Pathogenic microbes secrete various enzymes with lipolytic activities to facilitate their survival within the host. Lipolytic enzymes include extracellular lipases and phospholipases, and several lines of evidence have suggested that these enzymes contribute to the virulence of pathogenic fungi. Candida albicans and Cryptococcus neoformans are the most commonly isolated human fungal pathogens, and several biochemical and molecular approaches have identified their extracellular lipolytic enzymes. The role of lipases and phospholipases in the virulence of C. albicans has been extensively studied, and these enzymes have been shown to contribute to C. albicans morphological transition, colonization, cytotoxicity, and penetration to the host. While not much is known about the lipases in C. neoformans, the roles of phospholipases in the dissemination of fungal cells in the host and in signaling pathways have been described. Lipolytic enzymes may also influence the survival of the lipophilic cutaneous pathogenic yeast Malassezia species within the host, and an unusually high number of lipase-coding genes may complement the lipid dependency of this fungus. This review briefly describes the current understanding of the lipolytic enzymes in major human fungal pathogens, namely C. albicans, C. neoformans, and Malassezia spp.
Candida albicans ; Colon ; Complement System Proteins ; Cryptococcus neoformans ; Dependency (Psychology) ; Fungi ; Humans ; Lipase ; Malassezia ; Phospholipases ; Yeasts

OBJECTIVES: A growing body of evidence has suggested that morphologic changes in cerebellum may be implicated with pathophysiology of major depressive disorder (MDD). The aim of this study is to investigate a difference in the volume and cortical thickness of the specific region of cerebellum between patients with MDD and healthy controls (HC). METHODS: A total of 127 patients with MDD and 105 HC participated in this study and underwent T1-weighted structural magnetic resonance imaging. We analyzed volume and cortical thickness of each twelve cerebellum regions divided by left and right and the volume and cortical thickness of the whole cerebellum from T1-weigted image of participants. One-way analysis of covariance was used to investigate the volume and cortical thickness difference of total and specific regions between two groups adjusting for age, gender, medication, and total intracranial cavity volume. RESULTS: We found that the patients with MDD had significantly greater volume in the left cerebellum lobule III region [false discovery rate (FDR)-corrected p = 0.034] compared to HC. Also, our findings indicate that cortical thickness of left lobule VIIB (FDR-corrected p = 0.032) and lobule VIIIB (FDR-corrected p = 0.032) are significantly thinner in the patients with MDD compared with the HC. No significant volume and cortical thickness differences were observed in other sub-regions of the cerebellum. The volumes and cortical thickness of whole cerebellum between patients with MDD and HC did not differ significantly. CONCLUSIONS: We observed the region-specific volume and cortical thickness difference in cerebellum between the patients with MDD and HC. The results of our study implicate that the information about structural alterations in cerebellum with further replicative studies might provide a stepping stone toward a specific marker to diagnose MDD.
Cerebellum* ; Depressive Disorder, Major* ; Humans ; Magnetic Resonance Imaging

Mitochondrial protein Nfu1 plays an important role in the assembly of mitochondrial Fe-S clusters and intracellular iron homeostasis in the model yeast Saccharomyces cerevisiae. In this study, we identified the Nfu1 ortholog in the human fungal pathogen Cryptococcus neoformans. Our data showed that C. neoformans Nfu1 localized in the mitochondria and influenced homeostasis of essential metals such as iron, copper and manganese. Marked growth defects were observed in the mutant lacking NFU1, which suggests a critical role of Nfu1 in Fe-S cluster biosynthesis and intracellular metal homeostasis in C. neoformans.
Copper ; Cryptococcus neoformans* ; Homeostasis* ; Humans ; Iron ; Manganese ; Metals* ; Mitochondria ; Mitochondrial Proteins* ; Saccharomyces cerevisiae ; Yeasts

OBJECTIVES: To determine the relationship between the Alu insertion/deletion (I/D) polymorphism in the tissue-type plasminogen activator (tPA) gene and the clinical outcome of mirtazapine treatment in Korean major depressive disorder (MDD) patients. METHODS: We enrolled 422 patients in this study. Symptoms were evaluated using the 21-item Hamilton Depression Rating (HAMD-21) Scale. After 1, 2, 4, and 8 weeks of mirtazapine treatment, the association between the Alu I/D polymorphism in the tPA gene and remission/response outcomes were evaluated. RESULTS: The proportion of I/I homozygotes in responders was higher than that in non-responders, whereas the proportion of D/D homozygotes in responders was lower than that in non-responders at 8 weeks of treatment (p = 0.032, OR = 1.57). The percentage decline of HAMD-21 scores in I allele carriers was larger than that of D/D homozygotes at 2 and 8 weeks of treatment (p = 0.035 and 0.007, respectively). I allele carriers were associated with remission at 8 weeks of treatment (p = 0.047, OR = 2.2). CONCLUSIONS: These results show that treatment response and remission to mirtazapine were associated with the Alu I/D polymorphism of the tPA gene. This suggests the Alu I/D polymorphism may be a potential genetic marker for the prediction of therapeutic response to mirtazapine treatment in patients with MDD.
Alleles ; Depression* ; Depressive Disorder, Major ; Genetic Markers ; Homozygote ; Humans ; Polymorphism, Genetic ; Tissue Plasminogen Activator*

