Prodigiosin regulates cancer metabolism through interaction with GLUT1.

In contrast to normal cells, cancer cells predominantly utilise glycolysis for ATP generation under aerobic conditions, facilitating proliferation and metastasis. Targeting glycolysis is effective for cancer treatment. Prodigiosin (PDG) is a natural compound with various bioactivities, including anticancer effects. However, the precise action mechanisms and molecular targets of PDG, which has demonstrated efficacy in regulating glucose metabolism in cancer cells, remain elusive. Here, we aimed to investigate the anti-cancer activity of PDG and mechanism in cancer metabolism. PDG regulated cancer metabolism by suppressing intracellular ATP production rate and levels. It inhibited glycolysis and mitochondrial oxidative phosphorylation, impeding ATP production dependent on both glycolysis and mitochondrial respiration. Moreover, it inhibited cellular glucose uptake by directly interacting with glucose transporter 1 without affecting its mRNA or protein levels in HCT116 cells. We provide insights into the anti-cancer effects of PDG mediated via cancer metabolism regulation, suggesting its therapeutic potential for cancer.

Thermal activation energy on electrical degradation process in BaTiO3 based multilayer ceramic capacitors for lifetime reliability.

For a high capacitance and high lifetime reliability of multilayer ceramic capacitors for automotive applications, the activation energy on thermal activation process can typically be calculated by using Arrhenius based Prokopowicz-Vaskas equation as a method for lifetime prediction. In this study, it is clearly observed that the activation energy shows to be constant in the range of ~ 1.5 eV for the prototype MLCCs, higher than the activation energy values of ~ 1.0 eV related to the motion or diffusion of oxygen vacancies reported in the previous literature. The activation energy value of ~ 1.5 eV for three prototype MLCCs is close to a half the energy band gap (Eg/2 ≈ 1.6 eV) of BaTiO3 obtained from specific environment, where oxygen vacancies are stabilized by external containment such as the effect of rare earth oxide additives. Due to an obvious difference in activation energy values, it difficult to explain the conduction mechanism for failure by only oxygen vacancy migration. Therefore, the concepts of electronic processes and oxygen vacancy should be considered together to understand conduction mechanism for failure of BaTiO3-based MLCCs in thermal activation processes. It can be useful as an indicator for future MLCC development with high lifetime reliability.

Feasibility study of computed tomography texture analysis for evaluation of canine primary adrenal gland tumors.

Objective: This study aimed to investigate the feasibility of computed tomography (CT) texture analysis for distinguishing canine adrenal gland tumors and its usefulness in clinical decision-making. Materials and methods: The medical records of 25 dogs with primary adrenal masses who underwent contrast CT and a histopathological examination were retrospectively reviewed, of which 12 had adenomas (AAs), 7 had adenocarcinomas (ACCs), and 6 had pheochromocytomas (PHEOs). Conventional CT evaluation of each adrenal gland tumor included the mean, maximum, and minimum attenuation values in Hounsfield units (HU), heterogeneity of the tumor parenchyma, and contrast enhancement (type, pattern, and degree), respectively, in each phase. In CT texture analysis, precontrast and delayed-phase images of 18 adrenal gland tumors, which could be applied for ComBat harmonization were used, and 93 radiomic features (18 first-order and 75 second-order statistics) were extracted. Then, ComBat harmonization was applied to compensate for the batch effect created by the different CT protocols. The area under the receiver operating characteristic curve (AUC) for each significant feature was used to evaluate the diagnostic performance of CT texture analysis. Results: Among the conventional features, PHEO showed significantly higher mean and maximum precontrast HU values than ACC (p < 0.05). Eight second-order features on the precontrast images showed significant differences between the adrenal gland tumors (p < 0.05). However, none of them were significantly different between AA and PHEO, or between precontrast images and delayed-phase images. This result indicates that ACC exhibited more heterogeneous and complex textures and more variable intensities with lower gray-level values than AA and PHEO. The correlation, maximal correlation coefficient, and gray level non-uniformity normalized were significantly different between AA and ACC, and between ACC and PHEO. These features showed high AUCs in discriminating ACC and PHEO, which were comparable or higher than the precontrast mean and maximum HU (AUC = 0.865 and 0.860, respectively). Conclusion: Canine primary adrenal gland tumor differentiation can be achieved with CT texture analysis on precontrast images and may have a potential role in clinical decision-making. Further prospective studies with larger populations and cross-validation are warranted.

