The development and establishment of a heat inactivated preparation of Mycobacterium tuberculosis (H37Rv) as the first international standard for nucleic acid amplification techniques.

A need to develop an inactivated Mycobacterium tuberculosis (Mtb) preparation, to be used as a DNA standard, as an important and urgent requirement for Tuberculosis (TB) diagnostics standardization was identified in 2018. A candidate material was generated using a heat inactivated culture of Mtb strain H37Rv. A lyophilised preparation was evaluated for its suitability as an International Standard for molecular detection of Mtb DNA in an international collaborative study. Together with the use of quantitative PCR assays and rapid diagnostic tests, this candidate standard was demonstrated to be fit-for-purpose. Based on the results from this collaborative study, it is proposed this lyophilised heat inactivated Mtb preparation (NIBSC code: 20/152) to be established by the World Health Organization Expert Committee on Biological Standardization, as the First WHO International Standard for Mycobacterium tuberculosis (H37Rv) for nucleic acid amplification techniques with an assigned unitage of 6.3 log10 or 2 × 106 International Units per vial. The intended uses of this IS are for calibration of secondary or in-house reference preparations used in the assays for the molecular detection of Mtb DNA. It may also be used for assay validation and monitoring the performance in terms of limit of detection of rapid diagnostic tests.

Estimating excess septicaemia mortality and hospitalisation burden associated with influenza in Hong Kong, 1998 to 2019.

Influenza virus infections can lead to a number of secondary complications, including sepsis. We applied linear regression models to mortality and hospital admission data coded for septicaemia from 1998 to 2019 in Hong Kong, and estimated that septicaemia was associated with an annual average excess mortality rate of 0.23 (95% CI 0.04-0.40) per 100 000 persons per year and an excess septicaemia hospitalisation rate of 1.73 (95% CI 0.94-2.50) per 100 000 persons per year. The highest excess morbidity and mortality was found in older adults and young children, and during influenza A(H3N2) epidemics.

[Re-evaluation of the diagnostic value and optimal cutoff point of captopril challenge test in diagnosis of primary aldosteronism].

Objective: The aim of the present study was to re-evaluate the diagnostic value and optimal cutoff point of captopril challenge test (CCT) in diagnosis of primary aldosteronism (PA). Methods: This is a retrospective study. All patients with a high risk for PA underwent screening test, and then proceeded to CCT and fludrocortisone suppression test (FST) on different days. The FST was used as a reference standard for PA. The plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) were measured with an automated chemiluminescence immunoassay. Random number method was performed in the patients with unilateral primary aldosteronism (UPA), in order to make the proportion of the analyzed UPA in PA was 35%. Receiver operating characteristic (ROC) analyses were performed to compare diagnostic accuracy. Results: A total of 543 patients with 400 PA patients and 143 essential hypertension (EH) patients were enrolled. The diagnostic value of post-CCT PAC was significantly higher than that of the post-CCT plasma aldosterone-renin ratio (ARR), and that of the PAC suppression percentage, respectively. The area under the ROC curve (AUCROC) was 0.86 (0.83, 0.89) for PAC, 0.78 (0.74, 0.82) for ARR, and 0.62 (0.56, 0.67) for the PAC suppression percentage (all P<0.01), respectively. The optimal cutoff point of post-CCT PAC for PA was 110 ng/L, in which the sensitivity and specificity were 73.25% and 79.02%, respectively. The diagnostic efficiency of post-CCT PAC was not improved either in combination with PAC suppression percentage or in combination with post-CCT ARR. Conclusions: CCT is a useful test for the confirmation of PA. PAC level of 110 ng/L at 2 h after 50 mg of captopril is recommended as an optimal cutoff point for the diagnosis of PA.

Confronting COVID-19 in under-resourced, African American neighborhoods: a qualitative study examining community member and stakeholders' perceptions.

