Vibration reconstruction and optical feedback parameter evaluation based on the direction discrimination in self-mixing interferometry.

Laser diode-based self-mixing interferometry (SMI) is a promising technique for noncontact sensing and its industry. In this paper, a phase unwrapping method in the several optical feedback levels is proposed based on displacement direction. A novel, to the best of our knowledge, method for evaluating the optical feedback factor C simultaneously with the linewidth enhancement is proposed by taking into account the effect of the accuracy of the linewidth enhancement $ \alpha $ on the evaluated method for C based on the differential feature of vibration reconstruction signal. Simulations and experiments are conducted to verify the proposed method.

Rufomycin Targets ClpC1 Proteolysis in Mycobacterium tuberculosis and M. abscessus.

ClpC1 is an emerging new target for the treatment of Mycobacterium tuberculosis infections, and several cyclic peptides (ecumicin, cyclomarin A, and lassomycin) are known to act on this target. This study identified another group of peptides, the rufomycins (RUFs), as bactericidal to M. tuberculosis through the inhibition of ClpC1 and subsequent modulation of protein degradation of intracellular proteins. Rufomycin I (RUFI) was found to be a potent and selective lead compound for both M. tuberculosis (MIC, 0.02 µM) and Mycobacterium abscessus (MIC, 0.4 µM). Spontaneously generated mutants resistant to RUFI involved seven unique single nucleotide polymorphism (SNP) mutations at three distinct codons within the N-terminal domain of clpC1 (V13, H77, and F80). RUFI also significantly decreased the proteolytic capabilities of the ClpC1/P1/P2 complex to degrade casein, while having no significant effect on the ATPase activity of ClpC1. This represents a marked difference from ecumicin, which inhibits ClpC1 proteolysis but stimulates the ATPase activity, thereby providing evidence that although these peptides share ClpC1 as a macromolecular target, their downstream effects are distinct, likely due to differences in binding.

Deep learning based low-cost high-accuracy diagnostic framework for dementia using comprehensive neuropsychological assessment profiles.

BACKGROUND: The conventional scores of the neuropsychological batteries are not fully optimized for diagnosing dementia despite their variety and abundance of information. To achieve low-cost high-accuracy diagnose performance for dementia using a neuropsychological battery, a novel framework is proposed using the response profiles of 2666 cognitively normal elderly individuals and 435 dementia patients who have participated in the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD). METHODS: The key idea of the proposed framework is to propose a cost-effective and precise two-stage classification procedure that employed Mini Mental Status Examination (MMSE) as a screening test and the KLOSCAD Neuropsychological Assessment Battery as a diagnostic test using deep learning. In addition, an evaluation procedure of redundant variables is introduced to prevent performance degradation. A missing data imputation method is also presented to increase the robustness by recovering information loss. The proposed deep neural networks (DNNs) architecture for the classification is validated through rigorous evaluation in comparison with various classifiers. RESULTS: The k-nearest-neighbor imputation has been induced according to the proposed framework, and the proposed DNNs for two stage classification show the best accuracy compared to the other classifiers. Also, 49 redundant variables were removed, which improved diagnostic performance and suggested the potential of simplifying the assessment. Using this two-stage framework, we could get 8.06% higher diagnostic accuracy of dementia than MMSE alone and 64.13% less cost than KLOSCAD-N alone. CONCLUSION: The proposed framework could be applied to general dementia early detection programs to improve robustness, preciseness, and cost-effectiveness.

Activity of LCB01-0371, a Novel Oxazolidinone, against Mycobacterium abscessus.

Mycobacterium abscessus is a highly pathogenic drug-resistant rapidly growing mycobacterium. In this study, we evaluated the in vitro, intracellular, and in vivo activities of LCB01-0371, a novel and safe oxazolidinone derivative, for the treatment of M. abscessus infection and compared its resistance to that of other oxazolidinone drugs. LCB01-0371 was effective against several M. abscessus strains in vitro and in a macrophage model of infection. In the murine model, a similar efficacy to linezolid was achieved, especially in the lungs. We induced laboratory-generated resistance to LCB01-0371; sequencing analysis revealed mutations in rplC of T424C and G419A and a nucleotide insertion at the 503 position. Furthermore, LCB01-0371 inhibited the growth of amikacin-, cefoxitin-, and clarithromycin-resistant strains. Collectively, our data indicate that LCB01-0371 might represent a promising new class of oxazolidinones with improved safety, which may replace linezolid for the treatment of M. abscessus.

