Sirtuin 3 Mediated by Spinal cMyc-Enhancer of Zeste Homology 2 Pathway Plays an Important Role in Human Immunodeficiency Virus-Related Neuropathic Pain Model.

BACKGROUND: Clinical data demonstrate that chronic use of opioid analgesics increases neuropathic pain in people living with human immunodeficiency virus (HIV). Therefore, it is important to elucidate the molecular mechanisms of HIV-related chronic pain. In this study, we investigated the role of the transcription factor cMyc, epigenetic writer enhancer of zeste homology 2 (EZH2), and sirtuin 3 (Sirt3) pathway in HIV glycoprotein gp120 with morphine (gp120M)-induced neuropathic pain in rats. METHODS: Neuropathic pain was induced by intrathecal administration of recombinant gp120 with morphine. Mechanical withdrawal threshold was measured using von Frey filaments, and thermal latency using the hotplate test. Spinal expression of cMyc, EZH2, and Sirt3 were measured using Western blots. Antinociceptive effects of intrathecal administration of antisense oligodeoxynucleotide against cMyc, a selective inhibitor of EZH2, or recombinant Sirt3 were tested. RESULTS: In the spinal dorsal horn, gp120M upregulated expression of cMyc (ratio of gp120M versus control, 1.68 ± 0.08 vs 1.00 ± 0.14, P = .0132) and EZH2 (ratio of gp120M versus control, 1.76 ± 0.05 vs 1.00 ± 0.16, P = .006), and downregulated Sirt3 (ratio of control versus gp120M, 1.00 ± 0.13 vs 0.43 ± 0.10, P = .0069) compared to control. Treatment with intrathecal antisense oligodeoxynucleotide against cMyc, GSK126 (EZH2 selective inhibitor), or recombinant Sirt3 reduced mechanical allodynia and thermal hyperalgesia in this gp120M pain model. Knockdown of cMyc reduced spinal EZH2 expression in gp120M treated rats. Chromatin immunoprecipitation (ChIP) assay showed that enrichment of cMyc binding to the ezh2 gene promoter region was increased in the gp120M-treated rat spinal dorsal horn, and that intrathecal administration of antisense ODN against cMyc (AS-cMyc) reversed the increased enrichment of cMyc. Enrichment of trimethylation of histone 3 on lysine residue 27 (H3K27me3; an epigenetic mark associated with the downregulation of gene expression) binding to the sirt3 gene promoter region was upregulated in the gp120M-treated rat spinal dorsal horn; that intrathecal GSK126 reversed the increased enrichment of H3K27me3 in the sirt3 gene promoter. Luciferase reporter assay demonstrated that cMyc mediated ezh2 gene transcription at the ezh2 gene promoter region, and that H3K27me3 silenced sirt3 gene transcription at the gene promoter region. CONCLUSION: These results demonstrated that spinal Sirt3 decrease in gp120M-induced neuropathic pain was mediated by cMyc-EZH2/H3K27me3 activity in an epigenetic manner. This study provided new insight into the mechanisms of neuropathic pain in HIV patients with chronic opioids.

Polyhydroxybutyrate (PHB) production from sugar cane molasses and tap water without sterilization using novel strain, Priestia sp. YH4.

The production cost of biodegradable polymer like polyhydroxybutyrate (PHB) is still higher than that of petroleum-based plastics. A potential solution for reducing its production cost is using a cheap carbon source and avoiding a process of sterilization. In this study, a novel PHB-producing microbial strain, Priestia sp. YH4 was screened from the marine environment using sugarcane molasses as the carbon source without sterilization. Culture conditions, such as carbon, NaCl, temperature, pH, inoculum size, and cultivation time, were optimized for obtaining the highest PHB production by YH4 resulting in 5.94 g/L of dry cell weight (DCW) and 61.7 % of PHB content in the 5 mL culture. In addition, it showed similar PHB production between the cultures with or without sterilization in Marine Broth media. When cultured using only tap water, sugarcane molasses, and NaCl in a 5 L fermenter, 24.8 g/L DCW was produced at 41 h yielding 13.9 g/L PHB. Finally, DSC (Differential Scanning Calorimetry) and GPC (Gel Permeation Chromatography) were used to analyze thermal properties and molecular weights resulting in Tm = 167.2 °C, Tc = 67.3 °C, Mw = 2.85 × 105, Mn = 1.05 × 105, and PDI = 2.7, respectively. Therefore, we showed the feasibility of more economical process for PHB production by finding novel strain, utilizing molasses with minimal media components and avoiding sterilization.

