Sex differences in the global burden of multidrug- resistant tuberculosis without extensive drug resistance in the general population and people living with HIV/AIDS, 1990-2019.

OBJECTIVE: Currently, human immunodeficiency virus (HIV) and multi-drug resistant tuberculosis (MDR-TB) without extensive drug resistance (XDR) are significant challenges in terms of the global burden of disease. This study aimed to evaluate the trends of the global burden of MDR-TB without XDR and HIV/AIDS-MDR-TB without XDR, focusing on differences in socioeconomic status and sex for 204 countries and territories across periods from 1990 to 2019. MATERIALS AND METHODS: Data from the Global Burden of Disease (GBD) 2019 study were obtained to construct a separate index measuring the burden of MDR-TB without XDR and HIV/AIDS-MDR-TB without XDR. Incidence, prevalence, mortality, and disability-adjusted life years (DALYs) were calculated for each case and group. A population-attributable fraction approach was used to assess mortality and incidence of HIV/AIDS and MDR-TB coinfection. 95% uncertainty intervals (UIs) were presented for all measures. RESULTS: Our global estimates suggest that there were approximately 450,000 (95% UI 247,000-785,000) incident cases of MDR-TB without XDR and 109,000 (43,000-210,000) deaths caused by MDR-TB without XDR among individuals who were HIV-negative in 2019. For HIV-positive individuals, the corresponding figures were approximately 47,000 (33,000-67,000) incident cases of MDR-TB and 19,000 (8,000-36,000) deaths due to MDR-TB in the same year. In 2019, higher numbers of incident cases and deaths were observed in males compared to females among individuals who were HIV-negative. Conversely, for HIV-positive individuals, females had higher numbers of incident cases and deaths compared to males. Specifically, the estimated numbers for incident cases were 23,000 (15,000-33,000) for females and 24,000 (17,000-35,000) for males, while the estimated numbers for deaths were 9,600 (4,000-17,900) for females and 9,800 (4,100-18,500) for males. Male-to-female ratios have remained above 1.0 from 1990 to 2019 in both incident cases and number of deaths for HIV-negative individuals. However, for HIV and MDR-TB coinfection, both ratios were below 1.0 in most of the time series. CONCLUSIONS: Males had more cases and deaths due to MDR-TB without XDR than females in HIV-negative patients, while females faced a higher incidence and mortality in HIV/AIDS-MDR-TB without XDR. Interventions are needed to deal with such factors, which increase the burden of coinfection among females across the world.

National prevalence and socioeconomic factors associated with the acceptance of COVID-19 vaccines in South Korea: a large-scale representative study in 2021.

OBJECTIVE: Among the global efforts toward preventing the COVID-19 pandemic, vaccines are a pivotal factor in ending the pandemic. Thus, through a large-scale population-based study, we investigated the individual-, social-, and family-associated factors affecting the acceptance of COVID-19 vaccines in South Korea. PATIENTS AND METHODS: Data were obtained from a nationwide representative study (Korea Community Health) conducted in 2021. To determine the individual-, social-, and family-associated variables for COVID-19 vaccination acceptance, we investigated data from 225,319 individuals. RESULTS: In the total sample (n=225,319), 184,529 COVID-19-vaccinated people and 40,790 non-vaccinated people were evaluated. The factors related to the acceptance of COVID-19 vaccination were significantly associated with the demographic factors, namely, older age group, female sex, and a history of influenza vaccination, as well as medical conditions such as diabetes, hypertension, and depression. Socioeconomic conditions influencing the acceptance of COVID-19 vaccination were significantly associated with low-income families and blue-collar workers. Health-related risk factors were high in the obese group. However, a noteworthy negative association was found between the acceptance of vaccination and smoking habits and alcohol consumption. Conversely, a positive association was observed between academic level and vaccination acceptance. CONCLUSIONS: Our findings suggest that old age, female sex, a history of influenza vaccination, medical conditions, such as diabetes, hypertension, and depression, low-income families, blue-collar workers, and health-related risk factors, such as obesity, were associated with the acceptance of COVID-19 vaccination. Additionally, a high academic level, absence of smoking habits, and non-current alcohol use were positively associated with vaccine acceptance.