OBJECTIVE: The purpose of this study was to examine perceptions of COVID-19 related to prevention, coping, and testing of African American residents in under-resourced communities in Alabama. DESIGN: Guided by the PRECEDE-PROCEED model, virtual focus groups were conducted in five urban and rural Alabama communities using secure Zoom meetings. Community residents and stakeholders (N = 36 total) participated; meetings were audio- and video-recorded, transcribed, and analyzed according to Thematic Analysis. Themes were organized by the PRECEDE portion of the model in Predisposing, Reinforcing, and Enabling barriers and facilitators in three focus areas: prevention, coping, and testing. RESULTS: Prevention barriers included apathy, difficulty with social distancing, lack of information, mixed messages from authority figures, and lack of personal protective equipment (PPE). Prevention facilitators included concerns about contracting COVID-19, clear and consistent messages from trusted sources, contact tracing, and the provision of PPE. Coping barriers included food insecurity, mental health issues, isolation, economic hardships, lack of health care access, and issues with virtual schooling and church services, which were exacerbated by the inability to connect to the internet. Facilitators to coping included religious faith, increased physical activity, and a sense of hope. Testing barriers included misunderstanding, fear, mistrust, testing restrictions, and location of testing sites. Facilitators to testing included incentives, clear information from trusted sources, convenient testing locations, and free tests. CONCLUSION: Gaining community members' perspectives can identify barriers and facilitators to prevention, coping, and testing and potentially improve outcomes. While addressing the social determinants of health (e.g. income, education, medical trust) would be an effective path by which to diminish health disparities related to COVID-19, there is an urgent need to mitigate the spread and severity of COVID-19 in vulnerable populations. Interventions should focus on downstream determinants, such as those emerging from our study.

[Prevalence and clinical characteristics of obstructive sleep apnea in patients with primary hyperaldosteronism].

Objective: To explore the proportion of obstructive sleep apnea (OSA) in primary aldosteronism (PA) in Chinese population and compare the clinical characteristics between PA patients with OSA and those without. Methods: A total of 96 patients diagnosed with PA from September 2015 to November 2018 were recruited in this study. OSA was screened by cardio-respiratory polygraphy. According to the apnea hypopnea index (AHI), the patients were divided into PA with OSA group (AHI ≥5 times) and PA without OSA group (AHI<5 times). Results: Among all patients (96), 69 (71.9%) were with OSA, among them 22 patients (22.9%) were with mild OSA, 17 patients (17.7%) were with moderate OSA and 30 patients (31.3%) were with severe OSA. Compared with the patients without OSA, the patients with OSA were elder, and had higher levels of body mass index (BMI), waist circumference (WC), hip circumference (HC), creatinine (CR) and glycosylated haemoglobin (HbA1c) (P<0.05), but lower concentrations of plasma aldosterone (PAC), supine aldosterone renin concentration ratio(ARR) and the PAC after the diagnosis test (P<0.05). Spearman correlation analyses showed that BMI, WC, HC, CR and HbA1c were positively correlated with AHI (P<0.05), while high-density lipoproteincholesterol (HDL-C), supine-PAC and saline infusion test(SIT)-post PAC were negatively correlated with AHI (P<0.05). Conclusions: The proportion of OSA in PA patients is relatively high (71.9%). Metabolic abnormalities are more common in PA patients with OSA, indicating that screening for OSA should be carried out routinely in PA patients.

[Effect of inhibiting the activity of double-stranded RNA-dependent protein kinase in sepsis mice].

