A lactate-induced response to hypoxia.

Organisms must be able to respond to low oxygen in a number of homeostatic and pathological contexts. Regulation of hypoxic responses via the hypoxia-inducible factor (HIF) is well established, but evidence indicates that other, HIF-independent mechanisms are also involved. Here, we report a hypoxic response that depends on the accumulation of lactate, a metabolite whose production increases in hypoxic conditions. We find that the NDRG3 protein is degraded in a PHD2/VHL-dependent manner in normoxia but is protected from destruction by binding to lactate that accumulates under hypoxia. The stabilized NDRG3 protein binds c-Raf to mediate hypoxia-induced activation of Raf-ERK pathway, promoting angiogenesis and cell growth. Inhibiting cellular lactate production abolishes the NDRG3-mediated hypoxia responses. Our study, therefore, elucidates the molecular basis for lactate-induced hypoxia signaling, which can be exploited for the development of therapies targeting hypoxia-induced diseases.

Modifiable lifestyle factors and lifetime risk of atrial fibrillation: longitudinal data from the Korea NHIS-HealS and UK Biobank cohorts.

BACKGROUND: The reason for higher incidence of atrial fibrillation (AF) in Europe compared with East Asia is unclear. We aimed to investigate the association between modifiable lifestyle factors and lifetime risk of AF in Europe and East Asia, along with race/ethnic similarities and disparities. METHODS: 1:1 propensity score matched pairs of 242,763 East Asians and 242,763 White Europeans without AF were analyzed. Modifiable lifestyle factors considered were blood pressure, body mass index, cigarette smoking, diabetes, alcohol consumption, and physical activity, categorized as non-adverse or adverse levels. Lifetime risk of AF was estimated from the index age of 45 years to the attained age of 85 years, accounting for the competing risk of death. RESULTS: The overall lifetime risk of AF was higher in White Europeans than East Asians (20.9% vs 15.4%, p < 0.001). The lifetime risk of AF was similar between the two races in individuals with non-adverse lifestyle factor profiles (13.4% vs 12.9%, p = 0.575), whereas it was higher in White Europeans with adverse lifestyle factor profiles (22.1% vs 15.8%, p < 0.001). The difference in the lifetime risk of AF between the two races increased as the burden of adverse lifestyle factors worsened (1 adverse lifestyle factor; 4.3% to ≥ 3 adverse lifestyle factors; 11.2%). Compared with East Asians, the relative risk of AF in White Europeans was 23% and 62% higher for one (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.16-1.29) and ≥ 3 adverse lifestyle factors (HR 1.62, 95% CI 1.51-1.75), respectively. CONCLUSIONS: The overall higher lifetime risk of AF in White Europeans compared with East Asians might be attributable to adverse lifestyle factors. Adherence to healthy lifestyle factors was associated with the lifetime risk of AF of about 1 in 8 regardless of race/ethnicity.

Case report: atypical presentation of mpox with massive hematochezia and prolonged viral shedding despite tecovirimat treatment.

BACKGROUND: The outbreak of mpox that occurred between 2022 and 2023 is primarily being transmitted through sexual contact. As of now, there is no consensus on the recommended duration of isolation to prevent sexual transmission of the virus. Moreover, this particular mpox outbreak has presented with distinct complications in comparison to previous occurrences. In this report, we present a case involving severe rectal bleeding from an ulcer in a mpox patient with a history of engaging in receptive sexual contact. CASE PRESENTATION: A 30-year-old Korean man presented at the hospital with complaints of fever, multiple skin lesions, and anal pain. Monkeypox virus polymerase chain reaction (PCR) results were positive for skin lesions on the penis and wrist. The patient received a 12-day course of tecovirimat due to anal symptoms and perianal skin lesions. Following isolation for 12 days and after all skin scabs had naturally fallen off, with no new skin lesions emerging for a consecutive 48 hours-conforming to the criteria of the Korean Disease Control and Prevention Agency-the patient was discharged. However, 1 day after discharge, the patient returned to the hospital due to hematochezia. His hemoglobin level had significantly dropped from 14.0 g/dL to 8.2 g/dL. Sigmoidoscopy unveiled a sizable rectal ulceration with exposed blood vessels, prompting the application of hemostasis through metal clipping. Subsequent monkeypox virus real-time PCR conducted on rectal tissue and swabs yielded positive results (with cycle threshold values of 28.48 and 31.23, respectively). An abdominal CT scan exposed a perirectal abscess, for which ampicillin-sulbactam was administered. CONCLUSION: This case underscores the importance of monitoring for bleeding complications and confirming the resolution of rectal lesions before discharging patients from isolation, particularly in cases where patients have a history of engaging in receptive sexual contact with men or are presenting with anal symptoms.

