Multiple roads lead to Rome: unique morphology and chemistry of endospores, exospores, myxospores, cysts and akinetes in bacteria.

The production of specialized resting cells is a remarkable survival strategy developed by many organisms to withstand unfavourable environmental factors such as nutrient depletion or other changes in abiotic and/or biotic conditions. Five bacterial taxa are recognized to form specialized resting cells: Firmicutes, forming endospores; Actinobacteria, forming exospores; Cyanobacteria, forming akinetes; the δ-Proteobacterial order Myxococcales, forming myxospores; and Azotobacteraceae, forming cysts. All these specialized resting cells are characterized by low-to-absent metabolic activity and higher resistance to environmental stress (desiccation, heat, starvation, etc.) when compared to vegetative cells. Given their similarity in function, we tested the potential existence of a universal morpho-chemical marker for identifying these specialized resting cells. After the production of endospores, exospores, akinetes and cysts in model organisms, we performed the first cross-species morphological and chemical comparison of bacterial sporulation. Cryo-electron microscopy of vitreous sections (CEMOVIS) was used to describe near-native morphology of the resting cells in comparison to the morphology of their respective vegetative cells. Resting cells shared a thicker cell envelope as their only common morphological feature. The chemical composition of the different specialized resting cells at the single-cell level was investigated using confocal Raman microspectroscopy. Our results show that the different specialized cells do not share a common chemical signature, but rather each group has a unique signature with a variable conservation of the signature of the vegetative cells. Additionally, we present the validation of Raman signatures associated with calcium dipicolinic acid (CaDPA) and their variation across individual cells to develop specific sorting thresholds for the isolation of endospores. This provides a proof of concept of the feasibility of isolating bacterial spores using a Raman-activated cell-sorting platform. This cross-species comparison and the current knowledge of genetic pathways inducing the formation of the resting cells highlights the complexity of this convergent evolutionary strategy promoting bacterial survival.

Long-term benefits of mindfulness on white matter tracts underlying the cortical midline structures in panic disorder: A 2-year longitudinal study.

AIMS: We aimed to examine the long-term benefits of mindfulness-based cognitive therapy (MBCT) on white matter plasticity in the cortical midline structures (CMS) for a period of 2 years in patients with panic disorder and the relationships between white matter changes in the CMS and severity of state and trait symptoms. METHODS: Seventy-one participants were enrolled and underwent diffusion tensor imaging at baseline and after 2 years (26 who received MBCT as an adjunct to pharmacotherapy [MBCT+PT], 20 treated with pharmacotherapy alone [PT-alone], and 25 healthy controls [HCs]). The severity of symptoms and fractional anisotropy (FA) in white matter regions underlying the CMS were assessed at baseline and 2-year follow-up. RESULTS: The MBCT+PT group showed better outcomes after 2 years than the PT-alone group. The groups showed different FA changes: the MBCT+PT group showed decreased FA in the left anterior cingulate cortex (ACC); the PT-alone group showed increased FA in the bilateral dorsomedial prefrontal cortex, posterior cingulate cortex (PCC), and precuneus. Decreased white matter FA in the ACC, PCC, and precuneus was associated with improvements in the severity of state and trait symptoms in patients with panic disorder. CONCLUSION: Alleviation of excessive white matter connectivity in the CMS after MBCT leads to improvements in clinical symptoms and trait vulnerability in patients with panic disorder. Our study provides new evidence for the long-term benefits of MBCT on white matter plasticity and its clinical applicability as a robust treatment for panic disorder.

Suicide risk within 1 year of dementia diagnosis in older adults: a nationwide retrospective cohort study.

