Transmission of Mycobacterium tuberculosis to Healthcare Personnel Resulting From Contaminated Bone Graft Material, United States, June 2021-August 2022.

A nationwide tuberculosis outbreak linked to a viable bone allograft product contaminated with Mycobacterium tuberculosis was identified in June 2021. Our subsequent investigation identified 73 healthcare personnel with new latent tuberculosis infection following exposure to the contaminated product, product recipients, surgical instruments, or medical waste.

Risk Factors for SARS-CoV-2 Infection Among US Healthcare Personnel, May-December 2020.

To determine risk factors for coronavirus disease (COVID-19) among US healthcare personnel (HCP), we conducted a case-control analysis. We collected data about activities outside the workplace and COVID-19 patient care activities from HCP with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results (cases) and from HCP with negative test results (controls) in healthcare facilities in 5 US states. We used conditional logistic regression to calculate adjusted matched odds ratios and 95% CIs for exposures. Among 345 cases and 622 controls, factors associated with risk were having close contact with persons with COVID-19 outside the workplace, having close contact with COVID-19 patients in the workplace, and assisting COVID-19 patients with activities of daily living. Protecting HCP from COVID-19 may require interventions that reduce their exposures outside the workplace and improve their ability to more safely assist COVID-19 patients with activities of daily living.

Two Clinical Prediction Tools to Improve Tuberculosis Contact Investigation.

BACKGROUND: Efficient contact investigation strategies are needed for the early diagnosis of tuberculosis (TB) disease and treatment of latent TB infections. METHODS: Between September 2009 and August 2012, we conducted a prospective cohort study in Lima, Peru, in which we enrolled and followed 14 044 household contacts of adults with pulmonary TB. We used information from a subset of this cohort to derive 2 clinical prediction tools that identify contacts of TB patients at elevated risk of progressing to active disease by training multivariable models that predict (1) coprevalent TB among all household contacts and (2) 1-year incident TB among adult contacts. We validated the models in a geographically distinct subcohort and compared the relative utilities of clinical decisions based on these tools to existing strategies. RESULTS: In our cohort, 296 (2.1%) household contacts had coprevalent TB and 145 (1.9%) adult contacts developed incident TB within 1 year of index patient diagnosis. We predicted coprevalent disease using information that could be readily obtained at the time an index patient was diagnosed and predicted 1-year incident TB by including additional contact-specific characteristics. The area under the receiver operating characteristic curves for coprevalent TB and incident TB were 0.86 (95% confidence interval [CI], .83-.89]) and 0.72 (95% CI, .67-.77), respectively. These clinical tools give 5%-10% higher relative utilities than existing methods. CONCLUSIONS: We present 2 tools that identify household contacts at high risk for TB disease based on reportable information from patient and contacts alone. The performance of these tools is comparable to biomarkers that are both more costly and less feasible than this approach.

QQS orphan gene regulates carbon and nitrogen partitioning across species via NF-YC interactions.

The allocation of carbon and nitrogen resources to the synthesis of plant proteins, carbohydrates, and lipids is complex and under the control of many genes; much remains to be understood about this process. QQS (Qua-Quine Starch; At3g30720), an orphan gene unique to Arabidopsis thaliana, regulates metabolic processes affecting carbon and nitrogen partitioning among proteins and carbohydrates, modulating leaf and seed composition in Arabidopsis and soybean. Here the universality of QQS function in modulating carbon and nitrogen allocation is exemplified by a series of transgenic experiments. We show that ectopic expression of QQS increases soybean protein independent of the genetic background and original protein content of the cultivar. Furthermore, transgenic QQS expression increases the protein content of maize, a C4 species (a species that uses 4-carbon photosynthesis), and rice, a protein-poor agronomic crop, both highly divergent from Arabidopsis. We determine that QQS protein binds to the transcriptional regulator AtNF-YC4 (Arabidopsis nuclear factor Y, subunit C4). Overexpression of AtNF-YC4 in Arabidopsis mimics the QQS-overexpression phenotype, increasing protein and decreasing starch levels. NF-YC, a component of the NF-Y complex, is conserved across eukaryotes. The NF-YC4 homologs of soybean, rice, and maize also bind to QQS, which provides an explanation of how QQS can act in species where it does not occur endogenously. These findings are, to our knowledge, the first insight into the mechanism of action of QQS in modulating carbon and nitrogen allocation across species. They have major implications for the emergence and function of orphan genes, and identify a nontransgenic strategy for modulating protein levels in crop species, a trait of great agronomic significance.