Class VI G protein-coupled receptors in Aspergillus oryzae regulate sclerotia formation through GTPase-activating activity.

G protein-coupled receptors (GPCRs) comprise the largest family of transmembrane receptors in eukaryotes that sense and transduce extracellular signals into cells. In Aspergillus oryzae, 16 canonical GPCR genes are identified and classified into nine classes based on the sequence similarity and proposed functions. Class VI GPCRs (AoGprK-1, AoGprK-2, and AoGprR in A. oryzae), unlike other GPCRs, feature a unique hybrid structure containing both the seven transmembrane (7-TM) and regulator of G-protein signaling (RGS) domains, which is not found in animal GPCRs. We report here that the mutants with double or triple deletion of class VI GPCR genes produced significantly increased number of sclerotia compared to the control strain when grown on agar plates. Interestingly, complementation analysis demonstrated that the expression of the RGS domain without the 7-TM domain is sufficient to restore the phenotype. In line with this, among the three Gα subunits in A. oryzae, AoGpaA, AoGpaB, and AoGanA, forced expression of GTPase-deficient mutants of either AoGpaA or AoGpaB caused an increase in the number of sclerotia formed, suggesting that RGS domains of class VI GPCRs are the negative regulators of these two GTPases. Finally, we measured the expression of velvet complex genes and sclerotia formation-related genes and found that the expression of velB was significantly increased in the multiple gene deletion mutants. Taken together, these results demonstrate that class VI GPCRs negatively regulate sclerotia formation through their GTPase-activating activity in the RGS domains. KEY POINTS: • Class VI GPCRs in A. oryzae regulate sclerotia formation in A. oryzae • RGS function of class VI GPCRs is responsible for regulation of sclerotia formation • Loss of class VI GPCRs resulted in increased expression of sclerotia-related genes.

Supercapatteries as Hybrid Electrochemical Energy Storage Devices: Current Status and Future Prospects.

Among electrochemical energy storage (EES) technologies, rechargeable batteries (RBs) and supercapacitors (SCs) are the two most desired candidates for powering a range of electrical and electronic devices. The RB operates on Faradaic processes, whereas the underlying mechanisms of SCs vary, as non-Faradaic in electrical double-layer capacitors (EDLCs), Faradaic at the surface of the electrodes in pseudo-capacitors (PCs), and a combination of both non-Faradaic and Faradaic in hybrid supercapacitors (HSCs). EDLCs offer high power density but low energy density. HSCs take advantage of the Faradaic process without compromising their capacitive nature. Unlike batteries, supercapacitors provide high power density and numerous charge-discharge cycles; however, their energy density lags that of batteries. Supercapatteries, a generic term that refers to hybrid EES devices that combine the merits of EDLCs and RBs, have emerged, bridging the gap between SCs and RBs. There are numerous articles and reviews on EES, and many of those articles have emphasized various aspects of HSCs and supercapatteries. However, there are no recent reviews that dealt with supercapatteries in general. Here, we review recently published critically selected articles on supercapatteries. The review discusses different EES devices and how supercapatteries are different from others. Also discussed are properties, design strategies, and future perspectives on supercapatteries.

Augmented humoral and cellular immunity against severe acute respiratory syndrome coronavirus 2 after breakthrough infection in kidney transplant recipients who received 3 doses of coronavirus disease 2019 vaccine.