Impact of the Coronavirus Disease Pandemic on Mental Health Among School Students in Korea During the COVID-19 Pandemic.

Objectives: The coronavirus disease (COVID-19) pandemic has had various effects on mankind, especially children and adolescents. Because children and adolescents spend a lot of time at school, COVID-19 has had a great impact on school mental health. In this study, we investigated the effect of prolonged COVID-19 on school mental health. Methods: We prepared self-report questionnaires for depression (Children's Depression Inventory, CDI), anxiety (Korean version of the Penn State Worry Questionnaire for Children; Generalized Anxiety Disorder-7, GAD-7), and post-traumatic stress (Primary Care Post-traumatic Stress Disorder, PC-PTSD) for administering to students aged between 7 and 18 years, recruited by a COVID-19 psychological prevention support group in the Gwangmyeong Mental Health Welfare Center for 2 years, in 2020 and 2021. Results: For children aged 7-12 years, there was no significant difference between the years 2020 and 2021 in the assessment of depression, anxiety, and post-traumatic stress. Conversely, for adolescents aged 13-18 years, there was a significant increase in the scale scores (CDI, PC-PTSD, and GAD-7). Conclusion: Prolonged COVID-19 might have had a significant impact on the mental health of adolescents who spent a lot of time at school. When comparing the years 2020 and 2021, middle and high school students were more affected by COVID-19 than elementary school students.

Medic and Portable Pulse Oximeter Respiratory Rate Measurement Comparison to Waveform Capnography: A Prospective, Observational Study.

BACKGROUND: The second leading cause of preventable battlefield death involves airway management. Tactical combat casualty care (TCCC) guidelines emphasize combat casualty airway, breathing and respiratory evaluation, including respiratory rate (RR) measurement. The current standard of practice for the US Army medics is to measure the RR by manual counting. Manual counting methods are operator-dependent, and medics face situational stressors limiting accurate measurement of RR in combat settings. To date, no published studies evaluate alternate methods of RR measurement by medics. The purpose of this study is to compare RR assessment by medics against waveform capnography and commercial finger pulse oximeters with continuous plethysmography. MATERIALS AND METHODS: We conducted a prospective, observational study to compare Army medic RR assessments against plethysmography and waveform capnography RR. Assessments were performed prior to and following exertion at 30 and 60 seconds with both the pulse oximeter (NSN 6515-01-655-9412) and defibrillator monitor (NSN 6515-01-607-8629), followed by end-user surveys. RESULTS: Of the 40 medics enrolled over a 4-month period, most were male (85%), and reported between less than 5 years of military and medical experience. The mean manual RR reported by medics at rest did not significantly differ from waveform capnography (14.05 versus 13.98, p is equal to 0.523); however, mean manual RR reported by medics on post-exertional subjects was significantly lower than waveform capnography (25.62 versus 29.77, p is less than 0.001). Time to medic-obtained RR was slower than the pulse oximeter (NSN 6515-01-655-9412) both at rest (-7.37 seconds, p is less than 0.001) and at exertion (-6.50 seconds, p is less than 0.001). While the mean difference in RR between the pulse oximeter (NSN 6515-01-655-9412) and waveform capnography in models at rest at 30 seconds was statistically significant (-1.38, p is less than 0.001). There was no overall statistically significant differences in RR between the pulse oximeter (NSN 6515-01-655-9412) and waveform capnography in models at exertion at 30 seconds and at rest and exertion at 60 seconds. CONCLUSION: Resting RR measurement did not differ significantly; however, medic-obtained RR considerably deviated from both pulse oximeters and waveform capnography at elevated rates. Existing commercial pulse oximeters with RR plethysmography do not differ significantly from waveform capnography and should be investigated further for consideration in fielding across the force for RR assessment.

