Pulmonary tuberculosis in two preterm infants conceived by in vitro fertilization.

The early diagnosis of tuberculosis (TB) in infants is challenging owing to the non-specific clinical manifestations in infancy, particularly preterm infants. Two cases in preterm infants are reported. Case 1, conceived by in vitro fertilization (IVF), was born at 27 + 1 weeks gestational age weighing 880 g. He presented on Day 85 with intermittent fever. Following a course of systemic broadspectrum antibiotics, he deteriorated, developing acute respiratory distress syndrome (ARDS). TB Xpert polymerase chain reaction (PCR) of the sputum obtained by laryngeal aspiration confirmed Mycobacterium TB (MTB) on Day 97. He responded well to anti-tuberculosis treatment. His mother had a fever and headache and was diagnosed with COVID-19 79 days after delivery. The fever persisted for nearly 10 days after empirical treatment. She was eventually diagnosed with miliary TB and tuberculous meningitis 92 days after delivery. Case 2 was conceived by IVF and born at 36 + 6 weeks gestation weighing 2430 g. She presented on Day 15 with intermittent fever and abdominal distention. Chest and abdominal radiography demonstrated severe diffuse inflammatory changes. She had received BCG vaccination, and there was no history of contact with active TB. TB PCR of the sputum obtained by laryngeal aspiration confirmed MTB on Day 19. The asymptomatic mother was subsequently diagnosed with pulmonary and genital TB. TB should be considered as a differential diagnosis in infants with unexpected respiratory distress and fever. Women evaluated for infertility should be routinely screened for TB before receiving assisted reproductive treatment, particularly where TB is prevalent.Abbreviations: ARDS: acute respiratory distress syndrome; BPD: bronchopulmonary dysplasia; CPAP: continuous positive airway pressure; CSF: cerebrospinal fluid; HIV: human immunodeficiency virus; IVF: in vitro fertilization; KMC: Kangaroo mother care; MDR: multidrug-resistant; MTB: Mycobacterium tuberculosis; NICU: neonatal intensive care unit; PCR: polymerase chain reaction; PS: pulmonary surfactant; SIMV: synchronised intermittent mandatory ventilation; TB: tuberculosis; CT: computed tomography; HREZ: isoniazid, rifampin, ethambutol and pyrazinamide; IGRA: interferon-γ release assay; IVF: in vitro fertilization; PCR: polymerase chain reaction; TB: tuberculosis.

Comparative analysis of genomic characteristics and immune response between Mycobacterium tuberculosis strains cultured continuously for 25 years and H37Rv.

Tuberculosis (TB) continues to pose a significant global health challenge, emphasizing the critical need for effective preventive measures. Although many studies have tried to develop new attenuated vaccines, there is no effective TB vaccine. In this study, we report a novel attenuated Mycobacterium tuberculosis (M. tb) strain, CHVAC-25, cultured continuously for 25 years in the laboratory. CHVAC-25 exhibited significantly reduced virulence compared to both the virulent H37Rv strain in C57BL/6J and severe combined immunodeficiency disease mice. The comparative genomic analysis identified 93 potential absent genomic segments and 65 single nucleotide polymorphic sites across 47 coding genes. Notably, the deletion mutation of ppsC (Rv2933) involved in phthiocerol dimycocerosate synthesis likely contributes to CHVAC-25 virulence attenuation. Furthermore, the comparative analysis of immune responses between H37Rv- and CHVAC-25-infected macrophages showed that CHVAC-25 triggered a robust upregulation of 173 genes, particularly cytokines crucial for combating M. tb infection. Additionally, the survival of CHVAC-25 was significantly reduced compared to H37Rv in macrophages. These findings reiterate the possibility of obtaining attenuated M. tb strains through prolonged laboratory cultivation, echoing the initial conception of H37Ra nearly a century ago. Additionally, the similarity of CHVAC-25 to genotypes associated with attenuated M. tb vaccine positions it as a promising candidate for TB vaccine development.

Quantitative analysis of the lysine acetylome reveals the role of SIRT3-mediated HSP60 deacetylation in suppressing intracellular Mycobacterium tuberculosis survival.