Diminished immune response to coronavirus disease 2019 (COVID-19) vaccines and breakthrough infection (BI) is a major concern for solid organ transplant recipients. Humoral and cellular immune responses of kidney transplant (KT) recipients after a third COVID-19 vaccination were investigated compared to matched health care workers. Anti-severe acute respiratory syndrome coronavirus 2 spike protein antibody and severe acute respiratory syndrome coronavirus 2 specific interferon-gamma releasing assay (IGRA) were assessed. A total of 38 KT recipients, including 20 BI and 18 noninfection, were evaluated. In the KT BI group, antibody titers were significantly increased (median 5 to 724, binding antibody units/mL (P = 0.002) after the third vaccination, but IGRA responses were negligible. After BI, antibody titers increased (median 11 355 binding antibody unit/mL; P < 0.001) and there was a significant increase of IGRA responses to spike proteins (Spike1-Nil, median 0.05 to 0.41 IU/mL; P = 0.009). Antibody titers and IGRA responses were significantly higher in the BI than in the noninfection group after 6 months. Immune responses were stronger in the health care worker than in the KT cohort, but the gap became narrower after BI. In conclusion, KT recipients who experienced BI after 3 COVID-19 vaccinations acquired augmented humoral and cellular immune responses.

Cell selectivity and antibiofilm and anti-inflammatory activities and antibacterial mechanism of symmetric-end antimicrobial peptide centered on D-Pro-Pro.

This study aimed to develop a new symmetric-end antimicrobial peptide (AMP) with cell selectivity, antibiofilm, and anti-inflammatory activities. Two symmetric-end AMPs, Lf6-pP and Lf6-GG, were designed based on the sequence RRWQWRzzRWQWRR, which contains two symmetric repeat sequences connected by a ß-turn-promoting sequence (zz) that can be a rigid turn by D-Pro-Pro (pP) or a flexible turn by Gly-Gly (GG). Both Lf6-pP and Lf6-GG exhibited potent antibacterial activity without causing hemolysis, but Lf6-pP exhibited better cell selectivity, likely due to the more significant impact of the rigid pP turn. Compared to Lf6-GG, Lf6-pP demonstrated approximately three times higher antimicrobial activity against drug-resistant bacteria, had a low incidence of drug resistance, and maintained its activity in the presence of physiological salts and human serum. Additionally, Lf6-pP was more effective than Lf6-GG in inhibiting biofilm formation and eradicating mature biofilms. The BODIPY-cadaverine assay indicated that the potent anti-inflammatory activity of Lf6-pP may be attributed to its direct interaction with LPS, resulting in decreased TNF-α and IL-6 levels in LPS-stimulated macrophages. Mechanistic studies, including membrane depolarization, outer/inner membrane permeation, and membrane integrity change, demonstrated that Lf6-pP exerts its antibacterial action through an intracellular-target mechanism. Overall, we propose that Lf6-pP has potential as a novel antibacterial, antibiofilm, and anti-inflammatory agent against drug-resistant bacterial infections.

Boosting Thermal Conductivity by Surface Plasmon Polaritons Propagating along a Thin Ti Film.

We experimentally demonstrate boosted in-plane thermal conduction by surface plasmon polaritons (SPPs) propagating along a thin Ti film on a glass substrate. Due to the lossy nature of metal, SPPs can propagate over centimeter-scale distances even along a supported metal film, and the resulting ballistic heat conduction can be quantitatively validated. Further, for a 100-nm-thick Ti film on a glass substrate, a significant enhancement of in-plane thermal conductivity compared to bulk value (∼25%) is experimentally shown. This Letter will provide a new avenue to employ SPPs for heat dissipation along a supported thin film, which can be readily applied to mitigate hot-spot issues in microelectronics.

Current Status of Q Fever and the Challenge of Outbreak Preparedness in Korea: One Health Approach to Zoonoses.

Human Q fever, a zoonosis caused by Coxiella burnetii, presents with diverse clinical manifestations ranging from mild self-limited febrile illnesses to life-threatening complications such as endocarditis or vascular infection. Although acute Q fever is a benign illness with a low mortality rate, a large-scale outbreak of Q fever in the Netherlands led to concerns about the possibility of blood transfusion-related transmission or obstetric complications in pregnant women. Furthermore, a small minority (< 5%) of patients with asymptomatic or symptomatic infection progress to chronic Q fever. Chronic Q fever is fatal in 5-50% of patients if left untreated. In South Korea, Q fever in humans was designated as a notifiable infectious disease in 2006, and the number of Q fever cases has increased sharply since 2015. Nonetheless, it is still considered a neglected and under-recognized infectious disease. In this review, recent trends of human and animal Q fever in South Korea, and public health concerns regarding Q fever outbreaks are reviewed, and we consider how a One Health approach could be applied as a preventive measure to prepare for zoonotic Q fever outbreaks.

Gold Standard? Method of Citric Acid Solution Swallowing Test as a Screening Test for Patients with Tracheostomy.

