Translocator protein 18 kDa (TSPO) is a mitochondrial protein highly expressed on reactive microglia and astrocytes, and is considered as a biomarker for neurodegeneration and brain damage, especially neuroinflammation. Toll-like receptors (TLRs) are closely related with inflammatory responses of microglia and astrocytes and these signaling pathways regulate neuroinflammation. Previous reports have identified the anti-inflammatory effects of TSPO ligands, however study of their effects in relation to the TLR signaling was limited. Here, we investigated the effects of five representative TSPO ligands on microglia and astrocytes following activation by various TLR ligands. Our results show that TSPO ligands reduce the pro-inflammatory response elicited by the TLR ligands with more profound effects on microglia than astrocytes.
Astrocytes* ; Brain ; Ligands* ; Microglia* ; Mitochondrial Proteins ; Toll-Like Receptors

Allogeneic hematopoietic stem cell transplantation (HSCT) may not be considered feasible in a patient with active fungal infection due to transplant-related mortality. We report a case of HSCT performed on a 6-month-old girl, who was diagnosed with very severe aplastic anemia (vSAA) at the age of 2 months, during active invasive pulmonary aspergillosis (IPA). Despite receiving continuous antifungal treatment and multiple granulocyte infusions, her IPA was aggravated. She underwent allogeneic HSCT from a matched sibling donor using conditioning regimen of fludarabine, reduced dose of cyclophosphamide, and anti-thymocyte globulin (ATG) during IPA. After neutrophil engraftment, fever subsided and IPA improved. She was continued on voriconazole for 7 months after HSCT. She is alive with normal hematopoiesis 4 years post-transplant. Our report suggests that allogeneic HSCT using conditioning regimen of fludarabine, reduced dose of cyclophosphamide, and ATG can be a feasible option for the patients with vSAA even during active fungal infection.
Anemia, Aplastic ; Antilymphocyte Serum ; Cyclophosphamide ; Female ; Fever ; Granulocytes ; Hematopoiesis ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Infant ; Invasive Pulmonary Aspergillosis ; Mortality ; Neutrophils ; Siblings ; Tissue Donors

Circadian rhythm is a 24-hour cycle of behavioral and physiological changes. Disrupted sleep-wake patterns and circadian dysfunction are common in patients of Alzheimer Disease (AD) and are closely related with neuroinflammation. However, it is not well known how circadian rhythm of immune cells is altered during the progress of AD. Previously, we found presenilin 2 (Psen2) N141I mutation, one of familial AD (FAD) risk genes, induces hyperimmunity through the epigenetic repression of REV-ERBα expression in microglia and bone marrow-derived macrophage (BMDM) cells. Here, we investigated whether repression of REV-ERBα is associated with dysfunction of immune cell-endogenous or central circadian rhythm by analyses of clock genes expression and cytokine secretion, bioluminescence recording of rhythmic PER2::LUC expression, and monitoring of animal behavioral rhythm. Psen2 N141I mutation down-regulated REV-ERBα and induced selective over-production of IL-6 (a well-known clock-dependent cytokine) following the treatment of toll-like receptor (TLR) ligands in microglia, astrocytes, and BMDM. Psen2 N141I mutation also lowered amplitude of intrinsic daily oscillation in these immune cells representatives of brain and periphery. Of interest, however, the period of daily rhythm remained intact in immune cells. Furthermore, analyses of the central clock and animal behavioral rhythms revealed that central clock remained normal without down-regulation of REV-ERBα. These results suggest that Psen2 N141I mutation induces hyperimmunity mainly through the suppression of REV-ERBα in immune cells, which have lowered amplitude but normal period of rhythmic oscillation. Furthermore, our data reveal that central circadian clock is not affected by Psen2 N141I mutation.

OBJECTIVE: Sexual dysfunction is highly prevalent in both untreated and treated patients with schizophrenia. Sexual dysfunction is a major cause of poor quality of life, negative attitude to therapy and treatment non-compliance. We thereby conducted this study to better understand the predictors of subjective sexual dysfunction. METHODS: The subjects consisted of 83 patients (46 men; 37 women) who participated in an open label study on switching antipsychotics to olanzapine. All subjects met the Tenth Revision of International Classification of Diseases diagnostic criteria for schizophrenia. To better understand the predictors of subjective sexual dysfunction, we used the Liverpool University Neuroleptic Side-effect Rating scale (LUNSERS), a comprehensive self-rating instrument for assessing and quantifying the subjective adverse events during antipsychotic treatment. All patients were taking antipsychotics at the initiation of the study and were assessed using LUNSERS, the Simpson-Angus Scale (SAS), the Barnes Akathisia Rating scale (BARS), Abnormal Involuntary Movement Scale (AIMS), Clinical Global Impression (CGI), and the Positive and Negative Syndrome Scale (PANSS). They were also checked for their serum prolactin levels and vital signs before and after a 6-week treatment with olanzapine. In order to identify the cross-sectional and longitudinal predictors of LUNSERS hormonal side effect, we carried out multiple regression analyses. RESULTS: Prolactin levels, LUNSERS hormonal side effect, CGI, PANSS, SAS, AIMS, and BARS decreased after a 6-week treatment with olanzapine. At initial evaluation, cross-sectional predictors of LUNSERS hormonal side effect were red herring and allergic reaction subscale, but after the 6-week treatment with olanzapine, none of the variables were found to significantly predict LUNSERS hormonal side effect. Longitudinal predictors of LUNSERS hormonal side effect were LUNSERS extrapyramidal system side effect and prolactin levels. CONCLUSION: These findings suggested relationships among prolactin, extrapyramidal symptom, motor function and sexual dysfunction. After switching to olanzapine, sexual function of the patients improved subjectively. More studies are warranted as these results have significant implications for quality of life and treatment adherence.
Antipsychotic Agents ; Benzodiazepines ; Dyskinesias ; Humans ; Hypersensitivity ; International Classification of Diseases ; Phenothiazines ; Prolactin ; Psychomotor Agitation ; Quality of Life ; Schizophrenia ; Vital Signs