National prevalence and determinants of COVID-19 vaccine hesitancy during the initial phase pandemic.

OBJECTIVE: Although previous studies have explored the causes of COVID-19 vaccine hesitancy during the pandemic, there is a lack of generality and reproducibility in these studies. Therefore, we aimed to comprehensively identify the determinants of COVID-19 vaccine hesitancy through a representative nationwide cross-sectional study conducted in South Korea. SUBJECTS AND METHODS: We used a nationwide, representative, and large-scale dataset from the 2021 Community Health Survey. By analyzing 193,495 participants, we investigated the nationwide incidence of COVID-19 vaccine hesitancy and the various causes thereof. RESULTS: The national prevalence of COVID-19 vaccine hesitancy was 5.7% (95% CI, 5.5-5.8). COVID-19 vaccine hesitancy was associated with an increased incidence of the following factors: (1) demographic factors including early-middle adulthood [vs. late; odds ratio (OR), 1.51; 95% CI, 1.38-1.65] and male sex (vs. female sex; OR, 1.08; 95% CI, 1.01-1.14); (2) physically healthy subjects; (3) lower socio-economic status (vs. high household income; OR, 1.28; 95% CI, 1.19-1.38); (4) having mental illness (vs. normal mental status; OR, 1.25; 95% CI, 1.13-1.38); and (5) unhealthy habits such as current smoking (vs. non-smoking; OR, 1.22; 95% CI, 1.13-1.31); and insufficient physical activity (vs. sufficient; OR, 1.08; 95% CI, 1.01-1.17). Common reasons for vaccine hesitancy were concerns about side effects (41.34%), health problems (24.60%), and inability to select the type of vaccine (14.13%). CONCLUSIONS: This representative large-scale nationwide study conducted in South Korea investigated the nationwide prevalence and determinants of vaccine hesitancy. Our results provide useful public health information, especially on novel aspects of vaccination strategies, for policymakers to improve the acceptance of COVID-19 vaccines.

Ethnic and sex differences in the distributions of body mass index and waist circumference among adults: a binationally representative study in South Korea and the United States.

OBJECTIVE: The ethnic and sex differences in the distributions of body mass index (BMI) and waist circumference (WC) among adults are largely unknown. Therefore, we aimed to investigate the percentiles of BMI and WC in groups divided according to age, sex, and ethnicity. PATIENTS AND METHODS: We conducted a population-based binational study of adults aged ≥20 years based on data from two sources: US National Health and Nutrition Examination Survey (2015 to 2020) and Korea National Health and Nutrition Examination Survey (2016 to 2019). RESULTS: Weight, height, and WC were measured in 13,144 American adults and 30,191 Korean adults. Overall, BMI increased at younger ages and decreased at older ages, which indicates a reversed U-shaped relationship, and differed in terms of age, sex, and ethnicity. Women in the other Hispanic, non-Hispanic white, non-Hispanic black, and "other ethnic groups" showed a common BMI peak at ages 50-54 years. The patterns of WC distribution were similar to those of BMI distribution. CONCLUSIONS: In this binational representative study, we found varied distributions of ethnic and sex differences in BMI and WC. Considering the differences in these distributions may help improve individual and personalized treatment strategies.

Temporal characterization of a two-color laser field using tunneling ionization.

The superposition of a fundamental laser pulse and its second harmonic can form an asymmetric laser field that is useful in many applications. The temporal characterization of the two-color laser field becomes necessary. However, the temporal characterization of the two-color laser pulse is a challenging task due to its broad bandwidth and a spectral gap between the two frequency components. Here we demonstrate the temporal characterization of the two-color laser field using multiple ionization yield measurements near the laser focus. This new approach enables the complete temporal characterization of the two-color laser field, including the relative phase between the two frequency components.

Stachydrine alleviates lipid-induced skeletal muscle insulin resistance via AMPK/HO-1-mediated suppression of inflammation and endoplasmic reticulum stress.