This study aimed to apply various ranges of citric acid levels in the mouth and T-cannula to compare the validity with instrumental aspiration measures in patients with tracheostomy. Sixty-one patients underwent the citric acid cough reflex test (CRT) and videofluoroscopic swallowing study (VFSS). Citric acid was delivered via facemask and T-cannula at concentrations of 0.4 mol/L, 0.6 mol/L, and 0.8 mol/L. Further, we recorded the coughing count and presence of ≥ 2 (C2) and ≥ 5 (C5) coughs. CRT via facemask at 0.4 mol/L C2, 0.6 mol/L C5, and 0.8 mol/L C2 and C5 were significantly associated with the presence of tracheal aspiration during VFSS. The sensitivity and specificity were optimized at 0.8 mol/L C2 for mouth inhalation and at 0.8 mol/L C5 for T-cannula inhalation. There was a significant difference in the coughing count during CRT at 0.4 mol/L and 0.8 mol/L via mouth inhalation between patients with or without tracheal aspiration, but not via T-cannula. The AUC for 0.8 mol/L facemask inhalation was 0.701. The optimal cut-off value of coughing count was thrice with 84.62% sensitivity and 50.00% specificity on the ROC curve. Afferent sensory nerve desensitization around and below the tracheostomy site could affect coughing reflex initiation and decrease the sensitivity of detecting aspiration in tracheotomized patients. The citric acid CRT via facemask can reliably detect tracheal aspiration and presence of coughing reflex compared to that via T-cannula in patients with tracheostomy.

Retear bigger than preoperative tear size would lead to treatment failure after rotator cuff repair.

BACKGROUND: This study aimed to (1) define treatment failure using the referred patient acceptable symptomatic state (PASS) values for pain visual analog scale (PVAS), American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), and Single Assessment Numeric Evaluation (SANE) clinical scores and (2) identify the factors that lead to patient dissatisfaction after arthroscopic rotator cuff repair (ARCR). METHODS: We analyzed the arthroscopic rotator cuff surgery registry data from January 2015 to December 2016. Patients were followed for ≥2 years and categorized as dissatisfied or satisfied based on our own definition of treatment failure at 2 years postoperatively. For defining treatment failure, the referred PASS values for the PVAS, ASES, and SANE scores were used. Patients who failed to attain the PASS value for the PVAS, ASES, or SANE score were categorized into the dissatisfied group. Pre- and postoperative imaging and basic demographic data were compared between groups. Univariable and multivariable logistic regression analyses were performed to identify the factors affecting patient satisfaction at 2 years after rotator cuff repair. RESULTS: Of 117 patients, 30 (25.6%) were defined as the dissatisfied group (mean follow-up period, 37.5 months). Seventeen patients (14.5%) had confirmed retear on follow-up magnetic resonance imaging. In the univariate analysis, sex significantly differed between the groups (female, satisfied vs. dissatisfied groups: 39 [44.8%] vs. 22 [73.3%]; P = .010). Retear alone did not affect patient satisfaction in the univariate analysis (P = .11). Progressed retear size featured a significantly higher risk of patient dissatisfaction (P = .024; odds ratio 6.430, 95% confidence interval 1.270-32.541) in the multivariable analysis using symptom duration, sex, preoperative ASES score, preoperative tear size, retear, and progressed retear size as variables. Moreover, female sex had an increased odds for dissatisfaction (odds ratio 4.646, 95% confidence interval 1.590-13.578; P = .005). CONCLUSION: Two years after ARCR, most patients (74.4%) reported satisfaction with their outcomes. However, satisfaction levels can be altered by female sex or progressed retear size compared with the preoperative state.

Evaluation of the Diagnostic Accuracy of Antibody Assays for Patients with Scrub Typhus.