Insulin-like growth factor-II regulates bone sialoprotein gene transcription.

Insulin-like growth factor-I and -II (IGF-I and IGF-II) have been found in bone extracts of several different species, and IGF-II is the most abundant growth factor stored in bone. Bone sialoprotein (BSP) is a noncollagenous extracellular matrix glycoprotein associated with mineralized connective tissues. In this study, we have investigated the regulation of BSP transcription by IGF-II in rat osteoblast-like ROS17/2.8 cells. IGF-II (50 ng/ml) increased BSP mRNA and protein levels after 6-h stimulation, and enhanced luciferase activities of the constructs pLUC3 (-116 to +60), pLUC4 (-425 to +60), pLUC5 (-801 to +60) and pLUC6 (-938 to +60). Effects of IGF-II were inhibited by tyrosine kinase, extracellular signal-regulated kinase1/2 and phosphatidylinositol 3-kinase inhibitors, and abrogated by 2-bp mutations in cAMP response element (CRE), FGF2 response element (FRE) and homeodomain protein-binding site (HOX). The results of gel shift assays showed that nuclear proteins binding to CRE, FRE and HOX sites were increased by IGF-II (50 ng/ml) at 3 and 6 h. CREB1, phospho-CREB1, c-Fos and c-Jun antibodies disrupted the formation of the CRE-protein complexes. Dlx5 and Runx2 antibodies disrupted the FRE- and HOX-protein complex formations. These studies therefore demonstrated that IGF-II increased BSP transcription by targeting CRE, FRE and HOX elements in the proximal promoter of the rat BSP gene. Moreover, phospho-CREB1, c-Fos, c-Jun, Dlx5 and Runx2 transcription factors appear to be key regulators of IGF-II effects on BSP transcription.

A new scoring method of the mini-mental status examination to screen for dementia.

BACKGROUND: Although the Mini-Mental Status Examination (MMSE) is the most widely used screening instrument for dementia, it has several limitations. METHODS: We developed and validated a new scoring method of the MMSE, namely the short form of the MMSE (MMSE-S). RESULTS: The MMSE-S was more robust to demographic influences than the MMSE. The influence of education, in particular, was smaller in the MMSE-S compared to the MMSE (p < 0.01). The diagnostic accuracy of the MMSE-S for very mild to mild dementia was also better than that of the original MMSE (p < 0.0001). Its specificity, in particular, was higher than that of the original MMSE. In Korea, we could improve the post-test probability for dementia from 46.88 to 64.76% by employing the MMSE-S instead of the MMSE. We also provided optimal cut-off scores for dementia stratified by age, education, and gender, which may further improve the diagnostic accuracy of the MMSE-S for dementia. CONCLUSION: Due to its good accuracy and brevity, the MMSE-S may contribute to enhancing the cost-effectiveness of and accessibility to dementia screening as well as early diagnosis and treatment of dementia, particularly in low- and middle-income countries.

Exploring age-related changes in saccades during cognitive tasks in healthy adults.

Introduction: Although eye movements such as saccades are related to internal cognitive processes and are independent of visual processing, few studies have investigated whether non-visual cognitive tasks simultaneously affect horizontal and vertical saccades in younger and older adults. Methods: We recruited 28 younger adults aged 20-29 years and 26 older adults aged >60 years through advertisements in community settings. All participants were free of major psychiatric, neurological, or ocular diseases. All participants performed the mental arithmetic task (MAT) and verbal fluency task (VFT). The primary measures were saccade parameters, including frequency, mean amplitude, and mean velocity. Results: During MAT and VFT, the frequencies of horizontal and vertical saccades increased (p = 0.0005 for horizontal saccade in MAT; p < 0.0001 for horizontal saccade in VFT; p = 0.012 for vertical saccade in MAT; p = 0.001 for vertical saccade in VFT), but were comparable between MAT and VFT. The old group showed a slower vertical saccade than the young group during the tasks (p = 0.011 in the MAT phase; p = 0.006 in the VFT phase). The amplitude of the horizontal saccade decreased in both groups during MAT compared to the resting period (p = 0.013), but did not change significantly during VFT. Discussion: Saccade parameters can change during non-visual cognitive tasks with differences between age groups and saccade directions. This study significantly contributes to our understanding of the distinct dynamics of horizontal and vertical saccades across various age group in cognitive aging, despite its restricted focus on specific saccade parameters and cognitive tasks, and inclusion solely of cognitively normal individuals. This study highlights the importance of saccade analysis in elucidating age-related cognitive changes. In conclusion, saccades should be examined in future studies as a potential non-invasive biomarker for early detection of cognitive decline and neurodegenerative diseases.