Causing trouble and being transmissible: COVID-19 survivors' experiences of stigma and discrimination in South Korea.

Background: The stigma associated with coronavirus disease (COVID-19) is relatively neglected in policies for handling the disease. Stigmatization occurs only within specific social contexts in local societies. Objective: This study aims to examine COVID-19 survivors' experiences of social stigma and discrimination in South Korea in the first 2 years of the pandemic. Methods: Semi-structured interviews were conducted. Results: Of 52 participants, 45 reported that they had to cope with stigma and discrimination in their intimate social relationships, workplaces, and children's schools, ranging from subtle actions to job loss. Sexual minorities who were involved in mass disease transmission in the early part of the pandemic experienced a higher level of stigmatization. The stigmatization dealt with in this study was related to two themes: survivors' sense of causing trouble and possibility of transmission. Conclusion: By intertwining this stigma with the experiences of public health measures through the voices of survivors, this study reveals the local context of East Asia in terms of culture-specific aspects of COVID-19-related stigma.

Role of Tumor Necrosis Factor Receptor 1-Reactive Oxygen Species-Caspase 11 Pathway in Neuropathic Pain Mediated by HIV gp120 With Morphine in Rats.

BACKGROUND: Recent clinical research suggests that repeated use of opioid pain medications can increase neuropathic pain in people living with human immunodeficiency virus (HIV; PLWH). Therefore, it is significant to elucidate the exact mechanisms of HIV-related chronic pain. HIV infection and chronic morphine induce proinflammatory factors, such as tumor necrosis factor (TNF)α acting through tumor necrosis factor receptor I (TNFRI). HIV coat proteins and/or chronic morphine increase mitochondrial superoxide in the spinal cord dorsal horn (SCDH). Recently, emerging cytoplasmic caspase-11 is defined as a noncanonical inflammasome and can be activated by reactive oxygen species (ROS). Here, we tested our hypothesis that HIV coat glycoprotein gp120 with chronic morphine activates a TNFRI-mtROS-caspase-11 pathway in rats, which increases neuroinflammation and neuropathic pain. METHODS: Neuropathic pain was induced by repeated administration of recombinant gp120 with morphine (gp120/M) in rats. Mechanical allodynia was assessed using von Frey filaments, and thermal latency using hotplate test. Protein expression of spinal TNFRI and cleaved caspase-11 was examined using western blots. The image of spinal mitochondrial superoxide was examined using MitoSox Red (mitochondrial superoxide indicator) image assay. Immunohistochemistry was used to examine the location of TNFRI and caspase-11 in the SCDH. Intrathecal administration of antisense oligodeoxynucleotide (AS-ODN) against TNFRI, caspase-11 siRNA, or a scavenger of mitochondrial superoxide was given for antinociceptive effects. Statistical tests were done using analysis of variance (1- or 2-way), or 2-tailed t test. RESULTS: Intrathecal gp120/M induced mechanical allodynia and thermal hyperalgesia lasting for 3 weeks ( P < .001). Gp120/M increased the expression of spinal TNFRI, mitochondrial superoxide, and cleaved caspase-11. Immunohistochemistry showed that TNFRI and caspase-11 were mainly expressed in the neurons of the SCDH. Intrathecal administration of antisense oligonucleotides against TNFRI, Mito-Tempol (a scavenger of mitochondrial superoxide), or caspase-11 siRNA reduced mechanical allodynia and thermal hyperalgesia in the gp120/M neuropathic pain model. Spinal knockdown of TNFRI reduced MitoSox profile cell number in the SCDH; intrathecal Mito-T decreased spinal caspase-11 expression in gp120/M rats. In the cultured B35 neurons treated with TNFα, pretreatment with Mito-Tempol reduced active caspase-11 in the neurons. CONCLUSIONS: These results suggest that spinal TNFRI-mtROS-caspase 11 signal pathway plays a critical role in the HIV-associated neuropathic pain state, providing a novel approach to treating chronic pain in PLWH with opioids.