This study was carried out to evaluate the accuracy of various antibody tests for scrub typhus, namely, the indirect immunofluorescence assay (IFA) from the Korea Centers for Disease Control and Prevention (KCDC) and four commercial kits (companies A to D). The test accuracy was based on the diagnosis of scrub typhus, as defined by a positive PCR or culture. In total, serum samples from 97 patients with scrub typhus and 200 non-scrub typhus patients were tested. The respective sensitivity and specificity of each test were as follows. For the KCDC IFA, sensitivity and specificity were 55.7% (95% confidence interval [CI], 45.2 to 65.8%) and 94.8% (95% CI, 90.4 to 97.3%) for IgM and 42.3% (95% CI, 32.3 to 52.7%) and 96.3% (95% CI, 92.6 to 98.5%) for IgG, with diagnostic cutoffs of ≥1:16 for IgM and ≥1:256 for IgG. For kit A, the sensitivity and specificity were 70.1% (95% CI, 59.8 to 78.8%) and 74.6% (95% CI, 67.6 to 80.6%) for total immunoglobulins, with a cutoff of ≥1:40. For kit B, the sensitivity and specificity were 64.3% (95% CI, 51.9 to 75.1%) and 94.9% (95% CI, 81.4 to 99.1%) for IgM and 67.1% (95% CI, 54.8 to 77.6%) and 74.4% (95% CI, 57.6 to 86.4%) for IgG. For kit C, the sensitivity and specificity were 53.6% (95% CI, 43.2 to 63.7%) and 99.5% (95% CI, 96.8 to 100%) for IgM and 36.1% (95% CI, 26.8 to 46.5%) and 100% (95% CI, 97.6 to 100%) for IgG. For kit D, the sensitivity and specificity were 73.2% (95% CI, 63.1 to 81.4%) and 89.5% (95% CI, 84.2 to 93.2%) for total immunoglobulins. These results are all unsatisfactory, highlighting an urgent need for the development of more highly sensitive and specific tests.

Molecular detection and identification of Culex flavivirus in mosquito species from Jeju, Republic of Korea.

BACKGROUND: Mosquito-borne flaviviruses are prime pathogens and have been a major hazard to humans and animals. They comprise several arthropod-borne viruses, including dengue virus, yellow fever virus, Japanese encephalitis virus, and West Nile virus. Culex flavivirus (CxFV) is a member of the insect-specific flavivirus (ISF) group belonging to the genus Flavivirus, which is widely distributed in a variety of mosquito populations. METHODS: Viral nucleic acid was extracted from adult mosquito pools and subjected to reverse transcriptase nested polymerase chain reaction (PCR) using target-specific primers for detecting CxFV nonstructural protein 5 (NS5). The PCR-positive samples were then sequenced, and a phylogenetic tree was constructed, including reference sequences obtained from GenBank. RESULTS: 21 pools, belonging to Culex pipiens pallens (Cx. p. pallens) were found to be positive for the CxFV RNA sequence, with a minimum infection rate of 14.5/1000 mosquitoes. The phylogenetic analysis of the NS5 protein sequences indicated that the detected sequences were closely related to strains identified in China, with 95-98% sequence similarities. CONCLUSION: Our findings highlight the presence of CxFV in Cx. p. pallens mosquito species in Jeju province, Republic of Korea. This is the first study reporting the prevalence of CxFV in Culex Pipiens (Cx. pipiens) host in the Jeju province, which can create possible interaction with other flaviviruses causing human and animal diseases. Although, mosquito-borne disease causing viruses were not identified properly, more detailed surveillance and investigation of both the host and viruses are essential to understand the prevalence, evolutionary relationship and genetic characteristic with other species.

Potential-Dependent Passivation of Zinc Metal in a Sulfate-Based Aqueous Electrolyte.

Owing to its abundance, high theoretical capacity, and low electrode potential, zinc is one of the most important metallic anodes for primary and secondary batteries such as alkaline and zinc-air batteries. In the operation of zinc-based batteries, passivation of the anode surface plays an essential role because the electrode potential of zinc is slightly below that of the hydrogen evolution reaction. Therefore, it is important to scrutinize the nature of the passivation film to achieve anticorrosion inside batteries. Herein, the potential-dependent formation and removal of the passivation film during the deposition and dissolution of zinc metal in aqueous electrolytes are detected via electrochemical quartz crystal microbalance analysis. Film formation was not noticeable in hydroxide-based electrolytes; however, sulfate-based electrolytes induced potential-dependent formation and removal of the passivation film, enabling a superior coulombic efficiency of 99.37% and significantly reducing the rate of corrosion of the zinc-metal anodes. These observations provide insights into the development of advanced electrolytes for safe and stable energy-storage devices based on zinc-metal anodes.

Label-free fluorometric detection of influenza viral RNA by strand displacement coupled with rolling circle amplification.