Cognitive impairment in age-related macular degeneration and geographic atrophy.

PURPOSE: To investigate cognitive function in patients with early and late age-related macular degeneration (AMD) compared with an elderly, community-dwelling Korean population without AMD. DESIGN: Case-control study. PARTICIPANTS: We enrolled 170 AMD patients and 190 non-AMD community-based controls. METHODS: A comprehensive battery for cognitive function evaluation consisting of 15 psychological tests, including a depression evaluation test, was used. Cognitive function scores were adjusted for age, gender, education, and visual acuity (VA). We categorized AMD as early AMD, exudative AMD, or geographic atrophy. MAIN OUTCOME MEASURES: The primary outcome measure was the degree of cognitive impairment, as assessed by the Korean versions of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery, Benton Visual Retention Test, and Digit Span Test Forward and Backward. RESULTS: Patients with AMD showed lower global cognition scores than did normal controls (mean Mini-Mental State Examination [MMSE] score, 24.97 vs 25.99; P<0.001). Among cognitive functions, visuospatial function, verbal memory, visual memory, and frontal function were impaired in AMD patients relative to normal controls. The rate of mild cognitive impairment (MCI) was higher in AMD patients than in controls (52.4% vs 26.8%; P<0.001), with an odds ratio (OR) of 3.127 (95% confidence interval, 1.855-5.271) after adjustment for age, education, and VA. Geographic atrophy was associated with the highest risk of MCI (OR, 4.431; 95% confidence interval, 1.413-13.898) and a clinically significant reduction in MMSE scores (23.42) relative to the controls. There was a trend of worsening cognitive function test scores from the controls to the early AMD, then the exudative AMD, and finally the geographic atrophy patients, after adjustment for covariates. AMD patients with poor VA (≤20/100) had 6 times the risk of MCI as AMD patients with good or moderate VA (>20/100). CONCLUSIONS: Patients with AMD, especially those with the geographic atrophy subtype, are at greater risk for cognitive impairment than are non-AMD control subjects. In the visual rehabilitation of AMD patients, potential cognitive impairment should be taken into consideration.

Chemical modulation of SQSTM1/p62-mediated xenophagy that targets a broad range of pathogenic bacteria.