How much do tumor stage and treatment explain socioeconomic inequalities in breast cancer survival? Applying causal mediation analysis to population-based data.

Substantial socioeconomic inequalities in breast cancer survival persist in England, possibly due to more advanced cancer at diagnosis and differential access to treatment. We aim to disentangle the contributions of differential stage at diagnosis and differential treatment to the socioeconomic inequalities in cancer survival. Information on 36,793 women diagnosed with breast cancer during 2000-2007 was routinely collected by an English population-based cancer registry. Deprivation was determined for each patient according to her area of residence at the time of diagnosis. A parametric implementation of the mediation formula using Monte Carlo simulation was used to estimate the proportion of the effect of deprivation on survival mediated by stage and by treatment. One-third (35 % [23-48 %]) of the higher mortality experienced by most deprived patients at 6 months after diagnosis, and one tenth (14 % [-3 to 31 %]) at 5 years, was mediated by adverse stage distribution. We initially found no evidence of mediation via differential surgical treatment. However, sensitivity analyses testing some of our study limitations showed in particular that up to thirty per cent of the higher mortality in most deprived patients could be mediated by differential surgical treatment. This study illustrates the importance of using causal inference methods with routine medical data and the need for testing key assumptions through sensitivity analyses. Our results suggest that, although effort for earlier diagnosis is important, this would reduce the cancer survival inequalities only by a third. Because of data limitations, role of differential surgical treatment may have been under-estimated.

Down-regulation of miR-150 induces cell proliferation inhibition and apoptosis in non-small-cell lung cancer by targeting BAK1 in vitro.

Non-small-cell lung cancer (NSCLC) is one of the most common causes of cancer-related death. Our investigations show that miR-150 is a typical microRNA that is overexpressed in human NSCLC. We characterized the effects of miR-150 overexpression in NSCLC cells and found that down-regulation of miR-150 expression inhibited cell proliferation and induced cell apoptosis in vitro; additionally, up-regulation of miR-150 levels had the opposite effect on tumor growth and progression. Furthermore, we found that the mechanism of the miR-150 effects on NSCLC cells was associated with alterations in the expression of human BRI1-associated receptor kinase 1 (BAK1). miR-150 may function as an oncogene in NSCLC cells by directly targeting BAK1. Thus, these data highlight a novel molecular interaction between miR-150 and BAK1 and provide a novel strategy for NSCLC therapy via the down-regulation of miR-150 expression.

Insulin resistance in NSCLC: unraveling the link between development, diagnosis, and treatment.

Lung cancer is responsible for the highest number of cancer-related deaths, with non-small cell lung cancer (NSCLC) being the most prevalent subtype. A critical aspect of managing lung cancer is reducing morbidity and mortality rates among NSCLC patients. Identifying high-risk factors for lung cancer and facilitating early diagnosis are invaluable in achieving this objective. Recent research has highlighted the association between insulin resistance and the development of NSCLC, further emphasizing its significance in the context of lung cancer. It has been discovered that improving insulin resistance can potentially inhibit the progression of lung cancer. Consequently, this paper aims to delve into the occurrence of insulin resistance, the mechanisms underlying its involvement in lung cancer development, as well as its potential value in predicting, assessing, and treating lung cancer.

Analysis of genes characterizing chronic thrombosis and associated pathways in chronic thromboembolic pulmonary hypertension.