Protein acetylation and deacetylation are key epigenetic modifications that regulate the initiation and development of several diseases. In the context of infection with Mycobacterium tuberculosis (M. tb), these processes are essential for host-pathogen interactions and immune responses. However, the specific effects of acetylation and deacetylation on cellular functions during M. tb infection are not fully understood. This study employed Tandem Mass Tag (TMT) labeling for quantitative proteomic profiling to examine the acetylproteome (acetylome) profiles of noninfected and M. tb-infected macrophages. We identified 715 acetylated peptides from 1,072 proteins and quantified 544 lysine acetylation sites (Kac) in 402 proteins in noninfected and M. tb-infected macrophages. Our research revealed a link between acetylation events and metabolic changes during M. tb infection. Notably, the deacetylation of heat shock protein 60 (HSP60), a key chaperone protein, was significantly associated with this process. Specifically, the deacetylation of HSP60 at K96 by sirtuin3 (SIRT3) enhances macrophage apoptosis, leading to the elimination of intracellular M. tb. These findings underscore the pivotal role of the SIRT3-HSP60 axis in the host immune response to M. tb. This study offers a new perspective on host protein acetylation and suggests that targeting host-directed therapies could be a promising approach for tuberculosis immunotherapy. IMPORTANCE: Protein acetylation is crucial for the onset, development, and outcome of tuberculosis (TB). Our study comprehensively investigated the dynamics of lysine acetylation during M. tb infection, shedding light on the intricate host-pathogen interactions that underlie the pathogenesis of tuberculosis. Using an advanced quantitative lysine proteomics approach, different profiles of acetylation sites and proteins in macrophages infected with M. tb were identified. Functional enrichment and protein-protein network analyses revealed significant associations between acetylated proteins and key cellular pathways, highlighting their critical role in the host response to M. tb infection. Furthermore, the deacetylation of HSP60 and its influence on macrophage-mediated clearance of M. tb underscore the functional significance of acetylation in tuberculosis pathogenesis. In conclusion, this study provides valuable insights into the regulatory mechanisms governing host immune responses to M. tb infection and offers promising avenues for developing novel therapeutic interventions against TB.

The incremental value of Mycobacterium tuberculosis trace nucleic acid detection in CT-guided percutaneous biopsy needle rinse solutions for the diagnosis of tuberculosis.

Introduction: Tuberculosis (TB) diagnosis still faces challenges with high proportion of bacteriologic test negative incidences worldwide. We assessed the diagnostic value of digital PCR (dPCR) analysis of ultramicro Mycobacterium tuberculosis (M.tb) nucleic acid in CT-guided percutaneous biopsy needle rinse solution (BNRS) for TB. Methods: BNRS specimens were consecutively collected and total DNA was purified. The concentrations of M.tb-specific IS6110 and IS1081 were quantified using droplet dPCR. The diagnostic performances of BNRS-dPCR and its sensitivity in comparison with conventional tests were analyzed. Results: A total of 106 patients were enrolled, 63 of whom were TB (48 definite and 15 clinically suspected TB) and 43 were non-TB. The sensitivity of BNRS IS6110 OR IS1081-dPCR for total, confirmed and clinically suspected TB was 66.7%, 68.8% and 60.0%, respectively, with a specificity of 97.7%. Its sensitivity was higher than that of conventional etiological tests, including smear microscopy, mycobacterial culture and Xpert using sputum and BALF samples. The positive detection rate in TB patients increased from 39.3% for biopsy AFB test alone to 73.2% when combined with BNRS-dPCR, and from 71.4% for biopsy M.tb molecular detection alone to 85.7% when combined with BNRS-dPCR. Conclusion: Our results preliminarily indicated that BNRS IS6110 OR IS1081-dPCR is a feasible etiological test, which has the potential to be used as a supplementary method to augment the diagnostic yield of biopsy and improve TB diagnosis.

Cigarette excise tax structure and cigarette prices in nine sub-Saharan African countries: evidence from the Global Adult Tobacco Survey.