The Fatal Role of Enterohaemorrhagic Escherichia coli Shiga Toxin-associated Extracellular Vesicles in Host Cells.

Enterohemorrhagic Escherichia coli (EHEC) is a specific subset of Shiga toxin-producing Escherichia coli (STEC) strains that are characterized by their ability to cause bloody diarrhea (hemorrhagic colitis) and potentially life-threatening, extraintestinal complications such as hemolytic uremic syndrome (HUS), which is associated with acute renal failure., contributing to severe clinical outcomes. The Shiga toxins (Stxs), produced by EHEC, are primary virulence factors. These potent cytotoxins are composed of one enzymatically active A subunit (StxA) and five receptor-binding B subunits (StxB). Although the toxins are primarily associated with cytotoxic effects, they also elicit other pathogenic consequences due to their induction of a number of biological processes, including apoptosis through ER-stress, pro-inflammatory responses, autophagy, and post-translational modification (PTM). Moreover, several studies have reported the association between Stxs and extracellular vesicles (EVs), including microvesicles and exosomes, demonstrating that Stx-containing EVs secreted by intoxicated macrophages are taken up by recipient cells, such as toxin-sensitive renal proximal tubular epithelial cells. This mechanism likely contributes to the spreading of Stxs within the host, and may exacerbate gastrointestinal illnesses and kidney dysfunction. In this review, we summarize recent findings relating to the host responses, in different types of cells in vitro and in animal models, mediated by Stxs-containing exosomes. Due to their unique properties, EVs have been explored as therapeutic agents, drug delivery systems, and diagnostic tools. Thus, potential therapeutic applications of EVs in EHEC Stxs-mediated pathogenesis are also briefly reviewed.

Pseudomonas stutzeri PM101005 inhaled with atmospheric particulate matter induces lung damage through inflammatory responses.

Atmospheric particulate matter (PM) contains a mixture of chemical and biological elements that pose threat to human health by increasing susceptibility to respiratory diseases. Although the identification of the microorganisms composing the PM has been assessed, their immunological impacts are still questionable. Here, we examined the mechanisms responsible for the pathogenicity of Pseudomonas stutzeri PM101005 (PMPS), a bacterium isolated from fine dust, in lung epithelial cells, alveolar cells, and macrophages. Relative to its comparative strain Pseudomonas stutzeri (PS), infections with PMPS induced higher production of inflammatory cytokines and chemokines, mediated by the activation of NF-κB and MAPK signaling pathways. Additionally, with three-dimensional (3D) airway spheroids which mimic the human bronchial epithelium, we confirmed that PMPS infections lead to relatively higher induction of pro-inflammatory cytokines than PM infections. Consistent results were observed in murine models as the infections with PMPS provoked greater inflammatory responses than the infections with PS. These PMPS-induced responses were mediated by the signaling pathways of the Toll-like receptors (TLRs), which regulated PMPS infection and played an important role in the expression of the antibiotic peptide ß-defensin 3 (BD3) that suppressed PMPS proliferation. Moreover, PM pretreatment enhanced inflammatory responses and tissue damage of PMPS, while reducing BD3 expression. Overall, these results indicate that PM-isolated PMPS induce TLR-mediated inflammatory responses in lung tissues, and contributes to the understanding of the etiology of PM-induced respiratory damage.

Six weeks of whole-body vibration improves fine motor accuracy, functional mobility and quality of life in people with multiple sclerosis.