Objective: To observe the effects of 2-aminopurine (2-AP), a double-stranded RNA-dependent protein kinase (PKR) inhibitor, on organ function, plasma inflammatory factor expression and 7 days mortality in sepsis mice induced by cecal ligation puncture (CLP). Methods: Forty specific specific pathogen free C57BL/6 mice were randomly divided into sham group (n=10), CLP group (n=10), CLP+2-AP group (n=10) and 2-AP group (n=10). CLP was used to establish sepsis mice models.Peripheral blood serum was collected 24 hours after operation, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (Cr), blood urea nitrogen (BUN) and inflammatory factors (IL-1ß, IL-10 and TNF-α) were detected; peripheral blood and peritoneal lavage fluid were taken for bacterial clearance detection. Another 60 C57BL/6 mice were selected to observe the 7-day survival rate according to the above groups (n=15). Independent sample t test was used to compare the measurement data between groups. Results: The levels of ALT, AST, Cr and BUN in CLP Group and CLP+2-AP group were significantly higher than those in sham group (all P<0.001). The levels of ALT and AST in CLP+2-AP group were significantly lower than those in CLP Group (t=27.88, 11.33, both P<0.001); the levels of Cr and BUN in CLP+2-AP group were significantly lower than those in CLP Group (t=11.02, 7.15, bothP<0.001). Compared with sham group, the levels of pro-inflammatory (IL-1ß and TNF-α) and anti-inflammatory (IL-10) cytokines in CLP group were significantly higher (all P<0.001); the levels of IL-1ß and IL-10 in CLP+2-AP group were significantly lower (all P<0.001), but the levels of TNF-α in CLP+2-AP group were not significantly lower (P=0.33). The 7-day survival rate was 100% in sham group, 13.3% in CLP+2-AP group, 86.7% in 2-AP group and 20.0% in CLP+2-AP group. Inhibition of PKR activation slightly improved the trend of 7-days survival rate of CLP model mice (analysis by mantel Cox test, χ(2)=0.0012, P=0.97). Conclusion: In sepsis mice model, inhibition of PKR activity can reduce the expression of inflammatory factors in plasma, decrease bacterial load in blood and abdominal cavity, and protect organ function, which could suggest that inhibition of PKR activity has potential application in sepsis treatment.

[Situation analysis of off-label drug use in China].

To introduce current literature reporting situations of the off-label drug use(OLDU) by analyzing relevant literatures published in China, this study comprehensively focused on literatures about OLDU in China in seven Chinese and English databases, then extracted and analyzed the data by different literature types. A total of 667 papers were analyzed. The number of literatures about OLDU data analyzed in hospitals was 325, and the number of clinical studies relating to OLDU was 329, in which case series and case reports were the majority(69.91%). In addition, there were 13 expert consensuses of OLDU and another 56 studies about drug use based on the real-world data characteristics and influencing factors. The number of OLDU data studies has increased year by year. Based on the existing studies, there were more western medicine reports than traditional Chinese medicines, and OLDU types were mainly for over-dosage use. The literatures from OLDU data in hospital were mostly limited to one or several tertiary hospitals in a certain area, and the OLDU types were not uniform. Clinical studies were mainly clinical control trials and case series/reports, but with contradictory reporting results. There were fewer OLDU consensus, and the recommended classification was not uniform. The characteristics and analysis of influencing factors of drug using data in real-world focused on traditional Chinese medicine injections, and the results were not the same. In the future, we shall pay more attention to and strengthen reporting and analysis of OLDU, define study objectives, and unify the content and reporting standards, so as to promote the integrated utilization of OLDU data and reflect real situations in our country.

Contact allergy and allergic contact dermatitis caused by lavender: A retrospective study from an Australian clinic.

BACKGROUND: Lavender is commonly used in aromatherapy and in a broad range of personal and household products. It has been identified as a contact sensitizer, and has been reported to cause allergic contact dermatitis (ACD). OBJECTIVES: To report our experience with contact allergy and ACD caused by lavender, and to raise awareness of lavender as a potential contact allergen. METHOD: A retrospective database review was performed of patients attending patch testing clinics at the Skin and Cancer Foundation, Victoria, Australia, from January 1, 1993 to December 31, 2017. RESULTS: Among the 2178 patients patch tested with lavender over this period, a total of 58 positive reactions were recorded in 49 individuals, giving a positive patch test prevalence for patients tested with lavender of 2.2%. Twenty-seven patients were diagnosed with ACD. The most common sources of exposure to lavender were personal care products and essential oils. Of the patients with ACD, 74% were tested with lavender absolute, with positive results in 90% of cases. CONCLUSION: Lavender is an uncommon cause of ACD but is important to consider, given the potential for exposure through the use of personal care items and essential oils.

Autologous stem-cell transplantation after second-line brentuximab vedotin in relapsed or refractory Hodgkin lymphoma.