OBJECTIVE: Insulin resistance develops due to skeletal muscle inflammation and endoplasmic reticulum (ER) stress. Stachydrine (STA), extracted from Leonurus heterophyllus, has been shown to suppress proliferation and induce apoptosis in breast cancer cells and exert anti-inflammatory properties in the brain, heart, and liver. However, the roles of STA in insulin signaling in skeletal muscle remain unclear. Herein, we examined the impacts of STA on insulin signaling in skeletal muscle under hyperlipidemic conditions and its related molecular mechanisms. METHODS: Various protein expression levels were determined by Western blotting. Levels of mouse serum cytokines were measured by ELISA. RESULTS: We found that STA-ameliorated inflammation and ER stress, leading to attenuation of insulin resistance in palmitate-treated C2C12 myocytes. STA dose-dependently enhanced AMPK phosphorylation and HO-1 expression. Administration of STA attenuated not only insulin resistance but also inflammation and ER stress in the skeletal muscle of high-fat diet (HFD)-fed mice. Additionally, STA-ameliorated glucose tolerance and insulin sensitivity, as well as serum TNFα and MCP-1, in mice fed a HFD. Small interfering (si) RNA-associated suppression of AMPK or HO-1 expression abolished the effects of STA in C2C12 myocytes. CONCLUSIONS: These results suggest that STA activates AMPK/HO-1 signaling, resulting in reduced inflammation and ER stress, thereby improving skeletal muscle insulin resistance. Using STA as a natural ingredient, this research successfully treated insulin resistance and type 2 diabetes.

Mindfulness-Based Intervention for Caregivers of Frail Older Chinese Adults: A Study Protocol.

Studies have consistently showed that informal caregivers have worse health, more medical consultations, anxiety and depression, and lower quality of life than those who do not provide such care. Positive outcomes of psychoeducation interventions have been found, but many of them are relatively long in duration, making them less cost-effective in implementation. The proposed study is a multi-site, three-arm randomized controlled trial of a mindfulness-based intervention for Chinese family caregivers. Effects of the intervention will be compared with those of an evidence-based psychoeducation program and treatment-as-usual. Two hundred forty cross-generational caregivers of frail older adults with moderate to severe levels of frailty will be recruited and randomly assigned to mindfulness-based intervention, psychoeducation, and treatment-as-usual experimental conditions. Program effectiveness will be analyzed on measures of caregiver burden, depression, anxiety, positive caregiving experience, spirituality, family conflict, and the biomarker of heart rate variability. Measures on coping styles, experiential avoidance, and self-efficacy will be explored to see if they mediate the changes to participant improvements in outcomes. Six-month follow-up will be included to investigate the maintenance effects. This study will provide evidence on mindfulness-based interventions on caregivers of frail older adults and expand the existing models of intergenerational caregiving in Chinese culture.

Adolescence alcohol exposure impairs fear extinction and alters medial prefrontal cortex plasticity.

After experiencing a traumatic event people often turn to alcohol to cope with symptoms. In those with post-traumatic stress disorder (PTSD) and a co-occurring alcohol use disorder (AUD), PTSD symptoms can worsen, suggesting that alcohol changes how traumatic memory is expressed. The objective of this series of experiments is to identify how alcohol drinking (EtOH), following cued fear conditioning and extinction, impacts fear expression in mice. Molecular (activity-regulated cytoskeleton-associated protein, Arc/arg3.1) and structural (dendrite and spine morphometry) markers of neuronal plasticity were measured following remote extinction retrieval. Mouse age (adolescent and adult) and sex were included as interacting variables in a full factorial design. Females drank more EtOH than males and adolescents drank more EtOH than adults. Adolescent females escalated EtOH intake across drinking days. Adolescent drinkers exhibited more conditioned freezing during extinction retrieval, an effect that persisted for at least 20 days. Heightened cued freezing in the adolescent group was associated with greater Arc/arg3.1 expression in layer (L) 2/3 prelimbic (PL) cortex, greater spine density, and reduced basal dendrite complexity. In adults, drinking was associated with reduced L2/3 infralimbic (IL) Arc expression but no behavioral differences. Few sex interactions were uncovered throughout. Overall, these data identify prolonged age-related differences in alcohol-induced fear extinction impairment and medial prefrontal cortex neuroadaptations.

