffuse pleural mesotheliomas (DPM) with genomic near-haploidization (GNH) represent a novel subtype first recognized by The Cancer Genome Atlas project; however, its clinicopathologic and molecular features remain poorly defined. We analyzed clinical genomic profiling data from 290 patients with DPM using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay. Allele-specific copy number analysis was performed using the Fraction and Allele-Specific Copy Number Estimates from Tumor Sequencing (FACETS) algorithm. A total of 210 patients were evaluable for loss of heterozygosity (LOH) analysis using FACETS from MSK-IMPACT tumor:normal sequencing data. In this cohort, GNH, defined as LOH across >80% of the genome, was detected in 10 cases (4.8%). Compared with non-GNH tumors, GNH DPMs were associated with younger age and less frequent self-reported history of occupational asbestos exposure. Histologically, GNH DPMs were enriched in biphasic subtype (80% vs. 14.5%) and showed abundant tumor-infiltrating lymphocytes (TILs). Genomic analysis revealed a higher frequency of TP53 alterations, whereas SETDB1 mutations were present in nearly all and only in this subset. The clinicopathologic and molecular findings were further validated in a separate cohort. Despite the younger age, patients with GNH DPMs had a shorter overall survival (10.9 vs. 25.4 months, P = 0.004); the poor prognostic impact of GNH remained significant after controlling for biphasic histology. Of three patients with GNH DPMs who received immune checkpoint blockade, two achieved a clinician-assessed partial response. GNH defines an aggressive subtype of mainly biphasic DPMs in younger patients with recurrent alterations in SETDB1 and TP53. The enrichment in biphasic histology and TILs, together with our preliminary immune checkpoint blockade response data and anecdotal clinical trial data, suggests that further evaluation of immunotherapy may be warranted in this subset.

Persistence and evidence for accelerated biodegradation of streptomycin in agricultural soils

Some antibiotics are used for the treatment of various bacterial crop diseases, and there is a concern that this practice may represent a selection pressure that increases the reservoir of antibiotic resistance carried by bacteria in crop production systems. Since the 1950s the aminoglycoside antibiotic streptomycin has been widely used for the treatment of some bacterial crop diseases such as fire blight in apples and pears. Following application, the time that bacteria will be exposed to the antibiotic, and therefore the pressure for selection of resistance, will vary according to the environmental persistence of the antibiotic. In the present study, the dissipation of streptomycin was examined in soils supplemented with 5 mg streptomycin/kg soil and incubated for 21 days under laboratory conditions. The impact of two key rate-controlling variables, soil texture (sandy loam, loam, clay loam) and temperature (4, 20, 30 °C) on streptomycin persistence were explored. -Robust methods for streptomycin extraction and analysis by LC-MS/MS were developed. Streptomycin dissipation followed first order kinetics, with the time to dissipate 50 % of the parent compound (DT50) in soils of varying texture incubated at 20 °C ranging from about seven to 15 days. In contrast, the DT50 of streptomycin in autoclaved loam soil incubated at 20 °C was about 111 days. At 4 °C the DT50 ranged from 49 to 137 days. Under no incubation conditions were any extractable transformation products obtained. Streptomycin was dissipated significantly more rapidly in field soil that had a prior history of exposure to the antibiotic than in soil that did not. Taken together, these results indicate that streptomycin is amenable to biodegradation in agricultural soils with DT50s of several days when temperature is permissive.

Organ involvement in adults with BPDCN is associated with sun exposure history, TET2 and RAS mutations, and survival

AbstractBlastic plasmacytoid dendritic cell neoplasm (BPDCN) can involve skin, bone marrow (BM), central nervous system (CNS), and non-CNS extramedullary sites. Preclinical models demonstrated clonal advantage of TET2-mutated plasmacytoid dendritic cells exposed to UV radiation. However, whether sun exposure, disease characteristics, and patient survival are clinically related is unclear. We classified organ involvement in 66 patients at diagnosis as skin only (n = 19), systemic plus skin (n = 33), or systemic only (n = 14). BM involvement was absent, microscopic (<5%), or overt (≥5%). UV exposure was based on clinical and demographic data. Patients with skin only BPDCN were more frequently aged ≥75 years (47% vs 19%; P = .032) and had lower rates of complex karyotype (0 vs 32%, P = .022) and mutated NRAS (0 vs 29%, P = .044). Conversely, those without skin involvement had lower UV exposure (23% vs 59%, P = .03) and fewer TET2 mutations (33% vs 72%, P = .051). The median overall survival (OS) was 23.5, 20.4, and 17.5 months for skin only, systemic plus skin, and systemic only, respectively. Patients with no BM involvement had better OS vs overt involvement (median OS, 27.3 vs 15.0 months; P = .033) and comparable with microscopic involvement (27.3 vs 23.5 months; P = .6). Overt BM involvement remained significant for OS when adjusted for baseline characteristics and treatment received. In summary, BPDCN clinical characteristics are associated with disease genetics and survival, which together may impact prognosis and indicate informative disease subtypes for future research.