BACKGROUND: Economic theory predicts that the excise tax structure influences the distribution of cigarette prices. Evidence shows that uniform specific excise tax structures exhibit the least price variability relative to other tax structures. The distribution of cigarette prices under different excise tax structures has never been examined for a group of African countries. OBJECTIVES: To examine the distribution of cigarette prices under different tax structures in nine African countries and to critically evaluate the effectiveness of African regional tax directives in promoting public health. METHODS: Data from the Global Adult Tobacco Survey, conducted in eight African countries during 2012-2018, and data from the 2017 Gambia Tobacco Survey were used to construct survey-derived cigarette prices. The coefficients of variation and skewness of the price distribution were compared in the context of each country's cigarette excise tax structure. RESULTS: The least price variability is found in countries with a uniform specific tax, or a mixed system with a minimum specific floor. Cigarette price variability is largest in countries with uniform ad valorem tax structures. Three of the four countries with ad valorem tax structures are in regional blocs, where the tax directives specify that they should implement an ad valorem structure. CONCLUSIONS: Regional tax directives that require the adoption of uniform specific excise taxes, or high minimum specific floors, could be an efficient way to get multiple African countries to adopt a tax structure that reduces substitution possibilities in response to excise tax increases.

A Femoral Neck Osteotomy for the Patients with Ankylosing Spondylitis and Thoracolumbar Kyphosis Combined with Hip Flexion Contracture.

OBJECTIVE: The surgical treatment of patients with ankylosing spondylitis and severe thoracolumbar kyphosis combined with hip flexion contracture is very difficult for all the surgeons. The femoral neck osteotomy (FNO) is the first step to break the ice. The evaluation of a new modified FNO method is very important to improve the curative effect. METHODS: Five male patients with nine bone-fused hips who underwent the new femoral neck osteotomy were included from October 2021 to March 2022. The FNO was designed that the saw blade was manipulated from the lateral femoral neck base to the inferior part of the femoral head, keeping Pauwels' angle less than 30° on the coronal plane. On the transverse plane, the angle between the saw blade and the coronal plane was more than 15°. On the sagittal plane, the saw blade cut through the femoral neck. They accepted pedicle subtraction osteotomy (PSO) after FNO according to the patient' recovery. Then, 2 weeks later, the patients underwent total hip arthroplasty (THA). The visual analogue scale (VAS), Harris hip score (HHS) and passive hip flexion-extension range of motion (ROM) were used to evaluate hip function. The data were analyzed by paired t-test. RESULTS: The average operation time and blood loss of FNO, the average interval between FNO and THA were collected. The average angle of the trunk and lower limb (ATL) was 36.33° ± 16.36° pre-FNO, 82.89° ± 13.51° post-FNO and 175.22° ± 3.42° post-THA. The average VAS scores were 0 pre-FNO, 5 ± 1.58 post-FNO and 2.6 ± 0.55 post-THA. The average HHS was 43.56 ± 1.59 preoperatively and 83.89 ± 2.21 postoperatively. The average hip extension ROM was 23.89° ± 12.69° pre-FNO, -22.67° ± 14.18° post-FNO and - 3.33° ± 2.50 post-THA°. The average hip flexion ROM was 23.89° ± 12.69° pre-FNO, 35.56° ± 12.11° post-FNO and 104.44° ± 5.27° post-THA. The differences among them were significant (p < 0.05). Only one hip (11.11%) displaced completely after FNO. CONCLUSION: A new modified FNO was developed, which can provide osteotomy with a certain degree of stability and greater ease for performing PSO and THA.

Prevalence and Covariates of Electronic Cigarette Use among Students Aged 13-15 Years in the Philippines: 2019 Global Youth Tobacco Survey.

Electronic cigarette use is growing in popularity and accessibility among youth in the Southeast Asia region. We analyzed data on 6670 students, aged 13-15 years, from the Philippines' 2019 Global Youth Tobacco Survey. Prevalence estimates and 95% confidence intervals (CI) were estimated for current use (i.e., past 30 days), ever use, and awareness of e-cigarettes. Chi-square tests compared prevalence differences between groups. Multiple logistic regression models assessed factors associated with e-cigarette use while controlling for sociodemographic characteristics, current use of other tobacco products, and secondhand smoke exposure. Prevalence of current e-cigarette use was 14.1% (95% CI = 12.4%, 15.8%), ever use was 24.6% (95% CI = 22.4%, 26.9%), and awareness was 75.5% (95% CI = 73.0%, 78.0%). Current use of any other tobacco products and exposure to secondhand smoke at home, school, or other public places were positively associated with current and ever use of e-cigarettes. Boys and youth living in Luzon or Mindanao had higher odds of current e-cigarette use compared to girls and youth in Visayas. Findings indicated that one in four Philippine students aged 13-15 years ever used e-cigarettes and one in seven currently use e-cigarettes. This study highlights the importance of implementing evidence-based strategies, including relevant tobacco control policies.