BACKGROUND: Although severe dementia could protect against suicide death by decreasing a person's capacity to implement a suicide plan, patients with early dementia may have better cognition, giving them more sustained insight into their disease and better enabling them to carry out a suicide plan. This study investigated suicide risk in older adults within 1 year of receiving a diagnosis of dementia. METHODS: This study used National Health Insurance Service Senior Cohort data and included 36 541 older adults with newly diagnosed dementia (a Mini-Mental State Examination score ≤ 26 and a Clinical Dementia Rating score ≥ 1 or a Global Deterioration Scale score ≥ 3), including Alzheimer disease, vascular dementia and other/unspecified dementia, from 2004 to 2012. We selected older adults without dementia through 1:1 propensity-score matching using sex, age, comorbidities and index year, with follow-up throughout 2013. We estimated adjusted hazard ratios (AHRs) of suicide deaths within 1 year after diagnosis using a time-dependent Cox proportional hazards model. RESULTS: We verified 46 suicide deaths during the first year after a dementia diagnosis. Older adults with dementia had an increased risk of suicide death compared to those without dementia (AHR 2.57; 95% confidence interval [CI] 1.49-4.44). Older adults with Alzheimer disease (AHR 2.50; 95% CI 1.41-4.44) or other/unspecified dementia (AHR 4.32; 95% CI 2.04-9.15) had an increased risk of suicide death compared to those without dementia. Patients with dementia but without other mental disorders (AHR 1.96; 95% CI 1.02-3.77) and patients with dementia and other mental disorders (AHR 3.22; 95% CI 1.78-5.83) had an increased risk of suicide death compared to patients without dementia. Patients with dementia and schizophrenia (AHR 8.73; 95% CI 2.57-29.71), mood disorders (AHR 2.84; 95% CI 1.23-6.53) or anxiety or somatoform disorders (AHR 3.53; 95% CI 1.73-7.21), respectively, had an increased risk of suicide death compared to patients with those conditions but without dementia. LIMITATIONS: This study examined only elderly patients in South Korea, a population with a substantially higher suicide rate than the global population. Caution must be exercised when generalizing the results to populations with dissimilar backgrounds. CONCLUSION: Patients with dementia had an increased risk of suicide death within 1 year after diagnosis compared to those without dementia.

White Matter-Based Structural Brain Network of Anxiety.

Anxiety disorders are characterized by excessive fear and anxiety and related behavioral disturbances. Because diffusion tensor imaging is sensitive to detect subtle pathology of the brain, it has been used to characterize differences in white matter microstructure for a broad spectrum of psychiatric disorders. The neurobiological underpinnings of a trait anxiety seem to be associated with the uncinate fasciculus, a major pathway between the amygdala and orbitofrontal cortex. Apparent WM micro-alterations in patients with panic disorder are present in diverse and widespread regions, although alterations vary in terms of clinical symptom severity and comorbidities. Social anxiety disorder is associated with structural dysconnectivity in a fronto-limbic network consistent with reduced fractional anisotropy values in uncinate fasciculus and inferior longitudinal fasciculus. The pathogenesis of obsessive-compulsive disorder may include abnormal findings in not only the fronto-striato-thalamic circuit but also the posterior and temporal regions of forceps major and cingulum bundle. Studies of white matter status in anxiety revealed overlapping patterns of front-cortical and fronto-limbic changes with uncinate fasciculus and cingulum alterations a frequent component.

Hazard Ratio of Smoking on Lung Cancer in Korea According to Histological Type and Gender.

PURPOSE: Using nationwide cancer incidence data, we examined whether the strength of the association of cigarette smoking with lung cancer risk differs according to major histological type and gender, taking account of other risk factors in the Korean population. METHODS: The study population derived from government employees and teachers aged 20 years and over who participated in a national health examination program in 1998 or 1999. Total study subjects were 1,357,447. After excluding 1556 subjects who were treated with lung cancer during 1998-2000, we restricted our analysis to 1,355,891 cases. We followed up those 1,355,891 subjects who were cancer-free at baseline until December 31, 2010. The incident cancer cases were identified from the Korea Central Cancer Registry, which is a nationwide hospital-based cancer registry system that includes 94 % of the university hospitals and 96 % of the resident training hospitals of the country. RESULTS: A higher risk for having ever smoked was observed for squamous-cell and small-cell carcinoma in both men and women. Heavy and long-term smokers were at higher risk for these carcinomas. Significant associations with quantity and duration-related factors were observed mainly among men. These findings indicate that smoking is closely related to the risk of squamous-cell and small-cell carcinoma among women as well as men. However, the magnitude of smoking-related lung cancer risk is likely to differ between men and women. CONCLUSION: The hazard ratios for all types of lung cancer were significantly higher in male current smokers than in male never smokers. In case of women, the hazard ratios for adenocarcinoma were not different between current smokers and never smokers. The hazard ratios we found, however, were lower than those reported in Western countries and in Korea, but consistent with those reported in North-eastern Asian countries.