People with multiple sclerosis (MS) suffer from sensorimotor deficits with the distal extremities being more severely affected than proximal ones. Whole-body vibration (WBV) training is known to enhance voluntary activation and coordination in healthy people. However, evidence about beneficial effects of WBV in MS patients is scarce. The current study aimed to investigate if six weeks of WBV enhances motor function in the ankle joint, coordination and quality of life in patients suffering from severe MS. In a longitudinal design, changes in motor function and quality of life were assessed before and after a 6-week control period without a training (CON) and a 6-week WBV training (2-3x/week) in 15 patients (53 ±10 years) with advanced MS (EDSS 3-6.5). Before CON (t0), after CON (t1) and after WBV(t2), outcome measures included (1) active range of motion (aROM) and (2) motor accuracy at the ankle joint, (3) functional mobility (Timed "Up & Go" test with preferred and non-preferred turns) and (4) physical and psychological impact of MS (MSIS-29 questionnaire). For (1) and (2), the stronger (SL) and the weaker leg (WL) were compared. After WBV, aROM (1) did not change (SL p = 0.26, WL p = 0.10), but was diminished after CON (SL -10% p = 0.06, WL -14% p = 0.03) with significant group differences (Δgroup WL p = 0.02). Motor accuracy in SL (2) was improved during dorsal flexion after WBV (p = 0.01, Δgroup p = 0.04) and deteriorated during plantar flexion after CON (p = 0.01, Δgroup p = 0.04). Additionally, participants (3) improved their functional mobility at the preferred turn (p = 0.04) and (4) ranked their quality of life higher solely after WBV (p = 0.05), without any differences between groups. However, values correlated significantly between angular precision and aROM as well as functional mobility. No further changes occurred. The results point towards an interception of degenerating mono-articular mobility and improvement of accuracy in the ankle joint. The motor effects after WBV are in line with enhanced perception of quality of life after six weeks which is why WBV could be a stimulus to enable greater overall autonomy in MS patients.

Inhibition of O-GlcNAcylation protects from Shiga toxin-mediated cell injury and lethality in host.

Shiga toxins (Stxs) produced by enterohemorrhagic Escherichia coli (EHEC) are the major virulence factors responsible for hemorrhagic colitis, which can lead to life-threatening systemic complications including acute renal failure (hemolytic uremic syndrome) and neuropathy. Here, we report that O-GlcNAcylation, a type of post-translational modification, was acutely increased upon induction of endoplasmic reticulum (ER) stress in host cells by Stxs. Suppression of the abnormal Stx-mediated increase in O-GlcNAcylation effectively inhibited apoptotic and inflammatory responses in Stx-susceptible cells. The protective effect of O-GlcNAc inhibition for Stx-mediated pathogenic responses was also verified using three-dimensional (3D)-cultured spheroids or organoids mimicking the human kidney. Treatment with an O-GlcNAcylation inhibitor remarkably improved the major disease symptoms and survival rate for mice intraperitoneally injected with a lethal dose of Stx. In conclusion, this study elucidates O-GlcNAcylation-dependent pathogenic mechanisms of Stxs and demonstrates that inhibition of aberrant O-GlcNAcylation is a potential approach to treat Stx-mediated diseases.

Escherichia coli Shiga Toxins and Gut Microbiota Interactions.

Escherichia coli (EHEC) and Shigella dysenteriae serotype 1 are enterohemorrhagic bacteria that induce hemorrhagic colitis. This, in turn, may result in potentially lethal complications, such as hemolytic uremic syndrome (HUS), which is characterized by thrombocytopenia, acute renal failure, and neurological abnormalities. Both species of bacteria produce Shiga toxins (Stxs), a phage-encoded exotoxin inhibiting protein synthesis in host cells that are primarily responsible for bacterial virulence. Although most studies have focused on the pathogenic roles of Stxs as harmful substances capable of inducing cell death and as proinflammatory factors that sensitize the host target organs to damage, less is known about the interface between the commensalism of bacterial communities and the pathogenicity of the toxins. The gut contains more species of bacteria than any other organ, providing pathogenic bacteria that colonize the gut with a greater number of opportunities to encounter other bacterial species. Notably, the presence in the intestines of pathogenic EHEC producing Stxs associated with severe illness may have compounding effects on the diversity of the indigenous bacteria and bacterial communities in the gut. The present review focuses on studies describing the roles of Stxs in the complex interactions between pathogenic Shiga toxin-producing E. coli, the resident microbiome, and host tissues. The determination of these interactions may provide insights into the unresolved issues regarding these pathogens.