Reduction quality in lateral view of X-ray and hypoalbuminemia are associated with postoperative mortality in elderly pertrochanteric fracture patients.

Background: Pertrochanteric fracture is one of the most prevalent public health issues across the world for the elderly population. The purpose of this study was to investigate the association between surgical factors and postoperative mortality in patients with intramedullary nail-treated pertrochanteric fractures. Methods: A retrospective cohort study was designed to evaluate the pertrochanteric fracture patients treated with intramedullary nail between January 2016 to February 2021. The surgical factors included the Dorr morphology, Arbeitsgemeinschaft für Osteosynthesefragen/Orthopedic Trauma Association (AO/OTA) classification of fractures, the tip-apex distance (TAD), location of the cephalic screw, reduction quality in anterior-posterior (AP) and lateral views, the integrity of the lateral wall, and the design of cephalic screws. Using univariate and multivariate Cox proportional hazard models, the association between these risk factors and postoperative mortality in patients with this type of fractures was evaluated. Results: A total of 169 pertrochanteric fracture patients treated with intramedullary nails were included in our study, with the average age of 82.68±5.93 years. The mortality rates at 3 months, 1 year, and the end of follow-up were 4.14%, 11.24%, and 26.04%, respectively. According to the univariate Cox analysis, age, gender, preoperative levels of hemoglobin (Hb) and albumin (Alb) were associated with a poor overall survival (OS) (P<0.05). After multivariate adjustment, the pre-operative level of Alb (P<0.001) and the reduction in lateral view (P<0.001) were shown to be independent risk factors for poor OS. Conclusions: The preoperative hypoalbuminemia and reduction quality in lateral view were associated with postoperative mortality in our study. Therefore, optimizing both parameters could improve the prognosis in elderly pertrochanteric fracture patients.

The role of Mycobacterium tuberculosis acetyltransferase and protein acetylation modifications in tuberculosis.

Tuberculosis (TB) is a widespread infectious disease caused by Mycobacterium tuberculosis (M. tb), which has been a significant burden for a long time. Post-translational modifications (PTMs) are essential for protein function in both eukaryotic and prokaryotic cells. This review focuses on the contribution of protein acetylation to the function of M. tb and its infected macrophages. The acetylation of M. tb proteins plays a critical role in virulence, drug resistance, regulation of metabolism, and host anti-TB immune response. Similarly, the PTMs of host proteins induced by M. tb are crucial for the development, treatment, and prevention of diseases. Host protein acetylation induced by M. tb is significant in regulating host immunity against TB, which substantially affects the disease's development. The review summarizes the functions and mechanisms of M. tb acetyltransferase in virulence and drug resistance. It also discusses the role and mechanism of M. tb in regulating host protein acetylation and immune response regulation. Furthermore, the current scenario of isoniazid usage in M. tb therapy treatment is examined. Overall, this review provides valuable information that can serve as a preliminary basis for studying pathogenic research, developing new drugs, exploring in-depth drug resistance mechanisms, and providing precise treatment for TB.

Changes in Tobacco Product Use Among Students Aged 13 to 15 Years in 34 Countries, Global Youth Tobacco Survey, 2012-2020.