Perception and Experience of Sexual and Gender Minority Korean Youth in School Counseling.

To comprehensively explore the school counseling experience of sexual and gender minority (SGM) youths in South Korea, we interviewed 14 SGM youths about their school counseling experience and the climate of their schools toward SGM. Results showed that a hostile school climate and the accessibility, confidentiality, trustworthiness, and LGBTQ competency of school counselors drove the reluctance of these youths to receive school counseling services. Implications for the role of school counseling services for SGM youths were discussed based on the findings of this work and the suggestions offered by the interviewed SGM youths. Supplementary Information: The online version contains supplementary material available at 10.1007/s10447-022-09490-0.

Clinical Utility of the Portable Pressure-Measuring Device for Compression Garment Pressure Measurement on Hypertrophic Scars by Burn Injury during Compression Therapy.

Compression therapy for burn scars can accelerate scar maturation and improve clinical symptoms (pruritus and pain). This study objectively verified the effect of pressure garment therapy in maintaining a therapeutic pressure range for hypertrophic scars. Sixty-five participants (aged 20~70 years) with partial- or full-thickness burns, Vancouver scar scale score of ≥4, and a hypertrophic scar of ≥4 cm × 4 cm were enrolled. Compression pressure was measured weekly using a portable pressure-monitoring device to regulate this pressure at 15~25 mmHg for 2 months. In the control group, the compression garment use duration and all other burn rehabilitation measures were identical except for compression monitoring. No significant difference was noted in the initial evaluations between the two groups (p > 0.05). The improvements in the amount of change in scar thickness (p = 0.03), erythema (p = 0.03), and sebum (p = 0.02) were significantly more in the pressure monitoring group than in the control group. No significant differences were noted in melanin levels, trans-epidermal water loss, or changes measured using the Cutometer® between the two groups. The efficacy of compression garment therapy for burn-related hypertrophic scars can be improved using a pressure-monitoring device to maintain the therapeutic range.

Smartphone Usage and Sleep Quality in Korean Middle School Students During the COVID-19 Pandemic.

OBJECTIVE: This study evaluated the quality of sleep and smartphone addiction in Korean adolescents during the coronavirus disease 19 pandemic and analyzed their effects on perceived quality of life. METHODS: An online survey system provided by the Gwangmyeong City Health Center located in Gyeonggi-do, Korea, was completed by 1,678 local middle school students from April 1 to June 30, 2021. We measured quality of life using the KIDSCREEN-27 health-related quality of life questionnaire, quality of sleep using the Korean version of the Pittsburgh Sleep Quality Index, and smartphone addiction using the Smartphone Addiction Self-Diagnosis Scale. Bed times, wake times, and total sleep hours were also recorded. RESULTS: Sleep quality and quantity were directly associated with smartphone addiction. The results indicated that lower quality of life was associated with lower sleep quality, delayed onset of sleep, shorter total sleep time, and higher smartphone addiction. Female students reported lower quality of life, lower sleep quality, delayed sleep phases, shorter total sleep hours, and higher smartphone addiction scores than did male students. CONCLUSION: Our results suggest that adolescents' quality of life is threatened by poor sleep, which in turn could be due to unhealthy smartphone usage. Girls were more heavily affected by this trend than were boys. Preparations to intervene for further mental health issues that might follow are necessary.

Lymphoma total lesion glycolysis leads to hyperlactatemia and reduction of brain glucose utilization.