Background: We previously demonstrated that brentuximab vedotin (BV) used as second-line therapy in patients with Hodgkin lymphoma is a tolerable and effective bridge to autologous hematopoietic cell transplantation (AHCT). Here, we report the post-AHCT outcomes of patients treated with second-line standard/fixed-dose BV and an additional cohort of patients where positron-emission tomography adapted dose-escalation of second-line BV was utilized. Patients and methods: Patients on the dose-escalation cohort received 1.8 mg/kg of BV intravenously every 3 weeks for two cycles. Patients in complete remission (CR) after two cycles received two additional cycles of BV at 1.8 mg/kg, while patients with stable disease or partial response were escalated to 2.4 mg/kg for two cycles. All patients, regardless of treatment cohort, proceeded directly to AHCT or received additional pre-AHCT therapy at the discretion of the treating physician based on remission status after second-line BV. Results: Of the 20 patients enrolled to the BV dose-escalation cohort, 8 patients underwent BV dose-escalation. BV escalation was well-tolerated, but no patients who were escalated converted to CR. Of 56 evaluable patients treated across cohorts, the overall response rate (ORR) to second-line BV was 75% with 43% CR. Twenty-eight (50%) patients proceeded directly to AHCT without post-BV chemotherapy, and a total of 50 patients proceeded to AHCT. Thirteen patients received consolidative post-AHCT therapy with either radiation, BV, or a PD-1 inhibitor. After AHCT, the 2-year progression-free survival (PFS) and overall survival were 67% and 93%, respectively. The 2-year PFS among patients in CR at the time of AHCT (n = 37) was 71% compared with 54% in patients not in CR (p = 0.12). The 2-year PFS in patients who proceeded to AHCT directly after receiving BV alone was 77%. Conclusions: Second-line BV is an effective bridge to AHCT that produces responses of sufficient depth to provide durable remission in conjunction with AHCT (clinicaltrials.gov: NCT01393717).

Transcriptomic analysis reveals differentially expressed genes associated with wool length in rabbit.

Rabbit fur characteristics are primarily genetically determined traits. We used Illumina high-throughput sequencing technology to assess gene expression in the skin tissues of rabbits derived from a cross between Wanxi Angora rabbits and Rex rabbits, which exhibit differential characteristics of short and long wool respectively, to investigate molecular mechanisms related to wool length determination. To identify key regulatory genes involved in rabbit wool length, genes that were differentially expressed between the long- and short-wool rabbits based on a P-value < 0.05 and log2 |fold change| > 1 were characterized. A total of 798 genes were up-regulated and 523 were down-regulated in the long-wool group compared to expression levels in the short-wool group, and these genes were annotated with GO terms and KEGG pathways, revealing wool-development-related biological functions. The Wnt, Hedgehog and TGF-ß signaling pathways, which are related to cell proliferation, fibroblast proliferation and hair follicle regulation respectively, were identified. The expression levels of eight genes were validated by RT-qPCR. In addition, an interaction network was constructed to show the regulatory relationships among the differentially expressed genes. In this study, we found that FGF5, WNT5A, BMP4 and BMP7 showed significant differential expression between the two groups. These transcriptomic profiling results provide comprehensive gene expression information for improving understanding of the molecular mechanisms involved in the growth and development of rabbit wool.

Three cases of lymphocytic thrombophilic arteritis presenting with an annular eruption.

We describe three patients who presented with a striking erythematous non-blanching annular eruption and features of lymphocytic thrombophilic arteritis (LTA), with a prominent lymphocytic vasculitis involving deep dermal vessels. Lymphocytic inflammation was also evident in the superficial vessels and one patient had small superficial ulcers over the ankle area resembling livedoid vasculopathy (LV). Multiple biopsies demonstrated a persistent absence of neutrophils in the infiltrate consistent with a lymphocytic process. In addition to highlighting the annular morphology as a novel presentation of LTA, these cases suggest a possible relationship between LV and LTA and support the notion that they are distinct from neutrophilic vasculitides such as cutaneous polyarteritis nodosa.

Examining Neighborhood Social Cohesion in the Context of Community-based Participatory Research: Descriptive Findings from an Academic-Community Partnership.