The N-degron pathway is a proteolytic system in which the N-terminal degrons (N-degrons) of proteins, such as arginine (Nt-Arg), induce the degradation of proteins and subcellular organelles via the ubiquitin-proteasome system (UPS) or macroautophagy/autophagy-lysosome system (hereafter autophagy). Here, we developed the chemical mimics of the N-degron Nt-Arg as a pharmaceutical means to induce targeted degradation of intracellular bacteria via autophagy, such as Salmonella enterica serovar Typhimurium (S. Typhimurium), Escherichia coli, and Streptococcus pyogenes as well as Mycobacterium tuberculosis (Mtb). Upon binding the ZZ domain of the autophagic cargo receptor SQSTM1/p62 (sequestosome 1), these chemicals induced the biogenesis and recruitment of autophagic membranes to intracellular bacteria via SQSTM1, leading to lysosomal degradation. The antimicrobial efficacy was independent of rapamycin-modulated core autophagic pathways and synergistic with the reduced production of inflammatory cytokines. In mice, these drugs exhibited antimicrobial efficacy for S. Typhimurium, Bacillus Calmette-Guérin (BCG), and Mtb as well as multidrug-resistant Mtb and inhibited the production of inflammatory cytokines. This dual mode of action in xenophagy and inflammation significantly protected mice from inflammatory lesions in the lungs and other tissues caused by all the tested bacterial strains. Our results suggest that the N-degron pathway provides a therapeutic target in host-directed therapeutics for a broad range of drug-resistant intracellular pathogens.Abbreviations: ATG: autophagy-related gene; BCG: Bacillus Calmette-Guérin; BMDMs: bone marrow-derived macrophages; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CFUs: colony-forming units; CXCL: C-X-C motif chemokine ligand; EGFP: enhanced green fluorescent protein; IL1B/IL-1ß: interleukin 1 beta; IL6: interleukin 6; LIR: MAP1LC3/LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; Mtb: Mycobacterium tuberculosis; MTOR: mechanistic target of rapamycin kinase; NBR1: NBR1 autophagy cargo receptor; OPTN: optineurin; PB1: Phox and Bem1; SQSTM1/p62: sequestosome 1; S. Typhimurium: Salmonella enterica serovar Typhimurium; TAX1BP1: Tax1 binding protein 1; TNF: tumor necrosis factor; UBA: ubiquitin-associated.

Prevalence of painful bladder syndrome/interstitial cystitis-like symptoms in women: a population-based study in Korea.

OBJECTIVE: Despite growing clinical interest in painful bladder syndrome/interstitial cystitis (PBS/IC, also known as bladder pain syndrome), estimating its prevalence is difficult because of its variable presentation and the lack of clear diagnostic criteria. In this study, we estimated the prevalence of PBS/IC-like urinary symptoms in adult women in the general population of South Korea. METHODS: A population-based cross-sectional telephone survey was conducted among 2,323 women (18-71 years of age), selected by geographically stratified random sampling, based on Korean census data. The survey was performed by trained interviewers between September 22, 2008, and October 6, 2008. All participants were interviewed by telephone using a validated questionnaire, the O'Leary-Sant IC Symptom and Problem (OLS) index. Women with high symptom and problem index scores of 12 or greater and scores of two or greater for pain and nocturia symptoms were considered to have "probable PBS/IC," according to previously suggested criteria. RESULTS: After exclusions, a total of 2,300 respondents were included. The severity of symptoms increased with age. Eight respondents (0.35%) reported severe symptoms and problems (OLS survey scores of ≥12). Of these, six (261/100,000 or 0.26%, 95% CI 242-278) met previously suggested criteria for probable PBS/IC. CONCLUSION: The prevalence of PBS/IC-like urinary symptoms in South Korean women appeared to be lower than in Europe and the United States, and similar to that of Japan, according to common criteria. Screening for symptoms that are consistent with the disease may improve our understanding of its true prevalence.

Functional impairment in the diagnosis of mild cognitive impairment.

The criterion on functional activity in the revised diagnostic criteria for mild cognitive impairment (MCI) seems to be conceptually and operationally problematic.We investigated the predictive validity for dementia of this criterion in 140 patients with MCI who participated in the baseline study of the Korean Longitudinal Study on Health and Aging and completed 18-month follow-up evaluation (mean duration of follow-up, 1.57±0.24 y). Annual conversion rates to dementia were compared between the patients who fulfilled the criterion on functional activity and those who did not. Annual conversion rates to dementia of the patients who fulfilled the criterion on functional activity was 4.76%, whereas that of the patients with MCI who did not was 33.07%, indicating that the criterion on functional activity was a significant negative predictor of dementia (odds ratio=0.12). Re-revision of the criterion on functional activity may be warranted to solve its conceptual and operational ambiguities.

Korean version of frontal assessment battery: psychometric properties and normative data.