Potential of MALDI-TOF-based serum N-glycan analysis for the diagnosis and surveillance of breast cancer.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based serum N-glycan analysis has gained acknowledgment for the diagnosis of breast cancer in recent years. In this study, the possibilities of expanding its application for breast cancer management and surveillance were discovered and evaluated. First, a novel MALDI-TOF platform, IDsys RT, was confirmed to be effective for breast cancer analysis, showing a maximum area under the curve of 0.91. Multiple N-glycan markers were identified and validated using this process, and they were found to be applicable for differentiating recurring breast cancer samples from healthy control or ordinary breast cancer samples. Recurrence samples were especially distinct from non-recurrence samples when N-glycan signatures were sampled in multiple time points and monitored via MALDI-TOF, throughout the therapy. These results suggested the feasibility of MALDI-TOF-based N-glycan analysis for tracking the molecular signatures of breast cancer and predicting recurrence.

Exosomes released from Shiga toxin 2a-treated human macrophages modulate inflammatory responses and induce cell death in toxin receptor expressing human cells.

Shiga toxins (Stxs) produced by Stx-producing Escherichia coli are the primarily virulence factors of hemolytic uremic syndrome and central nervous system (CNS) impairment. Although the precise mechanisms of toxin dissemination remain unclear, Stxs bind to extracellular vesicles (EVs). Exosomes, a subset of EVs, may play a key role in Stx-mediated renal injury. To test this hypothesis, we isolated exosomes from monocyte-derived macrophages in the presence of Stx2a or Stx2 toxoids. Macrophage-like differentiated THP-1 cells treated with Stxs secreted Stx-associated exosomes (Stx-Exo) of 90-130 nm in diameter, which induced cytotoxicity in recipient cells in a toxin receptor globotriaosylceramide (Gb3 )-dependent manner. Stx2-Exo engulfed by Gb3 -positive cells were translocated to the endoplasmic reticulum in the human proximal tubule epithelial cell line HK-2. Stx2-Exo contained pro-inflammatory cytokine mRNAs and proteins and induced more severe inflammation than purified Stx2a accompanied by greater death of target cells such as human renal or retinal pigment epithelial cells. Blockade of exosome biogenesis using the pharmacological inhibitor GW4869 reduced Stx2-Exo-mediated human renal cell death. Stx2-Exo isolated from human primary monocyte-derived macrophages activated caspase 3/7 and resulted in significant cell death in primary human renal cortical epithelial cells. Based on these results, we speculate that Stx-containing exosomes derived from macrophages may exacerbate cytotoxicity and inflammation and trigger cell death in toxin-sensitive cells. Therapeutic interventions targeting Stx-containing exosomes may prevent or ameliorate Stx-mediated acute vascular dysfunction.

Acute whole-body vibration reduces post-activation depression in the triceps surae muscle.

PURPOSE: Acute whole-body vibration (WBV) is known to enhance neuromuscular activation. Especially mechanisms which act presynaptically are discussed to be involved in this modulation, but evidence is still limited. Therefore, this study aimed to investigate if 2 min of WBV might impact the premotoneuronal mechanism of post-activation depression (PAD). METHODS: PAD in m. soleus was assessed by paired-pulse stimulation in 28 healthy participants prior, 2 min, 4 min and 10 min after 2 min of side-alternating WBV (10 Hz, 2 mm). Methodologies involved electromyography (m. soleus, m. tibialis anterior) and goniometric recordings (ankle, knee joint). H-reflexes were elicited with peripheral nerve stimulation and assessed by means of conditioned H-reflexes (ISI 1 s, Hcond) versus control H-reflexes (ISI10, H). RESULTS: Hcond/H was significantly enhanced by +55% (2 min), +32% (4 min) and +35% (10 min) following WBV (P < 0.05). Baseline muscle activity and joint positions were shown to be reliable (Cronbach's α values >0.990) throughout the testing procedure. CONCLUSION: Vibratory-induced spinal inhibition is accompanied by diminished PAD at the presynaptic terminals which interconnect the Ia afferents with the α-motoneuron. Functionally, the PAD reduction might explain enhanced motor performance following vibration therapy, but future studies will be needed to verify this assumption.

Breast cancer diagnosis by analysis of serum N-glycans using MALDI-TOF mass spectroscopy.