Sepsis is one of the significant causes of morbidity and mortality. The burden caused by sepsis has continued to increase in recent years in the Korea, highlighting the urgent need for the implementation of strategies to improve sepsis treatment outcomes. We therefore designed a web-based sepsis registry system (“Korean Registry for Improving Sepsis Survival” [KISS]) protocol to be used in hospitals in the Korea for evaluation of the epidemiology and clinical characteristics of patients with sepsis, via an analysis of outcome predictors. The inclusion criteria of this registry are as follows: adult patients ≥18 years admitted to the participating hospitals who are diagnosed with sepsis or septic shock. Demographic and clinical information data of the patients will be collected from hospital medical records and will be recorded in a case report form, which will be entered into a web-based data management system. The analysis of the collected data will be performed as follows: (1) epidemiological and clinical characteristics of sepsis and septic shock, (2) application of sepsis bundles and antibiotic stewardship, and (3) audit and feedback. In conclusion, we aim to build the comprehensive web-based sepsis registry in the Korea through a nation-wide network of participating hospitals. Information collected and analyzed through the KISS can be used for further improvements in the clinical management of sepsis. Furthermore, the KISS will facilitate research leading to the formulation of public health policies regarding sepsis bundle and antibiotic stewardship strategies in the Korea.

During the 2019 domestic measles outbreak in Korea, measles occurred in healthcare workers with two doses of the measles, mumps and rubella vaccine, and the strict application of the Occupational Safety and Health Act required medical institutions to identify healthcare workers' immunity to measles and vaccinate the susceptible pockets. In response to the frontline medical institutions' request to review the measles recommendations and guidelines, the Korean Society of Infectious Diseases held a roundtable discussion on the causes of measles outbreak, timing of vaccinations, antibody tests, and booster vaccinations for healthcare workers, and financial support from the government and municipality as well as response strategies against the outbreak in healthcare settings. In Korea, the seroprevalence of measles is decreasing in the vaccine-induced immunity group during the maintenance of measles elimination over several years. The susceptible group against measles is in their 20s and 30s, and this may be because of waning immunity rather than nonresponse considering Korea's vaccine policy. The risk of measles nosocomial infection from community increases as these susceptible pockets actively engage in medical institutions.Thus, data on the immunity of low seroprevalence group in Korea are needed, further discussion is needed on the booster vaccination based on the data. Especially, antibody testing and vaccination in healthcare workers may be necessary to prevent the spread of measles in medical insutitutions, and further discussion is needed regarding specific testing methods, and the timing and frequency of test and vaccination.

During the 2019 domestic measles outbreak in Korea, measles occurred in healthcare workers with two doses of the measles, mumps and rubella vaccine, and the strict application of the Occupational Safety and Health Act required medical institutions to identify healthcare workers' immunity to measles and vaccinate the susceptible pockets. In response to the frontline medical institutions' request to review the measles recommendations and guidelines, the Korean Society of Infectious Diseases held a roundtable discussion on the causes of measles outbreak, timing of vaccinations, antibody tests, and booster vaccinations for healthcare workers, and financial support from the government and municipality as well as response strategies against the outbreak in healthcare settings. In Korea, the seroprevalence of measles is decreasing in the vaccine-induced immunity group during the maintenance of measles elimination over several years. The susceptible group against measles is in their 20s and 30s, and this may be because of waning immunity rather than nonresponse considering Korea's vaccine policy. The risk of measles nosocomial infection from community increases as these susceptible pockets actively engage in medical institutions.Thus, data on the immunity of low seroprevalence group in Korea are needed, further discussion is needed on the booster vaccination based on the data. Especially, antibody testing and vaccination in healthcare workers may be necessary to prevent the spread of measles in medical insutitutions, and further discussion is needed regarding specific testing methods, and the timing and frequency of test and vaccination.