PURPOSE: In chronic thromboembolic pulmonary hypertension (CTEPH), fibrosis of thrombi in the lumen of blood vessels and obstruction of blood vessels are important factors in the progression of the disease. Therefore, it is important to explore the key genes that lead to chronic thrombosis in order to understand the development of CTEPH, and at the same time, it is beneficial to provide new directions for early identification, disease prevention, clinical diagnosis and treatment, and development of novel therapeutic agents. METHODS: The GSE130391 dataset was downloaded from the Gene Expression Omnibus (GEO) public database, which includes the full gene expression profiles of patients with CTEPH and Idiopathic Pulmonary Arterial Hypertension (IPAH). Differentially Expressed Genes (DEGs) of CTEPH and IPAH were screened, and then Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) functional enrichment analyses were performed on the DEGs; Weighted Gene Co-Expression Network Analysis (WGCNA) to screen the key gene modules and take the intersection genes of DEGs and the key module genes in WGCNA; STRING database was used to construct the protein-protein interaction (PPI) network; and cytoHubba analysis was performed to identify the hub genes. RESULTS: A total of 924 DEGs were screened, and the MEturquoise module with the strongest correlation was selected to take the intersection with DEGs A total of 757 intersecting genes were screened. The top ten hub genes were analyzed by cytoHubba: IL-1B, CXCL8, CCL22, CCL5, CCL20, TNF, IL-12B, JUN, EP300, and CCL4. CONCLUSION: IL-1B, CXCL8, CCL22, CCL5, CCL20, TNF, IL-12B, JUN, EP300, and CCL4 have diagnostic and therapeutic value in CTEPH disease, especially playing a role in chronic thrombosis. The discovery of NF-κB, AP-1 transcription factors, and TNF signaling pathway through pivotal genes may be involved in the disease progression process.

Understanding the Enhanced Catalytic Desulfurization Mechanism: Gas-Phase and Surface Reactions with a CuCeOx Catalyst under Nonthermal Plasma Conditions.

To understand the mechanisms of enhanced catalytic technologies under nonthermal plasma (NTP) conditions, complex surface processes must be assessed. However, the predictive capability of the Langmuir-Hinshelwood (L-H) and Eley-Rideal (E-R) processes is limited by various factors. The present study aimed to clarify the interaction mechanisms between NTP and catalysts in the enhancement process, explore the specific pathways of the enhancement process based on E-R and L-H model validations, and obtain data to support the rational design of NTP-enhanced catalytic processes. We investigated CuCeOx catalysts and SO2 removal reaction as a probing reaction using two enhancement scheme configurations, combined with gas-phase reaction process simulations. During the gas-phase reaction stage of the enhancement process, no significant differences were observed among the different configurations caused by the generation of radicals that were induced by N2 (A3Σu+)-excited species. However, introducing CuCeOx catalysts altered the enhancement process, and the placement of the catalyst influenced the corresponding desulfurization mechanism.

Systematic contact investigation: An essential infection prevention skill to prevent tuberculosis transmission in healthcare settings.

A systematic approach to contact investigations has long been a cornerstone of interrupting the transmission of tuberculosis in community settings. This paper describes the implementation of a systematic 10-step contact investigation within an acute care setting during a multistate outbreak of healthcare-associated tuberculosis. A systematic approach to contact investigations might have applicability to the prevention of other communicable infections within healthcare settings.

Long-term trends in incidence, survival and mortality of primary penile cancer in England.

PURPOSE: Few population-based studies exist of long-term trends in penile cancer. We report incidence and mortality trends in England over the 31 years 1979-2009 and survival trends over the 40 years 1971-2010. METHODS: We calculated annual incidence and mortality rates per 100,000 by age and calendar period. We estimated incidence and mortality rate ratios for cohorts born since 1890, and one- and five-year relative survival (%) by age and deprivation category. RESULTS: A total of 9,690 men were diagnosed with penile cancer during 1979-2009. Age-standardized incidence rates increased by 21 %, from 1.10 to 1.33 per 100,000. Mortality rates fell by 20 % after 1994, from 0.39 to 0.31 per 100,000. Survival analyses included 11,478 men diagnosed during 1971-2010. Five-year relative survival increased from 61.4 to 70.2 %. Five-year survival for men diagnosed 2006-2010 was 77 % for men aged under 60 years and 53 % for men aged 80-99 years. The 8 % difference in five-year survival (66-74 %) between men in the most affluent and most deprived groups was not statistically significant. CONCLUSIONS: The 21 % increase in penile cancer incidence in England since the 1970s may be explained by changes in sexual practice, greater exposure to sexually transmitted oncogenic human papilloma viruses, and decreasing rates of childhood circumcision. Improvement in survival is likely due to advances in diagnostic, staging and surgical techniques. There is a need for public health education and potential preventative strategies to address the increasing incidence.