BACKGROUND: We developed the Korean version of the Frontal Assessment Battery (FAB-K), evaluated its psychometric properties and constructed normative data for Korean elders. METHODS: FAB-K was administered to 300 Alzheimer's disease (AD) patients and 635 normal controls. Reliability of FAB-K was evaluated by testing its internal consistency, test-retest and inter-rater reliabilities. Validity of FAB-K was evaluated by testing discriminant validity for AD and concurrent validity with other frontal function tests. Age- and education-specific normative data of FAB-K were developed. RESULTS: Cronbach's alpha, inter-rater reliability and test-retest reliability of FAB-K were 0.802, 0.980 (p < 0.001) and 0.820 (p < 0.001), respectively. FAB-K exhibited significant correlations with the scores of MMSE and other frontal function tests (p < 0.01). Total and item scores of FAB-K were lower in AD patients than in controls and became worse as clinical dementia rating increased (F = 192.026, d.f. = 4, p < 0.001). The optimal cut-off score of FAB-K for AD was determined as 10/11, where sensitivity and specificity for AD were 0.717 and 0.827, respectively. Normative data were stratified by 3 age groups and 4 education groups. CONCLUSION: The FAB-K is a valid and reliable instrument for evaluating frontal dysfunction, and may be useful for screening AD.

Development of the Subjective Memory Complaints Questionnaire.

AIM: We aimed to evaluate the psychometric properties of the Subjective Memory Complaints Questionnaire (SMCQ). METHODS: The reliability of the SMCQ was evaluated by testing its internal consistency and test-retest reliability. Pearson correlation analyses were performed to assess the concurrent validity. Confirmatory factor analysis was used to evaluate the construct validity. Diagnostic ability for dementia was tested with receiver operator characteristic curve analyses. RESULTS: Cronbach's alpha coefficient and intraclass correlation coefficients of the SMCQ were 0.864 and 0.828 (p < 0.001), respectively. The SMCQ scores were significantly correlated with the scores on Camdex Memory Complaint Questionnaire, Seoul Informant Report Questionnaire for Dementia and cognitive tests from the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) neuropsychological test battery (p < 0.01). The results of confirmatory factor analyses confirmed that the SMCQ consisted of subjective memory complaints (SMC) for general memory and for everyday memory. The SMCQ score discriminated well between nondemented elderly without dementia and those with dementia (p < 0.01). The area under the curve value of the SMCQ was 0.84, indicating that it had high diagnostic ability. CONCLUSION: The SMCQ was found to be a brief, reliable and valid questionnaire for evaluating SMC. It might be useful for evaluating the cognition of elderly subjects when reliable informants are not available.

Cardiac amyloidosis in a patient with multiple myeloma: a case report and review of literature.

We report a case of a 52-year-old man with multiple myeloma and rapidly progressive heart failure who died unexpectedly from a probable arrhythmia. Postmortem examination revealed infiltrative amyloid cardiomyopathy, a rare cause of predominantly diastolic myocardial disease. Cardiac amyloidosis should be considered in any patient presenting with congestive heart failure, preserved systolic function, and a discrepancy between a low QRS voltage on electrocardiography and an apparent left ventricular hypertrophy on sonogram. The pattern of left ventricular diastolic dysfunction changes during the course of amyloidosis and the classically described restrictive physiology occurs only in advanced stages of the disease.

Rg6, a rare ginsenoside, inhibits systemic inflammation through the induction of interleukin-10 and microRNA-146a.

The immunobiological functions of Rg6, a rare ginsenoside from ginseng, have been largely unreported. In this paper, we demonstrate that Rg6 has a significant immunosuppressive function on Toll-like receptor (TLR) 4-induced systemic inflammatory responses. Rg6 was found to negatively regulate pro-inflammatory responses and severity in vivo, and thus induced recovery in mice with lipopolysaccharide (LPS)-induced septic shock and cecal ligation and puncture (CLP)-induced sepsis. Rg6 treatment also facilitated recovery in mice with LPS-induced lung damage via reduced neutrophil infiltration and tumor necrosis factor-α expression in lung tissues. Rg6 injection also downregulated pro-inflammatory cytokines and increased the levels of interleukin (IL)-10 in the serum of septic mice. Mechanistically, Rg6 did not induce TLR negative regulators, such as A20 and IRAK-M, in bone marrow-derived macrophages (BMDMs). Instead, addition of Rg6 to LPS-activated BMDMs augmented IL-10 expression, whereas it inhibited inflammatory signaling, such as by nuclear factor κB activation and mitogen-activated protein kinases. Furthermore, Rg6 significantly induced miR-146a, an operator miRNA for anti-inflammation, in BMDMs. Collectively, these data indicate that Rg6 inhibits inflammatory responses through the induction of IL-10 and miR-146a.