Clarifying the mechanism of lymphoma-associated hyperlactatemia could help identify patients at risk. Here, 129 non-Hodgkin's lymphoma patients suspected of blood lactate elevation underwent blood measurement and 18F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) on the same day. Blood lactate elevation was mild (1.0-2.5 mmol/L) in 60, moderate (2.5-4.0 mmol/L) in 46, and severe (≥ 4.0 mmol/L) in 23 subjects. Subjects with severe lactate elevation had higher lymphoma stage, worse IPI risk, poorer ECOG performance, and higher tumor TLG. Furthermore, there was a linear correlation between blood lactate concentration and lymphoma TLG (Spearman's r = 0.367; P < 0.0001). Brain FDG uptake was low (SUVave < 4.0) in 81 patients that were older, had greater stage and IPI risk, worse ECOG performance, and higher blood lactate. Brain SUVave showed inverse correlation with blood lactate (Spearman's r = - 0.564; P < 0.0001) and lymphoma TLG (Spearman's r = - 0.252; P = 0.0066), as well as with stage, ECOG score, and IPI risk. Multivariable regression analysis confirmed increased blood lactate and lymphoma TLG as significant explanatory variables for reduced brain SUVave (both P < 0.0001). Hence, blood lactate elevation in lymphoma patients is the result of glycolytic tumor burden. Since brain cells prefer lactate over glucose as energy source when blood lactate level is increased, this causes proportional reductions of brain FDG uptake. FDG PET/CT can therefore identify high glycolytic lymphoma burden at risk of hyperlactatemia and may provide estimates of its severity by reductions in brain uptake.

Hypertriglyceridemia-Induced Pancreatitis and a Lipemic Blood Sample: A Case Report and Brief Clinical Review.

Hypertriglyceridemia is the third most common cause of acute pancreatitis after gallstones and long-term alcohol use. There are specific therapeutic options unique to hyperglyceridemia-induced pancreatitis, such as continuous insulin therapy and plasmapheresis, emphasizing the importance of identifying hypertriglyceridemia as the cause. Triglyceride levels > 1000 mg/dL may result in a visibly lipemic blood sample. Lipemic samples may interfere with laboratory equipment, resulting in erroneous levels or the inability to measure several serum blood tests. Consider hypertriglyceridemia as a cause for acute pancreatitis in the setting of a lipemic blood sample or when gallstones have been excluded.

A lethargic child with COVID-19 infection.

ABSTRACT: COVID-19 infection in children is less understood than COVID-19 infection in adults, and although it is believed to cause mild or asymptomatic infections, several cases of severe or atypical presentations have been reported. Children presenting with gastrointestinal symptoms, even those without respiratory symptoms, should raise the suspicion for possible COVID-19 infection. This case report describes a 20-month-old girl with a clear history of COVID-19 exposure whose acute abdomen and lethargy were diagnosed as COVID-19 infection complicated by intussusception.

Impact of the Coronavirus Disease Pandemic on Mental Health among Local Residents in Korea: a Cross Sectional Study.

BACKGROUND: This study aimed to evaluate traumatic stress and mental health problems associated with the prolonged coronavirus disease pandemic and to determine the differences across different age groups. METHODS: A total of 1,151 individuals who visited Gwangmyeong City Mental Health Welfare Center, South Korea, or accessed the website from September 1 to December 31, 2020, were included in the study. Mental health problems such as traumatic stress (Primary Care Posttraumatic Stress Disorder Screen for the Diagnostic and Statistical Manual of Mental Disorder-5); depression (Patient Health Questionnaire-9 and Children's Depression Inventory); anxiety (Generalized Anxiety Disorder-7 and Penn State Worry Questionnaire for Children); suicide risk (P4 Screener); and demographic information were evaluated. The participants were divided into three groups based on age group: children and adolescents, adults, and the elderly. RESULTS: The results showed that 24.7%, 20.9%, 16.8%, and 20.5% of the participants were at high-risk for traumatic stress, depression, anxiety, and suicide, respectively. The difference in the proportion of high-risk groups by age of all participants was significant for traumatic stress, depression, anxiety, and suicide risk. In particular, the percentage of high-risk groups in all areas was the highest in the adult group. Also, in most areas, the ratio of the high-risk groups for children and adolescent group was the lowest, but the suicide risk-related ratio was not (adolescent group: 20.9%, adult group: 25%, elderly group 9.3%). CONCLUSION: These results suggest that there is a need for continued interest in the mental health of the general population even after the initial period of coronavirus disease. Additionally, this study may be helpful when considering the resilience or risk factors of mental health in a prolonged disaster situation.