Is bovine density and ownership associated with human tuberculosis in India?

Zoonotic tuberculosis in humans is caused by infection with bacteria of the Mycobacterium tuberculosis complex acquired from animals, most commonly cattle. India has the highest burden of human tuberculosis in the world and any zoonotic risk posed by tuberculosis in bovines needs to be managed at the source of infection as a part of efforts to end human tuberculosis. Zoonotic tuberculosis in humans can be severe and is clinically indistinguishable from non-zoonotic tuberculosis. As a consequence, zoonotic tuberculosis remains under-recognised and the significance of its contribution to human tuberculosis is poorly understood. This study aimed to explore any association between bovine density, bovine ownership, and human tuberculosis reporting in India using self-reported tuberculosis data in households and officially reported tuberculosis cases while controlling for common confounders for human tuberculosis. We find an association between human tuberculosis reporting, bovine density and bovine ownership in India. Buffalo density was significantly associated with an increased risk of self-reported tuberculosis in households (odds ratio (OR) = 1.23 (95% credible interval (CI): 1.10-1.39) at household level; incidence rate ratio (IRR) = 1.17 (95% CI: 1.04-1.33) at district level), while cattle density (OR = 0.80, 95% CI: 0.71-0.89; IRR = 0.78, 95% CI: 0.70-0.87) and ownership of bovines in households (OR = 0.94, 95% CI: 0.9-0.99; IRR = 0.67, 95% CI: 0.57-0.79) had a protective association with tuberculosis reporting. It is unclear whether this relates to differences in tuberculosis transmission dynamics, or perhaps an association between bovines and other unexplored confounders for tuberculosis reporting in humans. Our study highlights a need for structured surveillance to estimate the prevalence of tuberculosis in cattle and buffaloes, characterisation of Mycobacterium tuberculosis complex species present in bovines and transmission analyses at the human-animal interface to better assess the burden and risk pathways of zoonotic tuberculosis in India.

Human umbilical cord mesenchymal stem cells alleviated TNBS-induced colitis in mice by restoring the balance of intestinal microbes and immunoregulation.

AIMS: Human umbilical cord mesenchymal stem cells (HUMSCs) have been documented to be effective for several immune disorders including inflammatory bowel diseases (IBD). However, it remains unclear how HUMSCs function in regulating immune responses and intestinal flora in the trinitrobenzene sulfonic acid (TNBS)-induced IBD model. MATERIALS AND METHODS: We assessed the regulatory effects of HUMSCs on the gut microbiota, T lymphocyte subpopulations and related immune cytokines in the TNBS-induced IBD model. The mice were divided into the normal, TNBS, and HUMSC-treated groups. The effect of HUMSCs was evaluated by Hematoxylin and Eosin (H&E) staining, fluorescence-activated cell sorting (FACS), and enzyme-linked immunosorbent assay (ELISA) analyses. Metagenomics Illumina sequencing was conducted for fecal samples. KEY FINDINGS: We demonstrated that the disease symptoms and pathological changes in the colon tissues of TNBS-induced colitis mice were dramatically ameliorated by HUMSCs, which improved the gut microbiota and rebalanced the immune system, increasing the abundance of healthy bacteria (such as Lactobacillus murinus and Lactobacillus johnsonii), the Firmicutes/Bacteroidetes ratio, and the proportion of Tregs; the Th1/Th17 ratio was decreased. Consistently, the expression levels of IFN-γ and IL-17 were significantly decreased, and transforming growth factor-ß1 (TGF-ß1) levels were significantly increased in the plasma of colitis mice HUMSC injection. SIGNIFICANCE: Our experiment revealed that HUMSCs mitigate acute colitis by regulating the rebalance of Th1/Th17/Treg cells and related cytokines and remodeling the gut microbiota, providing potential future therapeutic targets in IBD.

Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) outbreak investigation in a hospital emergency department-California, December 2020-January 2021.