OBJECTIVES: Local gyrification reflects the early neural development of cortical connectivity, and is regarded as a potential neural endophenotype in psychiatric disorders. Several studies have suggested altered local gyrification in patients with bipolar I disorder (BD-I). The purpose of the present study was to investigate the alterations in the cortical gyrification of whole brain cortices in patients with BD-I. METHODS: Twenty-two patients with BD-I and age and sex-matched 22 healthy controls (HC) were included in this study. All participants underwent T1-weighted structural magnetic resonance imaging (MRI). The local gyrification index (LGI) of 66 cortical regions were analyzed using the FreeSurfer (Athinoula A. Martinos Center for Biomedical Imaging). One-way analysis of covariance (ANCOVA) was used to analyze the difference of LGI values between two groups adjusting for age and sex as covariates. RESULTS: The patients with BD-I showed significant hypogyria in the left pars opercularis (uncorrected-p = 0.049), the left rostral anterior cingulate gyrus (uncorrected-p = 0.012), the left caudal anterior cingulate gyrus (uncorrected-p = 0.033). However, these findings were not significant after applying the multiple comparison correction. Severity or duration of illness were not significantly correlated with LGI in the patients with BD-I. CONCLUSIONS: Our results of lower LGI in the anterior cingulate cortex and the ventrolateral prefrontal cortex in the BD-I group implicate that altered cortical gyrification in neural circuits involved in emotion-processing may contribute to pathophysiology of BD-I.
Bipolar Disorder ; Brain ; Broca Area ; Endophenotypes ; Gyrus Cinguli ; Humans ; Magnetic Resonance Imaging ; Prefrontal Cortex

Objective: Early trauma (ET) is widely recognized as a contributing factor to the development of panic disorder (PD) in patients. However, there is a dearth of research on the specific volumes of hippocampal subregions and their laterality with respect to ET and PD. Methods: A total of 30 subjects with PD and 30 age- and sex-matched healthy controls (HCs) were included in this study. All the subjects were evaluated by 3T-magnetic resonance imaging. FreeSurfer version 6.0 was used for volumetric analysis of the hippocampal subregions and their laterality. A shortened version of the Early Trauma Inventory Self Report (ETISR) as well as Anxiety Sensitivity Inventory-Revised (ASI-R), and Panic Disorder Severity Scale were utilized for analysis. Results: Multivariate analysis of variance showed that the volume of the right hippocampal tail and laterality indices (LIs) of the hippocampal body and tail were significantly larger in subjects with PD relative to HCs. The significance of the observations remained unchanged after multivariate analysis of covariance, controlling for age, sex, years of education, medication, depressive symptoms, and intracranial volume as covariates. The LIs of the hippocampal tails that showed a significant correlation to ETISR emotional and physical subscales were also associated with ASI-R for cardiovascular symptoms in PD. Conclusion Our study displayed an increased rightward lateralization of the hippocampal tails in subjects with PD compared with HCs. This alteration in the brain, which was associated with early emotional and physical trauma, would negatively affect anxiety sensitivity to cardiovascular symptoms in subjects with PD.

Objective: Although neural correlates of sub-clinical agoraphobia (AG) symptoms have been previously suggested, only a few studies evaluating structural changes of the brain have been conducted in agoraphobic patients with panic disorder (PD). We investigated and compared white matter (WM) micro-structural alterations between PD patients with AG (PD ＋ AG) and those without AG (PD − AG). Methods: Our study included 56 female PD patients, of which 25 were diagnosed with AG and 31 were diagnosed without AG. Diffusion tensor imaging was performed to investigate micro-structural changes in the WM tracts related to fronto-temporo-occipital areas (uncinate fasciculus, cingulum bundle, inferior longitudinal/fronto-occipital fasciculus, fornix column and body, and fornix/stria terminalis). All participants were subjected to the Anxiety Sensitivity Inventory-Revised (ASI-R), Beck Depression Inventory-II (BDI-II), and Albany Panic and Phobia questionnaires. Results: The fractional anisotropy values of the right uncinate fasciculus in PD ＋ AG were significantly lower than that of PD − AG and showed significant correlations with BDI-II and ASI-R total scores. Mean diffusivity and radial diffusivity values of the right uncinate fasciculus were significantly higher in PD ＋ AG as compared to PD − AG. Conclusion Our findings suggest that the uncinate fasciculus may be associated with AG symptoms in PD, possibly through demyelination. Our findings may contribute to the neurobiological evidence regarding the association between AG and WM structural changes in PD.