Blood and serum N-glycans can be used as markers for cancer diagnosis, as alterations in protein glycosylation are associated with cancer pathogenesis and progression. We aimed to develop a platform for breast cancer (BrC) diagnosis based on serum N-glycan profiles using MALDI-TOF mass spectroscopy. Serum N-glycans from BrC patients and healthy volunteers were evaluated using NosQuest's software "NosIDsys." BrC-associated "NosID" N-glycan biomarkers were selected based on abundance and NosIDsys analysis, and their diagnostic potential was determined using NosIDsys and receiver operating characteristic curves. Results showed an efficient pattern recognition of invasive ductal carcinoma patients, with very high diagnostic performance [area under the curve (AUC): 0.93 and 95% confidence interval (CI): 0.917-0.947]. We achieved effective stage-specific differentiation of BrC patients from healthy controls with 82.3% specificity, 84.1% sensitivity, and 82.8% accuracy for stage 1 BrC and recognized hormone receptor-2 and lymph node invasion subtypes based on N-glycan profiles. Our novel technique supplements conventional diagnostic strategies for BrC detection and can be developed as an independent platform for BrC screening.

Enhanced production of styrene by engineered Escherichia coli and in situ product recovery (ISPR) with an organic solvent.

BACKGROUND: Styrene is a large-volume commodity petrochemical, which has been used in a wide range of polymer industry as the main building block for the construction of various functional polymers. Despite many efforts to produce styrene in microbial hosts, the production titers are still low and are not enough to meet the commercial production of styrene. RESULTS: Previously, we developed a high L-phenylalanine producer (E. coli YHP05), and it was used as a main host for de novo synthesis of styrene. First, we introduced the co-expression system of phenylalanine-ammonia lyase (PAL) and ferulic acid decarboxylase (FDC) genes for the synthesis of styrene from L-phenylalanine. Then, to minimize cell toxicity and enhance the recovery of styrene, in situ product recovery (ISPR) with n-dodecane was employed, and culture medium with supplementation of complex sources was also optimized. As a result, 1.7 ± 0.1 g/L of styrene was produced in the flask cultures. Finally, fed-batch cultivations were performed in lab-scale bioreactor, and to minimize the loss of volatile styrene during the cultivation, three consecutive bottles containing n-dodecane were connected to the air outlet of bioreactor for gas-stripping. To conclude, the total titer of styrene was as high as 5.3 ± 0.2 g/L, which could be obtained at 60 h. CONCLUSION: We successfully engineered E. coli strain for the de novo production of styrene in both flask and fed-batch cultivation, and could achieve the highest titer for styrene in bacterial hosts reported till date. We believe that our efforts in strain engineering and ISPR strategy with organic solvent will provide a new insight for economic and industrial production of styrene in a biological platform.

Whole-body vibration impedes the deterioration of postural control in patients with multiple sclerosis.

OBJECTIVE: The current study aimed to investigate if whole-body vibration (WBV) might attenuate the processing functional and neuromuscular degeneration of postural control in patients with MS. DESIGN: Performance in postural control was assessed before and after 6 weeks of a control (CON) and a WBV intervention period. SETTING: Laboratory at the University of Freiburg & home-based training PARTICIPANTS: Out of 29 interested participants, 15 subjects with severe MS fit inclusion criteria. MAIN OUTCOME MEASURES: Centre of pressure displacement (COP), muscle activity and co-contraction indices of m. soleus (SOL), gastrocnemius medialis (GM), tibialis anterior (TA), biceps (BF) and rectus femoris (RF) as well as SOL H/M-ratios. RESULTS: After CON, COP was significantly enhanced with reduced muscle activity in RF and diminished shank muscle co-contraction. After WBV, no changes were observed in COP and neuromuscular control. However, over time, TA activity was reduced, but with no changes in muscle activation of SOL, GM and BF or H/M-ratios. CONCLUSIONS: After CON, MS patients experienced substantial deteriorations in postural control which have previously been associated with greater postural instability. No further disease-associated deteriorations were observed following the intervention. Thus, WBV might alleviate neurodegeneration of postural control in people with MS.