Alleles disrupting LBD37-like gene by an 136 bp insertion show different distributions between green and purple cabbages (Brassica oleracea var. capitata).

BACKGROUND: In Arabidopsis thaliana (Arabidopsis), clade IIb lateral organ boundary domain (LBD) 37, 38, and 39 proteins negatively regulate anthocyanin biosynthesis and affect nitrogen responses. OBJECTIVE: To investigate the possible role of LBD genes in anthocyanin accumulations among green and purple cabbages (Brassica oleracea var. capitata), we determined sequence variations and expression levels of cabbage homologs of Arabidopsis LBD37, 38, and 39. METHODS: DNA and mRNA sequences of BoLBD37, BoLBD37L (BoLBD37-like), BoLBD38, BoLBD38L (BoLBD38-like), and BoLBD39 gene in cabbage were determined. Allelic variations of BoLBD37L alleles in cabbages, resulting from insertions, were validated by genomic DNA PCR. Gene expressions were examined by semi-quantitative reverse transcription (RT-PCR) or quantitative RT-PCR. RESULTS: Based on the expression analyses, BoLBD37L with two alleles, BoLBD37L-G and BoLBD37L-P, was selected as a candidate gene important for differential anthocyanin accumulation. BoLBD37L-P contains an 136 base pair insertion in the 2nd exon, producing two splicing variants encoding truncated proteins. Most purple cabbage lines were found to have BoLBD37L-P allele as homozygotes or heterozygotes, and only two out of sixty-four purple cabbages were identified as BoLBD37L-G homozygotes. Expression analyses of anthocyanin biosynthesis genes and their upstream regulators, including BoLBD37L, suggest that truncated proteins encoded by splicing variants of BoLBD37L-P may disrupt the BoLBD37L function as repressor. CONCLUSION: Difference in the C-terminal region of BoLBD37L-G and BolBD37L-P may affect the expression of downstream genes, BoMYB114L and BoTT8, resulting in differential anthocyanin accumulation.

Effects of Community-Based Interventions on Medication Adherence and Hospitalization for Elderly Patients with Type 2 Diabetes at Primary Care Clinics in South Korea.

Korean Disease Control and Prevention Agency launched Control and Prevention Community-based Registration and Management for Hypertension and Diabetes mellitus Project (CRMHDP) in Gwangmyeong city, 2009. This project has provided incentives on both patient and physician and has made private clinics and Public Health Center (PHC) in a community collaborate for effective chronic disease management among elderly people. This study aimed to evaluate the effects of CRMHDP on medication compliance and hospitalization due to diabetes-specific complications. The retrospective cohort study design was based on data of Korean National Health Insurance (KNHI) with 2 control areas (A & B) with usual primary care service similar to Gwangmyeong city regarding community health resources. The data on the study subjects were examined for the following 5 years since the baseline point. Medication adherence rates of CRMHDP-enrollees after the project was significantly higher than two control groups. For the hospitalization due to any complications, adjusted hazard ratio in the intervention group, compared to the control group A and B, were 0.76 (95% Confidence Interval: 0.65-0.78) and 0.52 (95% Confidence Interval 0.41-0.78), respectively. CRMHDP could successful in improving the management of type 2 diabetes mellitus among elderly people in South Korean primary care settings.

Viral vector-mediated gene therapy for opioid use disorders.