SIRT3 promotes antimycobacterial defenses by coordinating mitochondrial and autophagic functions.

SIRT3 (sirtuin 3), a mitochondrial protein deacetylase, maintains respiratory function, but its role in the regulation of innate immune defense is largely unknown. Herein, we show that SIRT3 coordinates mitochondrial function and macroautophagy/autophagy activation to promote anti-mycobacterial responses through PPARA (peroxisome proliferator activated receptor alpha). SIRT3 deficiency enhanced inflammatory responses and mitochondrial dysfunction, leading to defective host defense and pathological inflammation during mycobacterial infection. Antibody-mediated depletion of polymorphonuclear neutrophils significantly increased protection against mycobacterial infection in sirt3-/- mice. In addition, mitochondrial oxidative stress promoted excessive inflammation induced by Mycobacterium tuberculosis infection in sirt3-/- macrophages. Notably, SIRT3 was essential for the enhancement of PPARA, a key regulator of mitochondrial homeostasis and autophagy activation in the context of infection. Importantly, overexpression of either PPARA or TFEB (transcription factor EB) in sirt3-/- macrophages recovered antimicrobial activity through autophagy activation. Furthermore, pharmacological activation of SIRT3 enhanced antibacterial autophagy and functional mitochondrial pools during mycobacterial infection. Finally, the levels of SIRT3 and PPARA were downregulated and inversely correlated with TNF (tumor necrosis factor) levels in peripheral blood mononuclear cells from tuberculosis patients. Collectively, these data demonstrate a previously unappreciated function of SIRT3 in orchestrating mitochondrial and autophagic functions to promote antimycobacterial responses. Abbreviations: Ab: antibody; BCG: M. bovis Bacillus Calmette-Guérin; Baf-A1: bafilomycin A1; BMDMs: bone marrow-derived macrophages; CFU: colony forming unit; CXCL5: C-X-C motif chemokine ligand 5; EGFP: enhanced green fluorescent protein; ERFP: enhanced red fluorescent protein; FOXO3: forkhead box O3; HC: healthy controls; H&E: haematoxylin and eosin; HKL: honokiol; IHC: immunohistochemistry; IL1B: interleukin 1 beta; IL6: interleukin 6; IL12B: interleukin 12B; MDMs: monocyte-derived macrophages; MMP: mitochondrial membrane potential; Mtb: Mycobacterium tuberculosis; PBMC: peripheral blood mononuclear cells; PBS: phosphate buffered saline; PMN: polymorphonuclear neutrophil; PPARA: peroxisome proliferator activated receptor alpha; ROS: reactive oxygen species; SIRT3: sirtuin 3; TB: tuberculosis; TEM: transmission electron microscopy; TFEB: transcription factor EB; TNF: tumor necrosis factor.

The impact of tension-free vaginal tape on overactive bladder symptoms in women with stress urinary incontinence: significance of detrusor overactivity.

PURPOSE: We assessed the impact of the tension-free vaginal tape procedure on overactive bladder in women with stress urinary incontinence to determine the change in preoperative overactive bladder symptoms and the significance of detrusor overactivity in postoperative outcomes. MATERIALS AND METHODS: From January 2003 to December 2004 a total of 549 consecutive women with stress urinary incontinence underwent the tension-free vaginal tape procedure. Of these patients 180 (32.8%) had overactive bladder syndrome. Finally 132 women (mean age 53.2 years) with followup of at least 3 months were included in analysis. Patients with the overactive bladder syndrome with or without detrusor overactivity based on urodynamic study were subdivided into 94 (71.2%) patients with the overactive bladder syndrome without detrusor overactivity and 38 (28.8%) with the overactive bladder syndrome with detrusor overactivity. RESULTS: The complete resolution of all overactive bladder symptoms based on 3-day frequency volume chart and a validated questionnaire was demonstrated in 23.5% (31 of 132 patients). The detrusor overactivity present group showed significantly greater urinary leakage per 1-hour pad test, maximal detrusor pressure and detrusor pressure at maximal flow rate than the detrusor overactivity absent group. There was no significant difference in the 2 groups in terms of cure rate for stress urinary incontinence. The detrusor overactivity present group had a significantly higher resolution rate than the detrusor overactivity absent group for overactive bladder (36.8 vs 18.1 %, p = 0.021). CONCLUSIONS: The tension-free vaginal tape procedure can be performed in women with stress urinary incontinence and overactive bladder including urge incontinence even if the patient has detrusor overactivity on urodynamic study. However, patients should be fully advised of the possibility of persistent overactive bladder symptoms and treatment for those symptoms after tension-free vaginal tape should be considered.