Round window membrane rupture following blunt force trauma.

Round window rupture following barotrauma such as diving and air travel is well documented. However, we describe a case of round window rupture following a slap to the ear, which has not been described previously. A 12-year-old boy was slapped by his teacher in rural Nepal over his left ear and immediately noted hearing loss. There was no dizziness or tinnitus. He presented to our unit 21 days after the trauma and examination showed a perforation of the tympanic membrane in the anterior inferior quadrant with an otherwise normal ear examination and no nystagmus seen. Audiogram showed a left profound hearing loss, which was supported by auditory brainstem response test. Exploratory tympanotomy showed active perilymph leakage from the round window niche as demonstrated in the video attached. The round window was packed with cartilage and fascia to address the perilymph leakage. The patient was discharged the following day without any complications. This is an unusual cause for round window membrane rupture where the patient presented with hearing loss as his only symptom. Tympanotomy is recommended for patients with hearing loss following trauma with normal computed tomography imaging to exclude perilymph leak secondary to inner ear barotrauma.

Prognosticating patients with necrotising otitis externa based on response to treatment.

INTRODUCTION: Necrotising otitis externa (NOE) is a severe infection of the temporal bone. The traditional severity based staging system does not fully prognosticate all patients with NOE. We hypothesise that a patient response staging system would more accurately capture the disease process and guide prognosis. METHODS: We carried out a retrospective notes review of patients diagnosed with NOE from January 2017 to December 2018 in a regional tertiary referral centre. Patient outcomes from our proposed patient response staging system were compared to a modified previously published severity based Gleeson staging system with patients requiring prolonged treatment classified as having a poor outcome. RESULTS: A total of 34 patients were treated for NOE. The majority were male (n=24) and had diabetes (n=25). Patients with the most severe Gleeson staging did not have the worst outcome. Daily delay in resolution of otorrhoea was associated with an increased need for more than six weeks of treatment. Rapid responders are patients who had resolution of otalgia, otorrhoea and C-reactive protein normalisation within 14 days, and all were cured following standard 6 weeks of treatment. CONCLUSIONS: The Gleeson staging system was valuable in assessing the extent of disease and all early Gleeson staged patients had good outcomes. However, patients with higher severity staging on the Gleeson system did not necessarily require prolonged treatment. There is a role for a joint approach in staging patients based on both modified Gleeson and treatment response, which would subsequently guide prognosis, duration of treatment and early diagnosis of potential fungal NOE.

Suspected Metallic Embolization Distal to Coiled Intracranial Aneurysms Detectable by Susceptibility-Weighted MR Imaging.

BACKGROUND AND PURPOSE: After endovascular coiling of intracranial aneurysms, round dark parenchymal lesions believed to be particulate metal are sometimes encountered in MR imaging studies of the brain. We used SWI to assess the frequency of such occurrences, in addition to exploring likely causes and clinical implications. MATERIALS AND METHODS: We reviewed 700 MR imaging studies performed between September 2018 and March 2019 at our institution as follow-up monitoring of coiled intracranial aneurysms. Any sizeable (>5 mm) rounded dark-signal lesions encountered were presumed to be metallic. The magnitudes and locations of such lesions were recorded. In patients with these lesions, pertinent procedural documentation was screened for devices used, including coils, microcatheters, microguidewires, and stents. Medical records were also examined to determine whether any related symptoms ensued. RESULTS: Twenty patients (2.8%) exhibited a total of 25 lesions on SWI. Diameters ranged from 5 to 11 mm (median, 8 mm). All except 2 lesions were located in brain regions downstream from aneurysms, but all lesions occupied vascular territories of vessels used to place guiding catheters. Other than the Synchro 14, which was routinely deployed, no device was regularly used in patients with SWI-detectable lesions; and none of the affected patients developed focal neurologic symptoms as a consequence. CONCLUSIONS: Although the origins remain unclear, distal embolization of particulate metal distal to coiled cerebral aneurysms is occasionally observed on follow-up MR imaging studies. Such lesions, however, seem to have no apparent clinical impact.