The immunodominance of antigenic site Sb on the H1 influenza virus hemagglutinin increases with high immunoglobulin titers of the cohorts and with young age, but not sex

The head domain of the hemagglutinin of influenza viruses plays a dominant role in the antibody response due to the presence of immunodominant antigenic sites that are the main targets of host neutralizing antibodies. For the H1 hemagglutinin, five major antigenic sites defined as Sa, Sb, Ca1, Ca2, and Cb have been described. Although previous studies have focused on defining the hierarchy of the antigenic sites of the hemagglutinin in different human cohorts, it is still unclear if the immunodominance profile of the antigenic sites might change with the antibody levels of individuals or if other demographic factors (such as exposure history, sex, or age) could also influence the importance of the antigenic sites. The major antigenic sites of influenza viruses hemagglutinins are responsible for eliciting most of the hemagglutination inhibition antibodies in the host. To determine the antibody prevalence towards each major antigenic site, we evaluated the hemagglutination inhibition against a panel of mutant H1 viruses, each one lacking one of the “classic” antigenic sites. Our results showed that the individuals from the Stop Flu NYU cohort had an immunodominant response towards the sites Sb and Ca2 of H1 hemagglutinin. A simple logistic regression analysis of the immunodominance profiles and the hemagglutination inhibition titers displayed by each donor revealed that individuals with high hemagglutination inhibition titers against the wild-type influenza virus exhibited higher probabilities of displaying an immunodominance profile dominated by Sb, followed by Ca2 (Sb > Ca2 profile), while individuals with low hemagglutination inhibition titers presented a higher chance of displaying an immunodominance profile in which Sb and Ca2 presented the same level of immunodominance (Sb = Ca2 profile). Finally, while age exhibited an influence on the immunodominance of the antigenic sites, biological sex was not related to displaying a specific immunodominance profile.

Erasmus syndrome: A rare case report

Erasmus syndrome is a rare clinical entity in which systemic sclerosis develops following exposure to silica with or without development of silicosis. There are very few cases reported in literature from India. Here we report a case of Erasmus syndrome in a 52 years male who is a stone crusher by occupation for last 22 years presented with dry cough, low grade irregular fever, progressive shortness of breath, slowly progressive sclerodactyly and features suggestive of Raynaud’s phenomenon. Radiological evaluations revealed multiple subpleural and centrilobular nodules in bilateral upper, lower lobes and right middle lobe, conglomerated nodular opacities (progressive massive fibrosis- PMF). There was pleural thickening and calcification, bronchial dilatation and fibrosis, calcified right hilar and mediastinal lymphadenopathy. Serological markers like Anti Scl-70 antibody came out to be positive (3+) Based on clinical features diagnosis of systemic sclerosis was made. Based on exposure history and radiology silicosis was diagnosed. Association of silicosis and systemic sclerosis establishes the diagnosis of Erasmus syndrome. Treatment was started with Prednisone, cyclophosphamide and Nifedipine. Strict avoidance to cold and regular follow-up was advised.

A pathway study of factors influencing quality of fertility life

BackgroudTo investigate the factors influencing fertility quality of life in infertile men, constructing a structural equation model of the factors influencing fertility quality of life in infertile men, and to provide suggested measures for improving fertility quality of life in infertile men.MethodsIt is a Observational study. Infertile men (n = 250) attending a fertility centre in a hospital in Xinjiang, matched 1:2 men with no obvious male factor in the control group (n = 500).The Quality of Fertility Life Scale, the Social Support Scale, the Fertility Stress Scale and the Positive Attention Awareness Scale were used to conduct the survey. The model was constructed by applying the maximum likelihood estimation method in Mplus 8.3 software, to explore the factors influencing the quality of reproductive life of infertile men through path analyses. Differences between the case and control groups were statistically significant (P < 0.05) in terms of total fertility quality of life scores, core entry dimensions, affective responses, physical and mental relationships, selective treatment dimensions, and treatment tolerance.ResultsPast medical history, history of exposure to hazardous environments, health insurance reimbursement, social support, fertility stress, and mindfulness are important factors affecting the quality of fertility life of infertile men.ConclusionThe quality of fertility life of infertile men is not optimistic. By improving the level of mindfulness, fertility stress, and social support, we propose appropriate measures to improve the quality of fertility life of infertile men. These measures can improve their confidence in clinical diagnosis and infertility treatment, enabling them to cope positively with these challenges.