Routine screening for classical azoospermia factor deletions of the Y chromosome in azoospermic patients with Klinefelter syndrome.

AIM: To evaluate the occurrence of classical azoospermia factor (AZF) deletions of the Y chromosome as a routine examination in azoospermic subjects with Klinefelter syndrome (KS). METHODS: Blood samples were collected from 95 azoospermic subjects with KS (91 subjects had a 47,XXY karyotype and four subjects had a mosaic 47,XXY/46,XY karyotype) and a control group of 93 fertile men. The values of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured. To determine the presence of Y chromosome microdeletions, polymerase chain reaction (PCR) of five sequence-tagged site primers (sY84, sY129, sY134, sY254, sY255) spanning the AZF region, was performed on isolated genomic DNA. RESULTS: Y chromosome microdeletions were not found in any of the 95 azoospermic subjects with KS. In addition, using similar conditions of PCR, no microdeletions were observed in the 93 fertile men evaluated. The level of FSH in KS subjects was higher than that in fertile men (38.2 +/- 10.3 mIU/mL vs. 5.4 +/- 2.9 mIU/mL, P < 0.001) and the testosterone level was lower than that in the control group (1.7 +/- 0.3 ng/mL vs. 4.3 +/- 1.3 ng/mL, P < 0.001). CONCLUSION: Our data and review of the published literature suggest that classical AZF deletions might not play a role in predisposing genetic background for the phenotype of azoospermic KS subjects with a 47,XXY karyotype. In addition, routine screening for the classical AZF deletions might not be required for these subjects. Further studies including partial AZFc deletions (e.g. gr/gr or b2/b3) are necessary to establish other mechanism underlying severe spermatogenesis impairment in KS.

Polypoid spindle cell carcinoma of the esophagus.

Rare histologic variants of esophageal cancer account for about 5% of cases. As its name suggests, polypoid spindle cell carcinoma of the esophagus (carcinosarcoma, pseudosarcoma) is comprised of both epithelial and spindle cell elements. The nomenclature reflects both the historical controversy over the lesion's cell of origin as well as its characteristic fungating intraluminal growth pattern. The authors report a case of polypoid spindle cell carcinoma of the esophagus that was preoperatively diagnosed as a visceral sarcoma.

Ohmyungsamycins promote antimicrobial responses through autophagy activation via AMP-activated protein kinase pathway.

The induction of host cell autophagy by various autophagy inducers contributes to the antimicrobial host defense against Mycobacterium tuberculosis (Mtb), a major pathogenic strain that causes human tuberculosis. In this study, we present a role for the newly identified cyclic peptides ohmyungsamycins (OMS) A and B in the antimicrobial responses against Mtb infections by activating autophagy in murine bone marrow-derived macrophages (BMDMs). OMS robustly activated autophagy, which was essentially required for the colocalization of LC3 autophagosomes with bacterial phagosomes and antimicrobial responses against Mtb in BMDMs. Using a Drosophila melanogaster-Mycobacterium marinum infection model, we showed that OMS-A-induced autophagy contributed to the increased survival of infected flies and the limitation of bacterial load. We further showed that OMS triggered AMP-activated protein kinase (AMPK) activation, which was required for OMS-mediated phagosome maturation and antimicrobial responses against Mtb. Moreover, treating BMDMs with OMS led to dose-dependent inhibition of macrophage inflammatory responses, which was also dependent on AMPK activation. Collectively, these data show that OMS is a promising candidate for new anti-mycobacterial therapeutics by activating antibacterial autophagy via AMPK-dependent signaling and suppressing excessive inflammation during Mtb infections.