Interdimensional universality of dynamic interfaces.

Despite the complexity and diversity of nature, there exists universality in the form of critical scaling laws among various dissimilar systems and processes such as stock markets, earthquakes, crackling noise, lung inflation and vortices in superconductors. This universality is mainly independent of the microscopic details, depending only on the symmetry and dimension of the system. Exploring how universality is affected by the system dimensions is an important unresolved problem. Here we demonstrate experimentally that universality persists even at a dimensionality crossover in ferromagnetic nanowires. As the wire width decreases, the magnetic domain wall dynamics changes from elastic creep in two dimensions to a particle-like stochastic behaviour in one dimension. Applying finite-size scaling, we find that all our experimental data in one and two dimensions (including the crossover regime) collapse onto a single curve, signalling universality at the criticality transition. The crossover to the one-dimensional regime occurs at a few hundred nanometres, corresponding to the integration scale for modern nanodevices.

Association of alcohol drinking with verbal and visuospatial memory impairment in older adults: Clinical Research Center for Dementia of South Korea (CREDOS) study.

BACKGROUND: The study's aim was to examine the association of alcohol consumption with verbal and visuospatial memory impairment in older people. METHODS: Participants were 1,572, aged ≥60 years, in the hospital-based registry of the Clinical Research Center for Dementia of South Korea (CREDOS). Moderate drinking was defined as no more than seven drinks per week and three drinks per day. Memory impairment was defined as performance with more than 1 standard deviation below the mean value on the Seoul Verbal Learning Test and Rey Complex Figure Test. RESULTS: Those who consumed alcohol moderately, compared with abstainers, had a lower odds of verbal memory impairment (Odds Ratio [OR] = 0.64; 95% Confidence Interval [CI]: 0.46-0.87), adjusting for covariates. Visuospatial memory, however, was not significantly associated with alcohol consumption. CONCLUSIONS: Moderate alcohol drinking is associated with a reduced likelihood of verbal memory impairment among older people attending memory clinics.

Effects of a multidomain lifestyle modification on cognitive function in older adults: an eighteen-month community-based cluster randomized controlled trial.

BACKGROUND: A healthy lifestyle may protect against cognitive decline. We examined outcomes in elderly individuals after 18 months of a five-group intervention program consisting of various modalities to prevent cognitive decline. METHODS: We conducted a cluster randomized controlled trial assessing 460 community-dwelling individuals aged 60 years and older in a geriatric community mental health center in Suwon, Republic of Korea, between 2008 and 2010. We developed an intervention program based on the principles of contingency management, which could be delivered by ordinary primary health workers. Group A (n = 81) received standard care services. Group B (n = 80) received bimonthly (once every 2 months) telephonic care management. Group C (n = 111) received monthly telephonic care management and educational materials similar to those in group B. Group D (n = 93) received bimonthly health worker-initiated visits and counseling. Group E (n = 94) received bimonthly health worker-initiated visits, counseling, and rewards for adherence to the program. RESULTS: The primary outcome was the change in Mini-Mental State Examination (MMSE) scores from baseline to the final follow-up visit at 18 months. Group E showed superior cognitive function to group A (adjusted coefficient ß = 0.99, p = 0.044), with participation in cognitive activities being the most important determining factor among several health behaviors (adjusted coefficient ß = 1.04, p < 0.01). CONCLUSIONS: Engaging in cognitive activities, in combination with positive health behaviors, may be most beneficial in preserving cognitive abilities in community-dwelling older adults.

Neural Correlates of Trait Impulsivity among Adult Healthy Individuals.