We describe a large outbreak of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) involving an acute-care hospital emergency department during December 2020 and January 2021, in which 27 healthcare personnel worked while infectious, resulting in multiple opportunities for SARS-CoV-2 transmission to patients and other healthcare personnel. We provide recommendations for improving infection prevention and control.

Keeping health care linens clean: Underrecognized hazards and critical control points to avoid contamination of laundered health care textiles.

Outbreaks of health care-associated infections, particularly invasive mold infections, have been linked to environmental contamination of laundered health care textiles. Contamination may occur at the laundry or health care facility. This report highlights underrecognized hazards, control points, and actions that infection preventionists can take to help decrease the potential for patient exposure to contaminated health care textiles. Infection preventionists can use the checklists included in this report to assess laundry and health care facility management of laundered health care textiles.

A novel promising diagnosis model for colorectal advanced adenoma and carcinoma based on the progressive gut microbiota gene biomarkers.

BACKGROUND: Colorectal cancer (CRC), a commonly diagnosed cancer often develops slowly from benign polyps called adenoma to carcinoma. Altered gut microbiota is implicated in colorectal carcinogenesis. It is warranted to find non-invasive progressive microbiota biomarkers that can reflect the dynamic changes of the disease. This study aimed to identify and evaluate potential progressive fecal microbiota gene markers for diagnosing advanced adenoma (AA) and CRC. RESULTS: Metagenome-wide association was performed on fecal samples from different cohorts of 871 subjects (247 CRC, 234 AA, and 390 controls). We characterized the gut microbiome, identified microbiota markers, and further constructed a colorectal neoplasms classifier in 99 CRC, 94 AA, and 62 controls, and validated the results in 185 CRC, 140 AA, and 291 controls from 3 independent cohorts. 21 species and 277 gene markers were identified whose abundance was significantly increased or decreased from normal to AA and CRC. The progressive gene markers were distributed in metabolic pathways including amino acid and sulfur metabolism. A diagnosis model consisting of four effect indexes was constructed based on the markers, the sensitivities of the Adenoma Effect Index 1 for AA, Adenoma Effect Index 2 for high-grade dysplasia (HGD) adenoma were 71.3% and 76.5%, the specificities were 90.5% and 90.3%, respectively. CRC Effect Index 1 for all stages of CRC and CRC Effect Index 2 for stage III-IV CRC to predict CRC yielded an area under the curve (AUC) of 0.839 (95% CI 0.804-0.873) and 0.857 (95% CI 0.793-0.921), respectively. Combining with fecal immunochemical test (FIT) significantly improved the sensitivity of CRC Effect Index 1 and CRC Effect Index 2 to 96.7% and 100%. CONCLUSIONS: This study reports the successful diagnosis model establishment and cross-region validation for colorectal advanced adenoma and carcinoma based on the progressive gut microbiota gene markers. The results suggested that the novel diagnosis model can significantly improve the diagnostic performance for advanced adenoma.

Investigation of a Prolonged and Large Outbreak of Healthcare-Associated Mucormycosis Cases in an Acute Care Hospital-Arkansas, June 2019-May 2021.

Background: Outbreaks of healthcare-associated mucormycosis (HCM), a life-threatening fungal infection, have been attributed to multiple sources, including contaminated healthcare linens. In 2020, staff at Hospital A in Arkansas alerted public health officials of a potential HCM outbreak. Methods: We collected data on patients at Hospital A who had invasive mucormycosis during January 2017-June 2021 and calculated annual incidence of HCM (defined as mucormycosis diagnosed within ≥7 days after hospital admission). We performed targeted environmental assessments, including linen sampling at the hospital, to identify potential sources of infection. Results: During the outbreak period (June 2019-June 2021), 16 patients had HCM; clinical features were similar between HCM patients and non-HCM patients. Hospital-wide HCM incidence (per 100 000 patient-days) increased from 0 in 2018 to 3 in 2019 and 6 in 2020. For the 16 HCM patients, the most common underlying medical conditions were hematologic malignancy (56%) and recent traumatic injury (38%); 38% of HCM patients died in-hospital. Healthcare-associated mucormycosis cases were not epidemiologically linked by common procedures, products, units, or rooms. At Hospital A and its contracted offsite laundry provider, suboptimal handling of laundered linens and inadequate environmental controls to prevent mucormycete contamination were observed. We detected Rhizopus on 9 (9%) of 98 linens sampled at the hospital, including on linens that had just arrived from the laundry facility. Conclusions: We describe the largest, single-center, HCM outbreak reported to date. Our findings underscore the importance of hospital-based monitoring for HCM and increased attention to the safe handling of laundered linens.