A 74-year-old man who had been receiving warfarin for atrial fibrillation, underwent emergency thrombectomy. A central venous catheter (CVC) was inserted via the left subclavian vein, and heparin was administered to prevent preoperative and postoperative thrombotic events. After an uneventful thrombectomy, the patient was transferred to the intensive care unit (ICU). On the second postoperative day, the patient developed syncope and his blood pressure and oxygen saturation decreased. A computed tomography (CT) revealed a huge hematoma under the pectoralis major muscle. The patient was then treated with continuous renal replacement therapy and mechanical ventilation for multiorgan dysfunction syndrome, which developed due to hemorrhagic shock in the ICU. These findings suggest that when a CVC is inserted in patients requiring anticoagulant therapy, the possible risk of excessive bleeding must be carefully considered. Further, choosing a proper insertion site and performing an ultrasound-guided aspiration may be helpful in preventing these complications.
Aged ; Anticoagulants ; Atrial Fibrillation ; Blood Pressure ; Catheters* ; Central Venous Catheters ; Emergencies ; Hematoma* ; Hemorrhage ; Heparin ; Humans ; Intensive Care Units ; Oxygen ; Renal Replacement Therapy ; Respiration, Artificial ; Shock, Hemorrhagic* ; Subclavian Vein ; Syncope ; Thrombectomy ; Warfarin

BACKGROUND: Desflurane has lower solubility and shows a more rapid induction and recovery than sevoflurane, although it often induces increased cardiovascular response, emergence delirium, and respiratory complications. The change of anesthetic agent from sevoflurane to desflurane after induction may provide a smooth induction and rapid emergence. The aim of this study was to evaluate the effect of changing sevoflurane to desflurane after induction on the cardiovascular response, emergence delirium, and recovery characteristics during pediatric strabismus surgery. METHODS: For the study, 135 children scheduled for strabismus surgery were randomly divided into three groups: the S group (n = 45) and D group (n = 45) received sevoflurane or desflurane, respectively, for induction and maintenance, while the C group (n = 45) received sevoflurane for induction and desflurane for maintenance. Cardiovascular responses, pediatric anesthesia emergence delirium (PAED) scale scores, post-anesthesia care unit (PACU) length of stay, and the incidence of postoperative complications were compared between groups. RESULTS: The blood pressure of the D group was significantly different from that of the S and C groups (P < 0.05). The time to extubation and first crying were significantly longer in the S group (P < 0.001). There were no significant differences in PAED score, PACU length of stay, and the incidence of postoperative complications, except for cough, among the three groups. CONCLUSIONS: The change of desflurane after sevoflurane induction in pediatric strabismus surgery provided rapid emergence compared with sevoflurane, and attenuated cardiovascular responses and lesser respiratory complications as compared to desflurane. The emergence delirium was not influenced by either inhalational anesthetic.
Anesthesia* ; Blood Pressure ; Child ; Cough ; Crying ; Delirium* ; Humans ; Incidence ; Length of Stay ; Postoperative Complications ; Solubility ; Strabismus*

Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder characterized by fever, pancytopenia, hyperferritinemia, and phagocytosis of hematopoietic cells in bone marrow, liver, or lymph nodes. HLH can occur during the course of systemic lupus erythematosus (SLE), but can also be a presenting manifestation. Because development of pancytopenia occurs in less than 10 percent of SLE cases, investigation for HLH is necessary when otherwise unexplained pancytopenia persists despite adequate treatment. We experienced three cases of secondary HLH associated with SLE. Among the three patients, two patients developed HLH during the clinical course of SLE. The other patient who presented with pancytopenia was first diagnosed with HLH, and later with SLE. In her case, HLH turned out to be a presenting manifestation of SLE. We report on three successfully treated cases, and discuss the prevalence, characteristics, treatments, and prognosis of secondary HLH associated with SLE.
Bone Marrow ; Fever ; Humans ; Liver ; Lupus Erythematosus, Systemic ; Lymph Nodes ; Lymphohistiocytosis, Hemophagocytic* ; Pancytopenia ; Phagocytosis ; Prevalence ; Prognosis