Chronic exposure to opioids typically results in adverse consequences. Opioid use disorder (OUD) is a disease of the CNS with behavioral, psychological, neurobiological, and medical manifestations. OUD induces a variety of changes of neurotransmitters/neuropeptides in the nervous system. Existing pharmacotherapy, such as opioid maintenance therapy (OMT) is the mainstay for the treatment of OUD, however, current opioid replacement therapy is far from effective for the majority of patients. Pharmacological therapy for OUD has been challenging for many reasons including debilitating side-effects. Therefore, developing an effective, non-pharmacological approach would be a critical advancement in improving and expanding treatment for OUD. Viral vector mediated gene therapy provides a potential new approach for treating opioid abused patients. Gene therapy can supply targeting gene products directly linked to the mechanisms of OUD to restore neurotransmitter and/or neuropeptides imbalance, and avoid the off-target effects of systemic administration of drugs. The most commonly used viral vectors in rodent studies of treatment of opioid-used disorder are based on recombinant adenovirus (AV), adeno-associated virus (AAV), lentiviral (LV) vectors, and herpes simplex virus (HSV) vectors. In this review, we will focus on the recent progress of viral vector mediated gene therapy in OUD, especially morphine tolerance and withdrawal.

Mitochondrial biogenesis factor PGC-1α suppresses spinal morphine tolerance by reducing mitochondrial superoxide.

Opioid use disorders (OUDs) have reached an epidemic level in the United States. The opioid epidemic involves illicit opioid use, prescription opioids for analgesia, counterfeit opioids, new psychoactive substances, and diverted opioids. Opioids remain the last option for the treatment of intractable clinical pain, but chronic use of opioids are limited in part due to antinociceptive/analgesic tolerance. Peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1alpha (PGC-1α), a mitochondrial biogenesis factor can reduce toxic reactive oxygen species (ROS) that play a role in morphine tolerance (MT). Decreased PGC-1α expression has been shown to contribute to various metabolic disorders or neurodegeneration diseases through increasing ROS. We examined the relationship of PGC-1α and ROS in MT. To induce MT, adult Sprague-Dawley rats received intrathecal morphine for 7 days. Mechanical threshold was measured using the von Frey test and thermal latency was examined using the heat plate test. Expression of PGC-1α in the spinal cord dorsal horn (SCDH) was examined using RT-PCR and western blots. Mitochondrial superoxide was detected using MitoSox Red, a mitochondrial superoxide indicator. The antinociceptive effect of recombinant PGC-1α (rPGC-1α) or Mito-Tempol (a mitochondria-targeted superoxide scavenger) was determined using the von Frey test and hot plate test. Furthermore, we examined the effect of rPGC-1α on mitochondrial superoxide using cultured neurons. Our findings include that: (i) spinal MT decreased the expression of spinal PGC-1α in the SCDH neurons; (ii) rPGC-1α increased mechanical threshold and thermal latency in MT animals; (iii) Mito-Tempol reduced MT behavioral response; (iv) rPGC-1α reduced MT-induced mitochondria-targeted superoxide; and (v) cultured neuronal cells treated with TNFα increased mitochondria-targeted superoxide that can be inhibited by rPGC-1α. The present findings suggest that spinal PGC-1α reduce MT through decreasing mitochondria-targeted superoxide in the SCDH.

Direct detection of SARS-CoV-2 RNA using high-contrast pH-sensitive dyes.

The worldwide coronavirus disease 2019 pandemic has had devastating effects on health, healthcare infrastructure, social structure, and economics. One of the limiting factors in containing the spread of this virus has been the lack of widespread availability of fast, inexpensive, and reliable methods for testing of individuals. Frequent screening for infected and often asymptomatic people is a cornerstone of pandemic management plans. Here, we introduce 2 pH-sensitive "LAMPshade" dyes as novel readouts in an isothermal Reverse Transcriptase Loop-mediated isothermal AMPlification amplification assay for severe acute respiratory syndrome coronavirus 2 RNA. The resulting JaneliaLAMP assay is robust, simple, inexpensive, and has low technical requirements, and we describe its use and performance in direct testing of contrived and clinical samples without RNA extraction.