Objective: : Impulsivity can be observed in individuals with or without mental illness. The discovery of neural correlates responsible for trait impulsivity can therefore help to understand the severity of psychiatric symptoms, personality characteristics and social adjustment. In this study, we aimed to identify the gray matter substrates of trait impulsivity in healthy individuals. Methods: : Seventy-five healthy individuals were enrolled. At baseline, trait impulsivity was assessed using the Barratt Impulsiveness Scale (BIS) and all participants underwent T1-weighted magnetic resonance imaging scan. Beck Anxiety Inventory (BAI), World Health Organization Quality of Life (WHOQOL-BREF) and Connor-Davidson Resilience Scale (CD-RISC) were also assessed. Mean cortical thickness (CT) and the local gyrification index (LGI) were calculated to perform whole-brain vertex-wise correlation analysis, which were performed to investigate the relationship between BIS scores and CT or LGI in each brain region. We also revealed the relationship between brain regions and psychological measurements. Results: : Total BIS scores were significantly and negatively correlated with mean CT values in the left lateral occipital cortex (OC) and LGIs in the inferior frontal gyrus (IFG). Correlation analyses revealed that the lateral OC's mean CT values were negatively correlated with BAI scores and positively correlated with WHOQOL-BREF scores, while LGI in the IFG was positively correlated with CD-RISC scores. Conclusion: : Our study showed that trait impulsivity might be associated with the lateral OC and IFG in healthy individuals. Understanding the neural correlates of trait impulsivity could provide ways to expect high impulsivity, anxiety, and poor resilience in healthy adults.

Survival of Alzheimer's disease patients in Korea.

BACKGROUND/AIMS: The natural history of Alzheimer's disease (AD) has rarely been studied in the Korean population. Our study on survival analyses in Korean AD patients potentially provides a basis for cross-cultural comparisons. METHODS: We studied 724 consecutive patients from a memory disorder clinic in a tertiary hospital in Seoul, who were diagnosed as having AD between April 1995 and December 2005. Deaths were identified by the Statistics Korea database. The Kaplan-Meier method was used for survival analysis, and a Cox proportional hazard model was used to assess factors related to patient survival. RESULTS: The overall median survival from the onset of first symptoms and from the time of diagnosis was 12.6 years (95% confidence interval 11.7-13.4) and 9.3 years (95% confidence interval 8.7-9.9), respectively. The age of onset, male gender, history of diabetes mellitus, lower Mini-Mental State Examination score, and higher Clinical Dementia Rating score were negatively associated with survival. There was a reversal of risk of AD between early-onset and later-onset AD, 9.1 years after onset. CONCLUSIONS: The results of our study show a different pattern of survival compared to those studies carried out with western AD populations. Mortality risk of early-onset AD varied depending on the duration of follow-up.

Serotonergic genes (5-HTT and HTR1A) and separation life events: gene-by-environment interaction for panic disorder.

BACKGROUND: The polymorphisms of serotonergic genes (5-HTTLPR and HTR1A rs6295) and separation life events have been studied to find an association with panic disorder, respectively. However, there are no studies that have yet evaluated the interaction effect between serotonergic genes and separation life events for panic disorder. METHODS: For this study, 194 panic disorder patients and 172 healthy controls were included for genotyping and environmental factor analysis. Separation life events were assessed using the Stressful Life Events Scale and clinical interviews. To evaluate the potential endophenotypes of panic disorder, the Anxiety Sensitivity Index-revised (ASI-R), harm avoidance in the Temperament and Character Inventory (HA), and neuroticism in the Eysenck Personality Questionnaire (neuroticism) scales were administered. RESULTS: For 5-HTTLPR and HTR1A rs6295, there was no significant main effect of each genotype on panic disorder alone. However, the number of separation life events and their interaction with 5-HTTLPR showed a statistically significant effect on panic disorder. In addition, the interaction between 5-HTTLPR and the number of separation life events significantly affected the HA for potential endophenotypes. CONCLUSION: This study could suggest the effect of the interaction between 5-HTTLPR and separation life events on panic disorder and its potential endophenotype.

Impact of Intolerance of Uncertainty on Brain Structural Changes in Panic Disorder.

OBJECTIVE: This study investigated the impact of intolerance of uncertainty (IU) on structural changes in the brain and symptom severity in patients with panic disorder. METHODS: This study included 90 participants diagnosed with panic disorder. The IU Scale, Panic Disorder Severity Scale (PDSS), Beck Depression Inventory-II (BDI-II), Penn State Worry Questionnaire (PSWQ), Self-Forgiveness Scale (SFS), and Short Form 36 Health Survey (SF) were used. A voxel-wise correlation analysis was conducted to investigate the structural differences in the gray matter. RESULTS: As IU increased, the cortical thickness of the right lingual gyrus decreased significantly, while the gray matter volume of the right pars triangularis increased. The cortical thickness of the right lingual gyrus showed a significant negative correlation with the BDI-II score and a positive correlation with the SFS. Additionally, the gray matter volume of the right pars triangularis was positively correlated with the PDSS, PSWQ, and BDI-II scores and negatively correlated with the mental health domain of the SF. CONCLUSION: According to our findings, elevated IU in participants with panic disorder was associated with cortical thinning in the lingual gyrus and increased gray matter volume in the pars triangularis. These structural alterations may also have an impact on perceived quality of life, as well as high levels of depression and anxiety.