Posttraumatic Embitterment Disorder in Patients with Chronic Kidney Disease.

OBJECTIVE: Posttraumatic embitterment disorder (PTED), a subgroup of an adjustment disorder, is a feeling with anger and helplessness. Hemodialysis may be a trigger event leading to PTED. We investigated the prevalence of PTED in patients with each categorized stages of chronic kidney disease (CKD) and the association between PTED and depression and functional impairment. METHODS: Patients were categorized into three groups according to the stages of CKD (stage I-II, III-IV, and V). CKD (I-II) group was defined as estimated glomerular filtration rate (eGFR) ＞60 ml/min/1.73 m2, CKD (III-IV) group as eGFR ＜60 ml/min/1.73 m2, and CKD (V) group as CKD stage V including patients ongoing hemodialysis. Patients were assessed for the prevalence of PTED, depression, and decreased quality of life by using the scale of PTED, Patient Health Questionnaire-9 (PHQ-9), and EuroQol Five Dimensional Questionnaires, Visual Analogue Scale (EQ-5D-VAS), respectively. RESULTS: A total of 445 patients were analyzed. The number of patients in CKD (I-II) was 166, CKD (III-IV) was 172, and CKD (V) was 107. Multivariate analysis by binomial logistic regression demonstrated that CKD (V) was significantly associated with the prevalence of PTED (odds ratio, 4.13; 95% confidence interval, 1.56-15.6; p =0.006) after adjustment for age, gender, and diabetes mellitus. Also, a significant correlation existed between PTED and EQ-5D-VAS in all stages, but the correlation was nonsignificant between PTED and PHQ-9 score in group CKD (V). CONCLUSION: The findings suggest that PTED is underdiagnosed in CKD patients. Acknowledgment and diagnosis of PTED in CKD patients may lead to a better quality of life.

Stimulus Prediction and Postural Reaction: Phase-Specific Modulation of Soleus H-Reflexes Is Related to Changes in Joint Kinematics and Segmental Strategy in Perturbed Upright Stance.

Anticipation determines the timing and efficiency of human motor performance. This study aimed to evaluate the effect of stimulus anticipation on proactive (prior to the event) and reactive (after the event) postural adjustments in response to perturbations. Postural set was manipulated by providing either (i) predictable, (ii) unpredictable, or (iii) cheated perturbations which require balance corrections to maintain postural stability. In 29 subjects, a protocol of anterior and posterior perturbations was applied for the conditions (i-iii). Center of pressure (COP) displacement, ankle, knee, and hip joint kinematics and electromyographic activity (EMG) of the soleus (SOL) and tibialis anterior (TA) muscles were recorded prior (PRE) and after posterior perturbations. SOL H-reflexes at the peak of the short-, medium- ,and long-latency responses (SLR, MLR, LLR) were assessed. For conditions (i to iii) EMG activity and COP differed prior to perturbation onset (p < 0.05). After perturbation, results demonstrated a progressively increased H-reflex amplitude in the MLR and LLR (p < 0.05), delayed muscle activities (p < 0.05), and shifted activation patterns, with muscles of the proximal segment being more involved in the compensatory postural response (p < 0.05). COP displacements and ankle, knee, and hip joint deflections progressively increased (p < 0.05). Neuromechanical coupling showed positive correlations for the anticipation-induced changes in EMG activity and H-reflex amplitude with that of COP displacement (p < 0.05). In conclusion, proactive and reactive postural responses indicated setting dependent modulations of segmental and phasic muscle activation. A shift to proximal muscle groups and facilitated late reflex responses compensating for cheated or unpredicted perturbations was found to recover a safe body equilibrium. In consideration of the phase-specific adaptation and its interrelationship to the kinematics, it suggested that changes in stimulus prediction challenged the central nervous system to appropriately counteract the higher postural challenges. The outcomes of this experiment are of functional relevance for experimental and training settings involving perturbation stimuli. These findings provide fundamental information of the mechanisms underlying postural adjustments in response to external perturbations.

Inactivation of Clostridium difficile spore outgrowth by synergistic effects of nisin and lysozyme.