Detection of the mesenchymal-to-epithelial transition of invasive non-small cell lung cancer cells by their membrane undulation spectra.

A cancer cell changes its state from being epithelial- to mesenchymal-like in a dynamic manner during tumor progression. For example, it is well known that mesenchymal-to-epithelial transition (MET) is essential for cancer cells to regain the capability of seeding on and then invading secondary/tertiary regions. However, there is no fast yet reliable method for detecting this transition. Here, we showed that membrane undulation of invasive cancer cells could be used as a novel marker for MET detection, both in invasive model cell lines and repopulated circulating tumor cells (rCTCs) from non-small cell lung cancer (NSCLC) patients. Specifically, using atomic force microscopy (AFM), it was found that the surface oscillation spectra of different cancer cells, after undergoing MET, all exhibited two distinct peaks from 0.001 to 0.007 Hz that are absent in the spectra before MET. In addition, by adopting the long short-term memory (LSTM) based recurrent neural network learning algorithm, we showed that the positions of recorded membrane undulation peaks can be used to predict the occurrence of MET in invasive NSCLC cells with high accuracy (>90% for model cell lines and >80% for rCTCs when benchmarking against the conventional bio-marker vimentin). These findings demonstrate the potential of our approach in achieving rapid MET detection with a much reduced cell sample size as well as quantifying changes in the mesenchymal level of tumor cells.

Role of TGF-ß1 and C-Kit Mutations in the Development of Hepatocellular Carcinoma in Hepatitis C Virus-Infected Patients: in vitro Study.

Transforming growth factor beta (TGF-ß) acts as a tumor-suppressing cytokine in healthy tissues and non-malignant tumors. Yet, in malignancy, TGF-ß can exert the opposite effects that can promote proliferation of cancer cells. C-Kit plays a prominent role in stem cell activation and liver regeneration after injury. However, little is known about the cross-talk between TGF-ß and C-Kit and its role in the progression of hepatocellular carcinoma (HCC). Here, we studied the effect of increasing doses of TGF-ß1 on CD44+CD90+ liver stem cells (LSCs) and C-Kit gene expression in malignant and adjacent non-malignant liver tissues excised from 32 HCC patients. The percentage of LSCs in malignant tumors was two times higher compared to their counterparts from the non-malignant tissues. When treated with increasing doses of TGF-ß1, proliferation of both malignant and non-malignant LSCs was progressively suppressed, but low TGF-ß1 dose failed to suppress the growth of malignant LSCs. Moreover, C-Kit exons 9 and 11 were expressed in malignant LSCs, but not in their non-malignant counterparts. Analysis of C-Kit detected mutations in exon 9 (but not in exon 11) in some malignant liver cells resulting in the changes in the amino acid sequence and dysregulation of protein structure and function. Interestingly, in malignant liver cells, mutations in exon 9 were associated with high-viremia hepatitis C virus (HCV), and expression of this exon was not suppressed by the TGF-ß1 treatment at all doses. To our knowledge, this is the first report that mutations in the C-Kit gene in HCC patients are associated with high- viremia HCV. Our study emphasizes the need for investigation of the TGF-ß1 level and C-Kit mutations in patients with chronic HCV for HCC prevention and better therapy management.

An electro-osmotic microfluidic system to characterize cancer cell migration under confinement.

We have developed a novel electro-osmotic microfluidic system to apply precisely controlled osmolarity gradients to cancer cells in micro-channels. We observed that albeit adhesion is not required for cells to migrate in such a confined microenvironment, the migrating velocity of cells is strongly influenced by the interactions between the cells and the channel wall, with a stronger adhesion leading to diminished cell motility. Furthermore, through examining more than 20 different types of cancer cells, we found a linear positive correlation between the protein concentration of the aquaporin-4 (AQP4) and the cell migrating speed. Knockdown of AQP4 in invasive re-populated cancer stem cells reduced their migration capability down to the level that is comparable to their parental cancer cells. Interestingly, these observations can all be quantitatively explained by the osmotic engine model where the cell movement is assumed to be driven by cross-membrane ion/water transport, while adhesion acts as a frictional resistance against the cell motility. By providing versatile and controllable features in regulating and characterizing the migration capability of cells, our system may serve as a useful tool in quantifying how cell motility is influenced by different physical and biochemical factors, as well as elucidating the mechanisms behind, in the future.