Identification of inulin-responsive bacteria in the gut microbiota via multi-modal activity-based sorting.

Prebiotics are defined as non-digestible dietary components that promote the growth of beneficial gut microorganisms. In many cases, however, this capability is not systematically evaluated. Here, we develop a methodology for determining prebiotic-responsive bacteria using the popular dietary supplement inulin. We first identify microbes with a capacity to bind inulin using mesoporous silica nanoparticles functionalized with inulin. 16S rRNA gene amplicon sequencing of sorted cells revealed that the ability to bind inulin was widespread in the microbiota. We further evaluate which taxa are metabolically stimulated by inulin and find that diverse taxa from the phyla Firmicutes and Actinobacteria respond to inulin, and several isolates of these taxa can degrade inulin. Incubation with another prebiotic, xylooligosaccharides (XOS), in contrast, shows a more robust bifidogenic effect. Interestingly, the Coriobacteriia Eggerthella lenta and Gordonibacter urolithinfaciens are indirectly stimulated by the inulin degradation process, expanding our knowledge of inulin-responsive bacteria.

Optofluidic particle manipulation in a liquid-core/liquid-cladding waveguide.

This paper describes a method for particle manipulation in a liquid-core/liquid-cladding optical waveguide system. Step-index and graded-index waveguides were modeled with consideration for, respectively, miscible and immiscible core and cladding fluids. The characteristic motions of four different particles with refractive indices of 1.59, 1.48, 1.37, and 1.22 were examined. The guided beam was assumed to be Gaussian in shape. Our results showed that high-refractive-index particles converged at the center of the core fluid due to a positive gradient force, whereas low-refractive-index particles converged at the flow periphery. The nonlinearity of the particle motion increased as the flow velocity and the guided beam waist decreased and the laser power and the particle size increased. The initial beam waist of the guided beam in the graded-index waveguide did not significantly affect the characteristics of the particle motion due to the effects of diffusion.

Behavior of double emulsions in a cross-type optical separation system.

The behavior of double emulsions in a cross-type optical particle separation system was studied for different combinations of refractive indices and different inner and outer layer radii. The radii and refractive indices of the double emulsions were easily adjusted by taking advantage of the coflowing geometry of a cross-type optical particle separation device. An analytical expression of the optical forces on a pair of concentric spheres was derived using the photon stream method in the ray optics regime. The predicted trajectories of the double emulsions by the optical force agreed well with the experimental data. This work has potential uses in cell separation by morphometry, drug delivery vehicle, and emulsion-based biomedical applications.

Safety and Effectiveness of Desvenlafaxine in Korean Patients with Major Depressive Disorder: A 6-month Postmarketing Surveillance Study.

Objective: Although the safety and efficacy of desvenlafaxine have been demonstrated, long-term evidence in Asians is lacking. We examined the safety and effectiveness of desvenlafaxine for up to 6 months in routine clinical practice in Korea. Methods: This multicenter, open-label, prospective observational study was conducted from February 2014 to February 2020 as a postmarketing surveillance study of desvenlafaxine (ClinicalTrials.gov identifier: NCT02548949). Adult patients with major depressive disorder (MDD) were observed from the initiation of treatment for 8 weeks (acute treatment phase) and then up to 6 months (continuation treatment phase) in a subsample. Safety was evaluated by incidence of adverse events (AE) and adverse drug reactions. Treatment response was assessed using the Clinical Global Impression- Improvement (CGI-I) scale. Results: We included 700 and 236 study subjects in the analysis of acute and continuation treatment phase, respectively. In acute treatment phase, AE incidence was 9.86%, with nausea being most common (2.00%). In continuation treatment phase, AE incidence was 2.97%, with tremor occurring most frequently. After acute treatment (n = 464), the treatment response rate according to the CGI-I score at week 8 was 28.9%. In long-term users (n = 213), the response rate at month 6 was 45.5%. During the study period, no clinically relevant changes in BP were found regardless of concomitant use of antihypertensive drugs. Conclusion: This study provides evidence on the safety and effectiveness of desvenlafaxine in adults with MDD, with a low incidence of AE, consistent AE profile with previous studies, and improved response after long-term treatment.