Trends and risk factors for drug-resistant tuberculosis among children in Sichuan, China: A 10-year retrospective analysis, 2013-2022.

To investigate the status of the drug-resistant tuberculosis (DR-TB) among children in Sichuan, and to find out the risk factors and high-risk population related to drug resistance among children. The clinical data of tuberculosis patients ≤14 years old with culture-confirmed tuberculosis hospitalized in Chengdu Public Health Clinical Center from January 2013 through December 2022 were collected. Clinical data such as gender, age, ethnicity, history of anti-TB treatment, history of exposure to tuberculosis, nutritional status, and specific drug resistance of the children were collected and recorded. The drug resistance of children in different age groups (0-4 years old, 5-9 years old, 10-14 years old) and different periods (2013-2017 and 2018-2022) were grouped and compared. Logistic regression analysis was to analyze analysis of risk factors of drug resistance in children. A total of 438 children with culture-confirmed tuberculosis were screened. Among them, 26.19% (11/42) were 0 to 4 years old, 33.33% (22/66) were 5 to 9 years old, and 36.67% (121/330) were 10 to 14 years old among the resistant children. There was no statistically significant difference in the resistance rate among the 3 groups (P = .385). The proportions of DR-TB, monoresistant tuberculosis, polydrug-resistant tuberculosis were decreased during 2019 to 2022 compared with 2013 to 2017 (P < .0001). The resistance rates of drug resistant, monoresistant, polydrug-resistant, isoniazid-resistant, and rifampicin resistant during 2018 to 2022 were decreased compared with those from 2013 to 2017 (P < .05), but the multi-drug resistance rate was not decreased (P = .131, without statistical difference). The results of logistic regression analysis showed that male gender OR = 1.566 (95% CI 1.035-2.369), a history of antituberculosis therapy OR = 4.049 (95% CI 1.442-11.367), and pulmonary and extrapulmonary tuberculosis OR = 7.335 (95% CI 1.401-38.392) were risk factors for the development of drug resistance; but fever OR = 0.581 (95% CI 0.355-0.950) was Protective factor. The total drug resistance rate of children in Sichuan showed a downward trend, but the rate of multi-drug-resistant tuberculosis was still at a high level, and the form of drug resistance was still severe. Absence of fever, male, retreatment, and pulmonary concurrent with extrapulmonary tuberculosis are risk factors for DR-TB in children.

Clinical manifestations, antimicrobial resistance and genomic feature analysis of multidrug-resistant Elizabethkingia strains

BackgroundElizabethkingia is emerging as an opportunistic pathogen in humans. The aim of this study was to investigate the clinical epidemiology, antimicrobial susceptibility, virulence factors, and genome features of Elizabethkingia spp.MethodsClinical data from 71 patients who were diagnosed with Elizabethkingia-induced pneumonia and bacteremia between August 2019 and September 2021 were analyzed. Whole-genome sequencing was performed on seven isolates, and the results were compared with a dataset of 83 available Elizabethkingia genomes. Genomic features, Kyoto Encyclopedia of Genes and Genomes (KEGG) results and clusters of orthologous groups (COGs) were analyzed.ResultsThe mean age of the patients was 56.9 ± 20.7 years, and the in-hospital mortality rate was 29.6% (21/71). Elizabethkingia strains were obtained mainly from intensive care units (36.6%, 26/71) and emergency departments (32.4%, 23/71). The majority of the strains were isolated from respiratory tract specimens (85.9%, 61/71). All patients had a history of broad-spectrum antimicrobial exposure. Hospitalization for invasive mechanical ventilation or catheter insertion was found to be a risk factor for infection. The isolates displayed a high rate of resistance to cephalosporins and carbapenems, but all were susceptible to minocycline and colistin. Genomic analysis identified five β-lactamase genes (blaGOB, blaBlaB, blaCME, blaOXA, and blaTEM) responsible for β-lactam resistance and virulence genes involved in stress adaptation (ureB/G, katA/B, and clpP), adherence (groEL, tufA, and htpB) and immune modulation (gmd, tviB, cps4J, wbtIL, cap8E/D/G, and rfbC). Functional analysis of the COGs revealed that “metabolism” constituted the largest category within the core genome, while “information storage and processing” was predominant in both the accessory and unique genomes. The unique genes in our 7 strains were mostly enriched in KEGG pathways related to microRNAs in cancer, drug resistance (β-lactam and vancomycin), ABC transporters, biological metabolism and biosynthesis, and nucleotide excision repair mechanisms.ConclusionThe Elizabethkingia genus exhibits multidrug resistance and carries carbapenemase genes. This study presents a comparative genomic analysis of Elizabethkingia, providing knowledge that facilitates a better understanding of this microorganism.