Since influenza occurs globally every year, it is important to develop a facile and accurate method to detect the influenza virus. This study aimed at developing a sensitive fluorometric assay for detecting influenza viral RNA through tandem gene amplification methods including reverse transcription PCR (RT-PCR), followed by strand displacement amplification (SDA) coupled with rolling circle amplification (RCA). Influenza viral RNA was initially amplified by RT-PCR with a tailed reverse primer containing an additional sequence for SDA. The RT-PCR amplicon was then subjected to SDA, yielding multiple copies of single-stranded DNA (ssDNA) that can be used as a primer for subsequent RCA. Thereafter, a long ssDNA segment harboring tandem repeated G-quadruplexes that were generated through RCA was intercalated by Thioflavin T, yielding a strong fluorescence signal indicating the presence of the target viral RNA. Fluorometric analysis detected influenza viral RNA ranging from 50 pg to 500 pg with a limit of detection of 6.2 pg with a signal-to-background ratio of 10 and identified each influenza virus strain (H1N1, H3N2, and influenza B). Thus, the present method for the label-free fluorometric detection of viral RNA via tandem gene amplifications combining RT-PCR-coupled SDA and G-quadruplex-generating RCA would facilitate the efficient diagnosis of influenza infection.

Follow-up investigation of antibody titers and diagnostic antibody cutoff values in patients with scrub typhus in South Korea.

BACKGROUND: Scrub typhus is a mite-borne infectious disease caused by Orientia tsutsugamushi. Few follow-up studies have assessed antibody titers using serologic tests from various commercial laboratories and the Korea Centers for Disease Control and Prevention (KCDC). METHODS: A prospective study to assess the antibody titers in patients with scrub typhus and seroprevalence in individuals undergoing health checkups was conducted using results of immunofluorescence antibody assays (IFAs) and serologic tests, used by the KCDC and commercial laboratories, respectively. The following tests were performed simultaneously: (i) indirect IFA used by the KCDC to detect immunoglobulin (Ig) M and IgG, (ii) IFA used by a commercial laboratory to detect total Ig, and (iii) antibody tests using two commercially available kits. RESULTS: When the IgM and IgG cutoff values (≥1:16 and ≥1:256, respectively) used in the IFA and the total IgG cutoff values (≥1:40) were used in prospective follow-up investigations, the antibody positivity rates of 102 patients with scrub typhus were 44.1, 35.3, and 57.6%, respectively, within 5 days of symptom onset. Among 91 individuals who recovered from scrub typhus, the follow-up IgM, IgG, and total Ig positivity rates for 13 years were 37.4% (34/91), 22.0% (20/91), and 76.9% (70/91), respectively. Among 216 individuals undergoing health checkups, the seroprevalence of IgM was 4.2% (9/216); no seroprevalence of IgG was observed. CONCLUSIONS: IFAs used by the KCDC and the commercial laboratory and rapid commercial kits could not distinguish between patients who had recovered from scrub typhus and those who are currently infected with O. tsutsugamushi. In South Korea and other countries, where low antibody cutoff values are used, upward adjustments of cutoff values may be necessary.

Human granulocytic anaplasmosis combined with rhabdomyolysis: a case report.

BACKGROUND: Human granulocytic anaplasmosis (HGA) is a systemic inflammatory response caused by the rickettsial bacterium Anaplasma phagocytophilum. Rhabdomyolysis and acute kidney injury (AKI) are rare complications of HGA. Here, we report a case of HGA concurrent with rhabdomyolysis and AKI in an elderly patient. CASE PRESENTATION: An 84-year old woman with a medical history of hypertension was hospitalised after two days of fever, dizziness, whole body pain, and general weakness. Laboratory investigations showed severe thrombocytopenia, leukopenia, impaired renal function, and elevated cardiac enzyme and myoglobin levels. On the day after admission, peripheral blood smear revealed morula inclusions in neutrophils, a suggestive finding of HGA. Real-time polymerase chain reaction (PCR) results indicated the presence of A. phagocytophilum. Antibiotics were de-escalated to doxycycline monotherapy. After 10 days of antibiotic treatment, laboratory tests showed complete recovery from HGA complicated with rhabdomyolysis and AKI. CONCLUSIONS: HGA can lead to serious complications in patients with associated risk factors. Therefore, in patients with HGA accompanied by rhabdomyolysis, management with antibiotics and hydration should be initiated immediately, and not delayed until diagnostic confirmation.