INTRODUCTION: Most adults who currently use tobacco start before age 21. Comprehensive, cost-effective strategies and interventions to prevent initiation and encourage tobacco use cessation among youth are critical aspects of protecting youth from the harms of commercial tobacco. We describe changes in current tobacco product use among youth in 34 sites using data from the Global Youth Tobacco Survey (GYTS). METHODS: GYTS is a nationally representative school-based survey of students aged 13 to 15 years. The analysis included 34 sites that completed 2 survey waves during 2012-2020. Prevalence of current tobacco use was assessed for each country. Marginal effects in multivariable logistic regression models were used to estimate adjusted prevalence difference (aPD) between waves. RESULTS: The adjusted prevalence of current tobacco product use remained unchanged in more than 60% of the included sites. For any tobacco use, significant decreases were reported for Bhutan (aPD = -8.1; 95% CI, -12.9 to -3.4), Micronesia (aPD = -7.2; 95% CI, -9.7 to -4.7), San Marino (aPD = -7.0; 95% CI, -11.2 to -2.7), Togo (aPD = -2.7; 95% CI, -4.6 to -0.7), and Panama (aPD = -2.2; 95% CI, -4.1 to -0.4); significant increases were reported for Moldova, Albania, and Paraguay. Current e-cigarette use increased significantly in 7 of 10 sites. CONCLUSION: Data show that progress toward reducing tobacco use among youth stalled during 2012-2020, while e-cigarette use increased in a few sites with available data.

Reasons to decrease or stop nicotine and tobacco use among adults and association with MPOWER scores in twenty-one middle- and high-income countries, 2019-2020.

INTRODUCTION: This study examined reasons why people planned to reduce or stop tobacco consumption and their relationship with MPOWER scores, adjusting for sociodemographic, cultural, and economic factors. METHODS: Data used were Euromonitor International's Voice of the Consumer: Nicotine Survey 2019-2020, World Bank's country income and WHO's MPOWER policy scores. Analytical sample included 21913 adults of legal smoking age in 21 middle- and high-income countries who used nicotine and tobacco products and planned to reduce or stop their consumption in the next 12 months. Poisson regression models with robust error variance, adjusted for sociodemographic and tobacco use covariables, generated adjusted risk ratios (ARRs) of selecting a certain reason to reduce tobacco consumption dependent on continuous MPOWER scores. RESULTS: Main reasons to reduce or stop tobacco consumption were improving health (85%), saving money (65%), pressure from family (19%), and using another substance instead (4%). Country variation was observed by MPOWER scores. Positive associations were found between some MPOWER scores and reasons to reduce or stop tobacco consumption: enforcing bans on tobacco advertising and using another substance (ARR=1.28; 95% CI: 1.11-1.47); warning about dangers of tobacco and saving money (ARR=1.25; 95% CI: 1.19-1.32); offering help to quit tobacco and using another substance (ARR=1.26; 95% CI: 1.10-1.45) or family pressure (ARR=1.11; 95% CI: 1.04-1.17); anti-tobacco campaigns and using another substance (ARR=1.15; 95% CI: 1.08-1.23); and raising taxes and saving money (ARR=1.11; 95% CI: 1.09-1.13). CONCLUSIONS: MPOWER scores are associated with reported reasons to quit tobacco including to improve health, save money, respond to family pressure or use another substance instead.

A Higher Postoperative Barthel Index at Discharge is Associated with a Lower One-Year Mortality After Hip Fracture Surgery for Geriatric Patients: A Retrospective Case‒Control Study.

Purpose: To evaluate the relationship between the postoperative Barthel index assessing activities of daily living at discharge and the one-year mortality after hip fracture surgery. Methods: Patients with hip fracture admitted to Peking University First Hospital from January 2015 to January 2020 were enrolled retrospectively according to the inclusion and exclusion criteria. The Barthel index and other related confounding variables were collected. Logistic regression and Kaplan‒Meier survival curves were constructed to explore the relationship between the postoperative Barthel index at discharge and the one-year mortality of geriatric patients after hip fracture surgery. Results: A total of 444 patients with a mean age of 81.61±6.14 years were included. A significant difference was not observed in the preoperative Barthel index at admission between the deceased group and the surviving group (38.90±15.83 vs 36.96±10.74, p=0.446). However, the difference in the postoperative Barthel index at discharge between these two groups was statistically significant (43.08±14.40 vs 53.18±13.43, P<0.001). The multivariable logistic regression analysis revealed that the postoperative Barthel index at discharge was an independent risk factor for one-year mortality after adjustment for confounding variables (adjusted OR 0.73, 95% CI 0.55-0.98, p˂0.05). The Kaplan‒Meier survival curve showed that patients who had a high Barthel index (≥50) at discharge had a significantly lower mortality in the long term than patients with a low Barthel index (<50) at discharge (P< 0.001). Conclusion: The postoperative Barthel index at discharge was independently associated with the one-year mortality of geriatric patients after hip fracture surgery. A higher postoperative Barthel index at discharge indicated a lower mortality after hip fracture surgery. The Barthel index at discharge has the potential to provide essential prognostic information for early risk stratification and directing future care.