Objective: The purpose of this article is to describe the process of conducting an assessment of neighborhood perceptions and cohesion by a community coalition-academic team created in the context of community-based participatory research (CBPR), to guide the design of locally relevant health initiatives. Methods: Guided by CBPR principles, a collaborative partnership was established between an academic center and a local, urban, underserved neighborhood in Birmingham, Alabama to identify and address community concerns and priorities. A cross-sectional survey was conducted in September 2016 among community residents (N=90) to examine perceptions of neighborhood characteristics, including social cohesion and neighborhood problems. Results: The major concerns voiced by the coalition were violence and lack of neighborhood cohesion and safety. The community survey verified the concerns of the coalition, with the majority of participants mentioning increasing safety and stopping the violence as the things to change about the community and the greatest hope for the community. Furthermore, results indicated residents had a moderate level of perceived social cohesion (mean = 2.87 [.67]). Conclusions: The Mid-South TCC Academic and Community Engagement (ACE) Core successfully partnered with community members and stakeholders to establish a coalition whose concerns and vision for the community matched the concerns of residents of the community. Collecting data from different groups strengthened the interpretation of the findings and allowed for a rich understanding of neighborhood concerns.

Empowering One Community at a Time for Policy, System and Environmental Changes to Impact Obesity.

Objective: This article describes Mayors Mentoring Mayors (3M), an initiative of the Arkansas Coalition for Obesity Prevention (ArCOP), which expanded to five states to become the signature community initiative of the Mid-South Transdisciplinary Collaborative Center (Mid-South TCC) for Health Disparities Research. Methods: The 3M program is an extension of the Growing Healthy Communities (GHC) program, which sought to build capacity within communities to reduce obesity by implementing policy, system and environmental (PSE) changes that support healthy living. GHC where the mayor was involved had the most significant changes toward better health. These mayors were recruited to share their successes, lessons learned, and best practices with their colleagues through a series of Lunch & Learns. Following the GHC and 3M models, a multi-state approach to expand 3M to five additional states was developed. ArCOP partnered with the Mid-South TCC to recruit mayors in the five states. Results: Five Lunch & Learn events were held across Arkansas between March and May 2015, with a total of 98 participants (40 mayors, 37 community leaders, 21 guests). Each regional Lunch & Learn had 1-2 host mayor(s) in attendance, with a total of 9 host mayors. For the 3M regional expansion project, eight GHC Recognition Applications from five states were submitted. Five communities, designated as Emerging, were funded to implement GHC projects. Conclusion: ArCOP successfully engaged mayors, elected officials, and stakeholders who can influence policy across Arkansas as well as in an additional five states in the Mid-South TCC region to implement obesity PSE prevention strategies.

Introduction: Impacting the Social Determinants of Health through a Regional Academic-Community Partnership: The Experience of the Mid-South Transdisciplinary Collaborative Center for Health Disparities Research.

Objective: The purpose of this article is to describe the background and experience of the Academic-Community Engagement (ACE) Core of the Mid-South Transdisciplinary Collaborative Center for Health Disparities Research (Mid-South TCC) in impacting the social determinants of health through the establishment and implementation of a regional academic-community partnership. Conceptual Framework: The Mid-South TCC is informed by three strands of research: the social determinants of health, the socioecological model, and community-based participatory research (CBPR). Combined, these elements represent a science of engagement that has allowed us to use CBPR principles at a regional level to address the social determinants of health disparities. Results: The ACE Core established state coalitions in each of our founding states-Alabama, Louisiana, and Mississippi-and an Expansion Coalition in Arkansas, Tennessee, and Kentucky. The ACE Core funded and supported a diversity of 15 community engaged projects at each level of the socioecological model in our six partner states through our community coalitions. Conclusion: Through our cross-discipline, cross-regional infrastructure developed strategically over time, and led by the ACE Core, the Mid-South TCC has established an extensive infrastructure for accomplishing our overarching goal of investigating the social, economic, cultural, and environmental factors driving and sustaining health disparities in obesity and chronic illnesses, and developing and implementing interventions to ameliorate such disparities.

[Serum procalcitonin in patients with pulmonary infection and central nervous system injury].