Prone positioning before extracorporeal membrane oxygenation for severe acute respiratory distress syndrome: A retrospective multicenter study.

OBJECTIVE: To evaluate the clinical outcomes of patients with severe acute respiratory distress syndrome (ARDS) subjected to prone positioning before extracorporeal membrane oxygenation (ECMO). DESIGN: A retrospective analysis of a multicenter cohort was carried out. SETTING: Patients admitted to the Intensive Care Units of 11 hospitals in Korea. PATIENTS: Patients were divided into those who underwent prone positioning before ECMO (n=28) and those who did not (n=34). INTERVENTIONS: None. VARIABLES OF INTEREST: Thirty-day mortality, ECMO weaning failure rate, mechanical ventilation weaning success rate, mechanical ventilation-free days at day 60. RESULTS: The prone group had lower median peak inspiratory pressure and lower median dynamic driving pressure before ECMO. Thirty-day mortality was 21% in the prone group and 41% in the non-prone group (p=0.098). The prone group also showed a lower ECMO weaning failure rate, and a higher mechanical ventilation weaning success rate and more mechanical ventilation-free days at day 60. In the non-prone group, median dynamic compliance marginally decreased shortly after ECMO, but no significant change was observed in the prone group. CONCLUSIONS: Prone positioning before ECMO was not associated to increased mortality and tended to exert a protective effect.

First Report of the Korean Lung Transplantation Registry.

BACKGROUND: The Korean Organ Transplantation Registry (KOTRY) began to register lung transplants in 2015. This is an initial report on the status of patients receiving lung transplants over the past 2 years. METHODS: We analyzed a total of 69 patients who received lung transplants in 2015 and 2016 and who registered with the KOTRY. RESULTS: The 69 patients were treated in 5 institutions. The average (SD) donor age was 39.2 (12.6) years; there were 40 male patients. The average (SD) recipient age was 55.7 (10.0) years, and the number of male recipients was 46. A total of 66 patients underwent bilateral lung transplantation, 3 underwent single-lung transplantation, and 1 underwent simultaneous heart-lung transplantation. The most frequent indication for lung transplantation was idiopathic pulmonary fibrosis (35 patients), followed by connective tissue disease-related interstitial lung disease (9) and acute respiratory failure (8). Prior to transplantation, 23 patients required ventilator care, and 12 required extracorporeal membrane oxygenation while on the waiting list. Episodes of acute rejection during follow-up were reported in 4, 2, 1, and 1 patients at 3, 6, 9, and 12 months, respectively. Infections requiring hospitalization were reported in 27, 10, 4, and 3 patients at 3, 6, 9, and 12 months, respectively. CONCLUSION: The establishment of KOTRY renders it possible to collect nationwide data on lung transplantation, improving research on the topic and clarifying clinical feasibility.

Sporicidal activities and mechanism of surfactant components against Clostridium sporogenes spores.

The sporicidal activities of seven kinds of antimicrobial agent were investigated in order to screen for novel inactivation agents to apply to Clostridium sporogenes spores. Antimicrobial agents based on surfactant components, as poly-l-lysine, thiamine dilaurylsulfate, and torilin, were more effective than other agents. The degree of spore reduction with 1-2% surfactant components was 1.5-2.5 log CFU/mL. The HLB value (hydrophile-lipophile balance) related to denature protein of spores coat on surfactants with sporicidal activity was ranged from 6 to 16. Average HLB value and spore killing effect was inversely correlated. The proteins on spore structures seemed to be disorganized due to binding between polar groups of coats and hydrophilic and hydrophobic groups of surfactant components, resulting in killing of spores. The components that were effective to inactivate C. sporogenes spores had a chemical structure containing CH3, OH, COOH, sulfate groups, and a double bond. Furthermore, hydrophobic surfactants were more effective than hydrophilic surfactants in inactivating spores. This was likely due to the type of hydrophobic surfactant and to the involvement of hydrophobic interactions on coat of spores.