Targeting breast cancer stem cells directly to treat refractory breast cancer.

For patients with refractory breast cancer (BC), integrative immunotherapies are emerging as a critical component of treatment. However, many patients remain unresponsive to treatment or relapse after a period. Different cells and mediators in the tumor microenvironment (TME) play important roles in the progression of BC, and cancer stem cells (CSCs) are deemed the main cause of relapse. Their characteristics depend on their interactions with their microenvironment as well as on the inducing factors and elements in this environment. Strategies to modulate the immune system in the TME of BC that are aimed at reversing the suppressive networks within it and eradicating residual CSCs are, thus, essential for improving the current therapeutic efficacy of BC. This review focuses on the development of immunoresistance in BCs and discusses the strategies that can modulate the immune system and target breast CSCs directly to treat BC including immunotherapy with immune checkpoint blockades.

Construction and Validation of a Nomogram for Predicting Acute Kidney Injury After Hip Fracture Surgery.

Background: Acute kidney injury (AKI), characterized by sudden impairment of kidney function, is an uncommon complication following hip fracture surgery that is associated with increased morbidity and mortality. We constructed a nomogram to stratify patients according to risk of AKI after hip fracture surgery to guide clinicians in the implementation of timely interventions. Methods: Patients who received hip fracture surgery from January 2015 to December 2021 were retrospectively identified and divided into a training set (n=448, surgery from January 2015 to December 2019) and a validation set (n=200, surgery from January 2020 to December 2021). Univariate and multivariate logistic regression were used to identify risk factors for AKI after surgery in the training set. A nomogram was constructed based the risk factors for AKI, and was evaluated by receiver operating characteristic (ROC) analysis, calibration curves, and decision curve analysis (DCA). Results: The mean age was 82.0±6.22 years-old and the prevalence of post-surgical AKI was 13.3%. Age, American Society of Anesthesiologists (ASA) score, the preexistence of chronic kidney disease (CKD), cemented surgery and the decrease of hemoglobin on the first day after surgery were identified as independent risk factors of AKI after hip fracture surgery, and a predictive nomogram was established based on the multivariable model. The predictive nomogram had good discrimination ability (training set: AUC: 0.784, 95% CI: 0.720-0.848; validation set: AUC: 0.804, 95% CI: 0.704-0.903), and showed good validation ability and clinical usefulness based on a calibration plot and decision curve analysis. Conclusion: A nomogram that incorporated five risk factors including age, ASA score, preexisting CKD, cemented surgery and the decrease of hemoglobin on the first day after surgery had good predictive performance and discrimination. Use of our results for early stratification and intervention has the potential to improve the outcomes of patients receiving hip fracture surgery. Future large, multicenter cohorts are needed to verify the model's performance.

Obese elderly patients with hip fractures may have better survival outcomes after surgery.

BACKGROUND: In recent years, there has been an increasing amount of research on the "obesity paradox". So our primary objective was to explore whether this phenomenon exists in our study, and secondary objective was to determine the effect of body mass index (BMI) on major complications, and the incidence of acute kidney injury (AKI) after hip fracture surgery after controlling for confounding factors. METHODS: We included patients over 70 years old with hip fracture who were admitted to the Department of Orthopedics, Peking University First Hospital between 2015 and 2021. Patients were classified as underweight (UW, < 18.5 kg/m2), normal weight (NW, 18.5-24.9 kg/m2), overweight (OW, 25.0-29.9 kg/m2) and obese (OB, ≥ 30.0 kg/m2). We analyzed demographic characteristics, operation information and postoperative outcomes. Using multivariate regression with normal-weight patients as the reference, we determined the odds of 1-year mortality, major complications, and AKI by BMI category. RESULTS: A total of 644 patients were included. Nine percent of patients died after 1 year, 18% had major postoperative complications, and 12% had AKI. There was a U-shaped relationship between BMI and the rates of major complications or AKI. However, there was a linear decreasing relationship between 1-year mortality and BMI. After controlling for confounding factors, multivariate regression analysis showed that the risk of 1-year mortality after surgery was 2.24 times higher in underweight patients than in normal-weight patients (P < 0.05, OR: 2.24, 95% CI 1.14-4.42). Compared with normal-weight patients, underweight patients had a 2.07 times increased risk of major complications (P < 0.05, OR 2.07, 95% CI 1.21-3.55), and the risk of major complications in obese patients was 2.57 times higher than that in normal-weight patients (P < 0.05, OR 2.57, 95% CI 1.09-6.09). Compared with normal-weight, underweight patients had a 2.18 times increased risk of AKI (P < 0.05, OR 2.18, 95% CI 1.17-4.05). CONCLUSIONS: The 1-year mortality risk of patients with higher BMI was significantly reduced. Besides, compared with normal-weight patients, underweight patients and obese patients have a higher risk of major complications; low-weight and obese patients are at higher risk for AKI.