Objective: To evaluate the influence of serum procalcitonin in the diagnosis and treatment of pulmonary infection in patients with central nervous system injury. Methods: From October 2014 to February 2017, a retrospective study was performed. A total of 1 852 patients were screened in Department of Intensive Care Unite, First Affiliated Hospital of Sun Yat-sen University.Among them, 173 patients were identified with different kinds of infection. Finally, a total of 42 patients with pulmonary infection were enrolled. The clinical data of patients with pulmonary infection and central nervous system (CNS) injury was collected. A univariate and multivariate regression analysis was performed to study the correlation of serum procalcitonin (PCT) with clinical symptoms and signs of the pulmonary infection, body temperature(T), white blood cell count (WBC), percentage of neutrophils (NEU) and the severity of the pulmonary infection (CPIS). The relationship of serum PCT with type of CNS injury, GCS, and exogenous glucocorticoid was further studied. Results: During the period of pulmonary infection, the peak PCT was 0.83 (0.29, 2.79) µg/L and the CPIS was 5.50 (5.00, 7.00). In 9 of 42 patients, the peak PCT was less than 0.25 µg/L. In 7 of 42 patients, the peak PCT was ranged from 0.25 to 0.5 µg/L. In 12 of 42 patients, PCT was ranged from 0.5 to 2 µg/L. Only 10 patients had a PCT 2-10 µg/L and 4 patients had a PCT more than 10 µg/L. There is no correlation between serum PCT and body temperature, white blood cell, percentage of neutrophils and CPIS. There was no significant differences in patients with PCT<0.5 or ≥0.5 µg/L regarding the body temperature, white blood cell, percentage of neutrophils and CPIS. However, serum PCT in patients with pulmonary infection had independent correlation with the post CNS injury day (ß=0.17, 95% CI (0.02, 0.32), P<0.05). The serum PCT was 1.26 (0.47, 2.7) µg/L and 29.41% patients with a PCT less than 0.5 µg/L within 3 days post CNS injury. Serum PCT level was 0.23 (0.16, 0.39) µg/L, and 77.78% patients with a PCT less than 0.5 µg/L at day 4 to day 7 post-injury. The PCT level was 0.52 (0.33, 1.12) µg/L, and 44.44% patients with a PCT less than 0.5 µg/L at day 8 to day 14. The PCT was 3.26 (2.07, 12.40) µg/L, and no patient with a PCT less than 0.5 µg/L after day 15 post-injury. There were no significant relationship found between serum PCT level and type of the disease and surgery, GCS, and use of exogenous glucocorticoid. Conclusions: Serum PCT had no significant increase and was not able to be used in guiding the antibiotics use in patients with CNS injury and pulmonary infection.

Allergic contact dermatitis to substitute hair dyes in a patient allergic to para-phenylenediamine: Pure henna, black tea and indigo powder.

We report a case of a 50-year-old lady with allergic contact dermatitis to para-phenylenediamine, who in her quest to find a substitute hair dye, subsequently reacted to a number of plant-based hair dyes, including pure henna, black tea and indigo powder respectively. While these substances all contain tannins, testing to possible constituents tannic acid and gallic acid was negative.

Hospitalization Fatality Risk of Influenza A(H1N1)pdm09: A Systematic Review and Meta-Analysis.

During the 2009 influenza pandemic, uncertainty surrounding the severity of human infections with the influenza A(H1N1)pdm09 virus hindered the calibration of the early public health response. The case fatality risk was widely used to assess severity, but another underexplored and potentially more immediate measure is the hospitalization fatality risk (HFR), defined as the probability of death among H1N1pdm09 cases who required hospitalization for medical reasons. In this review, we searched for relevant studies published in MEDLINE (PubMed) and EMBASE between April 1, 2009, and January 9, 2014. Crude estimates of the HFR ranged from 0% to 52%, with higher estimates from tertiary-care referral hospitals in countries with a lower gross domestic product, but in wealthy countries the estimate was 1%-3% in all settings. Point estimates increased substantially with age and with lower gross domestic product. Early in the next pandemic, estimation of a standardized HFR may provide a picture of the severity of infection, particularly if it is presented in comparison with a similarly standardized HFR for seasonal influenza in the same setting.