Universality classes of magnetic domain wall motion.

We examine magnetic domain wall motion in metallic nanowires Pt-Co-Pt. Regardless of whether the motion is driven by either magnetic fields or current, all experimental data fall onto a single universal curve in the creep regime, implying that both the motions belong to the same universality class. This result is in contrast to the report on magnetic semiconductor (Ga,Mn)As exhibiting two different universality classes. Our finding signals the possible existence of yet other universality classes which go beyond the present understanding of the statistical mechanics of driven interfaces.

Control of magnetic domain-wall polarization by means of angled Oersted field writing.

We propose a method to control the polarization of the magnetic domain walls (DWs) in ferromagnetic nanowires. Two neighboring DWs with antiparallel polarization alignment rather than parallel alignment are found to exhibit better stability with a helical magnetic structure that can be hardly be detangled. To achieve such an antiparallel alignment, two co-planar current lines with an angle to the nanowire are designed, from which the Oersted field creates a domain in between the current lines while keeping the polarization of the DWs beneath the current lines, as confirmed by a micromagnetic calculation for ferromagnetic nanowires with perpendicular magnetic anisotropy.

Anemia associated with depressive symptoms in mild cognitive impairment with severe white matter hyperintensities.

Depression with mild cognitive impairment (MCI) may be associated with a high risk of dementia. Likewise, anemia and subcortical ischemic changes might be associated with depression in the elderly individuals. We examined the relationship between anemia, subcortical ischemic changes, and depressive symptoms in 388 elderly patients with MCI (74.0% women, mean age = 71.8) who were evaluated at the Clinical Research Center for Dementia of South Korea. Blood samples were drawn from all consenting participants and depressive symptoms were assessed using the 15-item Geriatric Depression Scale (GDS-15). We also evaluated the severity of white matter hyperintensities (WMH) on brain using magnetic resonance imaging (MRI). After a multivariable adjustment, we found no significant differences in GDS-15 score between anemic and nonanemic groups (F = 3.0, P = .085) and among WMH level groups (F = 0.6, P = .574) independently. However, the interaction between anemia and the severity of WMH was significantly associated with depressive symptoms (analysis of covariance, F = 7.8, P < .001). In post hoc tests, a higher depressive symptom score was observed in anemic participants with severe WMH. Anemia with severe subcortical ischemic changes appears to be related to depressive symptoms in patients with MCI.

Optofluidic Raman-activated cell sorting for targeted genome retrieval or cultivation of microbial cells with specific functions.

Stable isotope labeling of microbial taxa of interest and their sorting provide an efficient and direct way to answer the question "who does what?" in complex microbial communities when coupled with fluorescence in situ hybridization or downstream 'omics' analyses. We have developed a platform for automated Raman-based sorting in which optical tweezers and microfluidics are used to sort individual cells of interest from microbial communities on the basis of their Raman spectra. This sorting of cells and their downstream DNA analysis, such as by mini-metagenomics or single-cell genomics, or cultivation permits a direct link to be made between the metabolic roles and the genomes of microbial cells within complex microbial communities, as well as targeted isolation of novel microbes with a specific physiology of interest. We describe a protocol from sample preparation through Raman-activated live cell sorting. Subsequent cultivation of sorted cells is described, whereas downstream DNA analysis involves well-established approaches with abundant methods available in the literature. Compared with manual sorting, this technique provides a substantially higher throughput (up to 500 cells per h). Furthermore, the platform has very high sorting accuracy (98.3 ± 1.7%) and is fully automated, thus avoiding user biases that might accompany manual sorting. We anticipate that this protocol will empower in particular environmental and host-associated microbiome research with a versatile tool to elucidate the metabolic contributions of microbial taxa within their complex communities. After a 1-d preparation of cells, sorting takes on the order of 4 h, depending on the number of cells required.