A case of SFTS coinfected with E. coli bacteremia.

BACKGROUND: Severe fever thrombocytopenia syndrome virus (SFTSV) is the causative agent of severe fever thrombocytopenia syndrome (SFTS). SFTS is an emerging infectious disease, characterized by high fever, gastrointestinal symptoms, leukopenia, thrombocytopenia, and a high mortality rate. Until now, little importance has been given to the association of SFTS with leukocytosis and bacterial co-infection. CASE PRESENTATION: A 51-year old man visited our hospital with fever and low blood pressure. He was a farmer by occupation and often worked outdoors. He had a Foley catheter inserted due to severe BPH. Laboratory tests revealed thrombocytopenia, elevated liver function, and elevated CRP levels. He had marked leukocytosis, proteinuria, hematuria, and conjunctival hemorrhage. Initially, we thought that the patient was suffering from hemorrhagic fever with renal syndrome (HFRS). However, we confirmed SFTS through PCR and increasing antibody titer. However, his blood culture also indicated E. coli infection. CONCLUSION: SFTS displays characteristics of fever, thrombocytopenia, elevated liver function, and leukocytopenia. We described a case of SFTS with leukocytosis due to coinfection with E. coli. Since patients with SFTS usually have leukocytopenia, SFTS patients with leukocytosis are necessarily evaluated for other causes of leukocytosis. Here, we report the first case of an SFTS with concurrent E. coli bacteremia.

Veno-arterial extracorporeal membrane oxygenation for severe fever with thrombocytopenia syndrome with fulminant myocarditis: a case report.

BACKGROUND: The clinical spectrum of severe fever with thrombocytopenia syndrome (SFTS) is wide, which can range from fever to multiple organ failure. Conservative therapy plays a key role in the treatment of SFTS. However, severe cases of SFTS, such as fulminant myocarditis, may require mechanical hemodynamic support. CASE PRESENTATION: This report presents a case of a 59-year old woman diagnosed with SFTS by reverse-transcription polymerase chain reaction. The patient had no initial symptoms of cardiac involvement and rapidly developed hemodynamic instability 3 days after hospitalization. She suffered from chest pain and had elevated cardiac enzymes. In the absence of atrio-ventricular conduction abnormalities, left ventricular dysfunction, and coronary artery abnormalities by coronary angiography, she was diagnosed with fulminant myocarditis. At that time, her pulse rate nearly dropped to 0 bpm and she developed near complete akinesia of the heart despite vasopressor administration. Veno-arterial extracorporeal membrane oxygenation (ECMO) was initiated with other supportive measures and she fully recovered after 21 days. CONCLUSIONS: This case indicates that SFTS can cause fulminant myocarditis even without evidence of cardiac involvement at presentation. When symptoms and/or signs of acute heart failure develop in patients with SFTS, myocarditis should be suspected and the patient should be promptly evaluated. Additionally, mechanical hemodynamic support like ECMO can be a lifesaving tool in the treatment of fulminant myocarditis.

Role of p53 in transcriptional repression of SVCT2.

SVCT2, Sodium-dependent Vitamin C Transporter 2, uniquely transports ascorbic acid (also known as vitamin C and ascorbate) into all types of cells. Vitamin C is an essential nutrient that must be obtained through the diet and plasma levels are tightly regulated by transporter activity. Vitamin C plays an important role in antioxidant defenses and is a cofactor for many enzymes that enable hormone synthesis, oxygen sensing, collagen synthesis and epigenetic pathways. Although SVCT2 has various functions, regulation of its expression/activity remains poorly understood. We found a p53-binding site, within the SVCT2 promoter, using a transcription factor binding-site prediction tool. In this study, we show that p53 can directly repress SVCT2 transcription by binding a proximal- (~-185 to -171 bp) and a distal- (~-1800 to -1787 bp) p53-responsive element (PRE), Chromatin immunoprecipitation assays showed that PRE-bound p53 interacts with the corepressor-histone deacetylase 3 (HDAC3), resulting in deacetylation of histones Ac-H4, at the proximal promoter, resulting in transcriptional silencing of SVCT2. Overall, our data suggests that p53 is a potent transcriptional repressor of SVCT2, a critical transporter of diet-derived ascorbic acid, across the plasma membranes of numerous essential tissue cell types.