Decrease in Secondhand Smoke Exposure in Work and Public Places among Adults in the Philippines: An Analysis of the Global Adult Tobacco Survey, 2009 and 2015.

The implementation of several tobacco control policies in the Philippines may have contributed to a decrease in secondhand smoke (SHS) exposure. We examined changes in SHS exposure at work and in public places between 2009 and 2015 among adults aged ≥15 years and interpreted these results within the tobacco policy landscape in the Philippines. We analyzed the Philippines Global Adult Tobacco Survey 2009 and 2015 data. We examined marginal effects in logistic regression to get the adjusted prevalence of SHS exposure at five work and public places, controlling for selected characteristics. We calculated adjusted prevalence ratios and adjusted prevalence differences between 2009 and 2015. Adjusted prevalence of SHS exposure decreased from 2009 to 2015 by 19% (5.7 percentage points) at work, 45% (11.2 percentage points) in government buildings, 48% (3.2 percentage points) in healthcare facilities, 29% (8.2 percentage points) in restaurants, and 33% (19.9 percentage points) on public transportation. Although the prevalence of SHS exposure at work and in public places decreased significantly between 2009 and 2015, a substantial proportion of adults remain exposed to SHS. This study highlights the importance of continued implementation, enforcement, monitoring, and evaluation of tobacco control and prevention measures in the Philippines.

Updated information regarding acute severe hepatitis of unknown origin in children: Viewpoints of and insights from pediatricians.

Recently, the morbidity of acute severe hepatitis of unknown origin in children (SHIC) has tended to decrease, but this condition should not be ignored because of its uncertain but severe nature. The current study briefly summarizes updated information regarding the epidemiological, clinical, and etiological aspects of SHIC based on the newest information available. Opinions from pediatricians are also presented. In light of the status quo of SHIC and COVID-19 globally, several suggestions are proposed to improve future studies, which could help to further explore the underlying mechanisms of SHIC in the context of COVID-19.

Activatable Self-Dissociation of Watson-Crick Structures with Fluorescent Nucleotides for Sensing Multiple Human Glycosylases at Single-Cell Level.

Nucleobase oxidation and alkylation can destroy Watson-Crick base-pairing to challenge the genomic integrity. Human 8-oxoguanine glycosylase 1 (hOGG1) and alkyladenine glycosylase (hAAG) are evolved to counter these two cytotoxic lesions through base-excision repair, and their deregulations are implicated with multifactorial diseases and cancers. Herein, we demonstrate activatable self-dissociation of Watson-Crick structures with fluorescent nucleotides for sensing multiple human glycosylases at single-cell level. The presence of hOGG1 and hAAG catalyzes 8-oxoG and deoxyinosine removal in functional probe 1 to release two trigger probes (1 and 2). Then, trigger probes hybridize with functional probe 2 to activate the autocatalytic degradation of functional probes 2 (Cycle I) and 3 (Cycle II), replicating abundant trigger probes (1-4) and releasing two fluorophores (2-aminopurine (2-AP) and pyrrolo-dC (P-dC)). New trigger probes (1, 2) and (3, 4), in turn, hybridize with free functional probes 2 and 3, repeating Cycles I and II turnovers. Through multicycle self-dissociation of Watson-Crick structures, 2-AP and P-dC are exponentially accumulated for the simultaneous quantification of hOGG1 and hAAG. This nanodevice exhibits high sensitivity with a detection limit of 2.9 × 10-3 U/mL for hOOG1 and 1.5 × 10-3 U/mL for hAAG, and it can measure enzymatic kinetics, identify potential inhibitors, discriminate glycosylases between cancer and normal cell lines, and even quantify glycosylase activities in a single HeLa cell. Moreover, this assay may be rapidly and isothermally performed in one tube with only one tool enzyme in a quencher-free manner, promising a simple and powerful platform for multiple human glycosylase detection.