The role of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography in the differential diagnosis of pericardial disease.

This study aimed to assess the role of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG-PET/CT) in the differential diagnosis of pericardial disease. The diagnosis is often troublesome because pericardial fluid analysis or biopsy does not always provide answers. 18FDG-PET/CT can visualize both inflammation and malignancy and offers a whole-body assessment. Patients who visited the Pericardial Disease Clinic of Samsung Medical Center with an 18FDG-PET/CT order code were extracted. Exclusion criteria were as follows: (1) the purpose of the differential diagnosis was not pericardial disease; (2) the patient had a known advanced-stage malignancy; (3) the patient already have confirmative diagnosis using a serology, pericardial effusion analysis or biopsy. The analysis included 107 patients. The most common final diagnosis was idiopathic (n = 46, 43.0%), followed by tuberculosis (n = 30, 28.0%) and neoplastic (n = 11, 10.3%). A maximum standardized uptake value (SUVmax) ≥ 5 typically indicates tuberculosis or neoplastic pericarditis except in just one case of autoimmune pericarditis); especially all of the SUVmax scores ≥ 10 had tuberculosis. The diagnostic yield of pericardial biopsy was very low (10.2%). Interestingly, all of the pericardium with an SUVmax < 4.4 had nondiagnostic results. In contrast, targeted biopsies based on 18FDG uptake demonstrated a higher diagnostic yield (38.7%) than pericardium. The sensitivity of 18FDG-PET/CT was 63.6%. The specificity was 71.9%. The positive predictive value was 20.6%. The negative predictive value 94.5%, and the accuracy was 71.0% for excluding malignancy based upon the FDG uptake patterns. It is possible to explore the differential diagnosis in some patients with difficult pericardiocentesis or pericardial biopsy in a noninvasive manner using on the SUVmax or uptake patterns. In addition, the biopsy strategy depending on 18FDG uptake is helpful to achieve biopsy more safely and with a higher yield. 18FDG-PET may enhance the diagnostic efficacy in patients with pericardial disease.

Total FDG lesion number on PET/CT predicts survival of esophageal carcinoma patients with recurrence following curative surgery.

BACKGROUND: Total lesion number is a prognostic determinant in recurrent esophageal cancer, but this requires multiple tests. Here, we investigated the prognostic value of total FDG lesion number obtained from a single PET/CT study. METHODS: Subjects were 153 esophageal squamous cell carcinoma patients with loco-regional or distant recurrence following curative surgery. FDG PET/CT performed within 30 days was inspected for abnormal FDG uptake lesions using a SUVmax of 3.0 as threshold for significance. Prognostic associations were assessed by Cox proportional hazards regression and Kaplan-Meier analysis. RESULTS: PET/CT showed significant local FDG lesions in 49.0%, regional lesions in 78.4%, and distant lesions in 44.4% of patients. Among 73 patients with loco-regional recurrence, 54 had 0-3 and 19 had ≥4 FDG lesions. Among 80 patients with distant recurrence, 31 had 0-3 and 49 had ≥4 FDG lesions. During a median follow-up of 11.8 months, 99 deaths occurred. Univariate variables associated with poor survival included ≥4 FDG lesions and no treatment for loco-regional recurrence and no treatment for distant recurrence. Kaplan Meier analysis showed worse survival for ≥4 than 0-3 FDG lesions in patients with loco-regional recurrence (15.6 vs. 32.1 months; P=0.009), but not in those with distant recurrence. Significant independent predictors of poor survival were ≥4 FDG lesions and no treatment for loco-regional recurrence and no treatment for distant recurrence. CONCLUSIONS: Total FDG lesion number assessed by PET/CT is a significant independent prognostic factor in esophageal cancer patients with loco-regional recurrence following curative surgery.