Nationwide tuberculosis outbreak in the USA linked to a bone graft product: an outbreak report.

BACKGROUND: Mycobacterium tuberculosis transmission through solid organ transplantation has been well described, but transmission through transplanted tissues is rare. We investigated a tuberculosis outbreak in the USA linked to a bone graft product containing live cells derived from a single deceased donor. METHODS: In this outbreak report, we describe the management and severity of the outbreak and identify opportunities to improve tissue transplant safety in the USA. During early June, 2021, the US Centers for Disease Control and Prevention (CDC) worked with state and local health departments and health-care facilities to locate and sequester unused units from the recalled lot and notify, evaluate, and treat all identified product recipients. Investigators from CDC and the US Food and Drug Administration (FDA) reviewed donor screening and tissue processing. Unused product units from the recalled and other donor lots were tested for the presence of M tuberculosis using real-time PCR (rt PCR) assays and culture. M tuberculosis isolates from unused product and recipients were compared using phylogenetic analysis. FINDINGS: The tissue donor (a man aged 80 years) had unrecognised risk factors, symptoms, and signs consistent with tuberculosis. Bone was procured from the deceased donor and processed into 154 units of bone allograft product containing live cells, which were distributed to 37 hospitals and ambulatory surgical centres in 20 US states between March 1 and April 2, 2021. From March 3 to June 1, 2021, 136 (88%) units were implanted into 113 recipients aged 24-87 years in 18 states (some individuals received multiple units). The remaining 18 units (12%) were located and sequestered. 87 (77%) of 113 identified product recipients had microbiological or imaging evidence of tuberculosis disease. Eight product recipients died 8-99 days after product implantation (three deaths were attributed to tuberculosis after recognition of the outbreak). All 105 living recipients started treatment for tuberculosis disease at a median of 69 days (IQR 56-81) after product implantation. M tuberculosis was detected in all eight sequestered unused units tested from the recalled donor lot, but not in lots from other donors. M tuberculosis isolates from unused product and recipients were more than 99·99% genetically identical. INTERPRETATION: Donor-derived transmission of M tuberculosis via bone allograft resulted in substantial morbidity and mortality. All prospective tissue and organ donors should be routinely assessed for tuberculosis risk factors and clinical findings. When these are present, laboratory testing for M tuberculosis should be strongly considered. FUNDING: None.

Grape seed proanthocyanidin extract attenuates airway inflammation and hyperresponsiveness in a murine model of asthma by downregulating inducible nitric oxide synthase.

Allergic asthma is characterized by hyperresponsiveness and inflammation of the airway with increased expression of inducible nitric oxide synthase (iNOS) and overproduction of nitric oxide (NO). Grape seed proanthocyanidin extract (GSPE) has been proved to have antioxidant, antitumor, anti-inflammatory, and other pharmacological effects. The purpose of this study was to examine the role of GSPE on airway inflammation and hyperresponsiveness in a mouse model of allergic asthma. BALB/c mice, sensitized and challenged with ovalbumin (OVA), were intraperitoneally injected with GSPE. Administration of GSPE remarkably suppressed airway resistance and reduced the total inflammatory cell and eosinophil counts in BALF. Treatment with GSPE significantly enhanced the interferon (IFN)- γ level and decreased interleukin (IL)-4 and IL-13 levels in BALF and total IgE levels in serum. GSPE also attenuated allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells in the airway. The elevated iNOS expression observed in the OVA mice was significantly inhibited by GSPE. In conclusion, GSPE decreases the progression of airway inflammation and hyperresponsiveness by downregulating the iNOS expression, promising to have a potential in the treatment of allergic asthma.