C-reactive protein (CRP)/albumin-to-globulin ratio (AGR) is a valuable test for diagnosing periprosthetic joint infection: a single-center retrospective study.

BACKGROUND: The diagnosis of periprosthetic joint infection (PJI) is challenging for clinicians, and the commonly used methods are too complicated and expensive for many clinical practices. The neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the platelet-to-mean-platelet-volume ratio (PVR), globulin (GLB), the albumin-to-globulin ratio (AGR), and the C-reactive protein (CRP)/AGR ratio are simple biomarkers for infection and can be easily determined from routine blood tests. Due to their low cost and ready availability in clinical practice, many clinicians have considered the diagnostic value of these biomarkers for PJI. The aim of our study is to determine the value of NLR, PLR, PVR, GLB, AGR, and CRP/AGR for the diagnosis of PJI. MATERIALS AND METHODS: One hundred sixty-four patients who received revision surgery after total knee or total hip replacements were enrolled, 47 in a PJI group and 117 in an aseptic failure group. Receiver operating characteristic (ROC) analysis was used to evaluate the performance of NLR, PLR, PVR, GLB, AGR, and CRP/AGR for the diagnosis of PJI, and their performance levels were then compared with those of CRP and the erythrocyte sedimentation rate (ESR). RESULTS: The levels of all tested biomarkers were significantly higher in patients with PJI (all P < 0.05). ROC analysis showed that CRP/AGR performed best in diagnosing PJI, with an area under curve (AUC) value of 0.902, and the AUCs of NLR (0.740), PLR (0.721), PVR (0.668), GLB (0.719), and AGR (0.767) were all lower than those for CRP (0.896) and ESR (0.829). CONCLUSION: CRP/AGR was a valuable test for diagnosing PJI, but other novel biomarkers had only limited diagnostic value. LEVEL OF EVIDENCE: Level III.

Simultaneous Detection of Pathogens and Tumors in Patients With Suspected Infections by Next-Generation Sequencing.

Background: Differential diagnosis of patients with suspected infections is particularly difficult, but necessary for prompt diagnosis and rational use of antibiotics. A substantial proportion of these patients have non-infectious diseases that include malignant tumors. This study aimed to explore the clinical value of metagenomic next-generation sequencing (mNGS) for tumor detection in patients with suspected infections. Methods: A multicenter, prospective case study involving patients diagnosed with suspected infections was conducted in four hospitals in Shanghai, China between July 2019 and January 2020. Based upon mNGS technologies and chromosomal copy number variation (CNV) analysis on abundant human genome, a new procedure named Onco-mNGS was established to simultaneously detect pathogens and malignant tumors in all of the collected samples from patients. Results: Of 140 patients screened by Onco-mNGS testing, 115 patients were diagnosed with infections; 17 had obvious abnormal CNV signals indicating malignant tumors that were confirmed clinically. The positive percent agreement and negative percent agreement of mNGS testing compared to clinical diagnosis was 53.0% (61/115) and 60% (15/25), vs. 20.9% (24/115) and 96.0% (24/25), respectively, for conventional microbiological testing (both P <0.01). Klebsiella pneumoniae (14.8%, 9/61) was the most common pathogen detected by mNGS, followed by Escherichia coli (11.5%, 7/61) and viruses (11.5%, 7/61). The chromosomal abnormalities of the 17 cases included genome-wide variations and local variations of a certain chromosome. Five of 17 patients had a final confirmed with malignant tumors, including three lung adenocarcinomas and two hematological tumors; one patient was highly suspected to have lymphoma; and 11 patients had a prior history of malignant tumor. Conclusion: This preliminary study demonstrates the feasibility and clinical value of using Onco-mNGS to simultaneously search for potential pathogens and malignant tumors in patients with suspected infections.