Inactivating Clostridium difficile spores is difficult, as they are resistant to heat, chemicals, and antimicrobials. However, this note describes inactivation of C. difficile spore outgrowth by incubation in a solution containing a germinant (1% (m/v) sodium taurocholate), co-germinants (1% (m/v) tryptose and 1% (m/v) NaCl), and natural antimicrobials (20 nmol·L-1 nisin and 0.2 mmol·L-1 lysozyme). Clostridium difficile spores were resistant to nisin and lysozyme but became susceptible during germination and outgrowth triggered and promoted by sodium taurocholate, tryptose, and NaCl. The degree of inactivation of germinated and outgrowing C. difficile spores by both nisin and lysozyme was greater than the sum of that by nisin and lysozyme individually, suggesting synergistic inactivation of C. difficile spores. The germinant, co-germinants, and natural antimicrobials used in this study are safe for human contact and consumption. Therefore, these findings will facilitate the development of a safe and effective method to inactivate C. difficile spore.

The Natural Course of Biopsy-Proven Isolated Microscopic Hematuria: a Single Center Experience of 350 Patients.

The increasing interest in healthcare and health screening events is revealing additional cases of asymptomatic isolated microscopic hematuria (IMH). However, a consensus of the evaluation and explanation of the IMH prognosis is controversial among physicians. Here, we present the natural course of IMH together with the pathological diagnosis and features to provide supportive data when approaching patients with IMH. We retrospectively evaluated 350 patients with IMH who underwent a renal biopsy between 2002 and 2011, and the pathological diagnosis and chronic histopathological features (glomerulosclerosis, interstitial fibrosis, and tubular atrophy) were reviewed. Deterioration of renal function was examined during follow up. The patients with IMH were evaluated for a mean of 86 months. IgA nephropathy was the most common diagnosis in 164 patients (46.9%). Chronic histopathological changes were observed in 166 (47.4%) but was not correlated with proteinuria or a decline in renal function. Ten patients developed proteinuria, and all of them had IgA nephropathy. Three patients progressed to chronic kidney disease with an estimated glomerular filtration rate < 60 mL/min/1.73 m(2) but none progressed to end stage renal disease. In conclusion, IMH had a generally benign course during 7-years of observation, although IgA nephropathy should be monitored if it progresses to proteinuria. Future prospective randomized studies may help conclude the long-term prognosis and lead to a consensus for managing IMH.

Serum ß2-Microglobulin Predicts Mortality in Peritoneal Dialysis Patients: A Prospective Cohort Study.

BACKGROUND/AIMS: ß2-Microglobulin (ß2-M) is a surrogate marker of middle-molecule uremic toxins and is associated with mortality in chronic hemodialysis patients. However, the impact of serum ß2-M levels on mortality in peritoneal dialysis (PD) patients is uncertain. The purpose of this study was to examine the association of serum ß2-M levels with all-cause mortality in PD patients. METHODS: A total of 771 PD patients were selected from the Clinical Research Center registry for end-stage renal disease cohort in Korea. Patients were categorized into 3 groups by tertiles of serum ß2-M levels. The primary outcome was all-cause mortality. RESULTS: The median value of serum ß2-M was 23.6 mg/l (interquartile range 14.8-33.4 mg/l), and the median follow-up period was 39 months. The Kaplan-Meier analysis showed that the all-cause mortality rate was significantly different according to tertiles of serum ß2-M in PD patients (p=0.03, log-rank). Multivariate Cox proportional analysis showed that the hazards ratio for all-cause mortality was 1.02 (95% CI 1.01-1.04, p=0.006) per 1 mg/l increase in ß2-M after adjustment for multiple confounding factors that relate to malnutrition and inflammation marker. However, serum ß2-M was not associated with all-cause mortality after adjustment for residual renal clearance. CONCLUSIONS: These results are supportive of the potential role of the serum ß2-M level as a predictor of mortality in PD patients.

Relationship Between Emphysema Severity and the Location of Lung Cancer in Patients With Chronic Obstructive Lung Disease.

OBJECTIVE: New phenotypes of chronic obstructive pulmonary disease (COPD) based on emphysema severity have been recognized recently. The purpose of this study was to determine the relationship between emphysema severity (phenotype) and lung cancer location in patients with COPD. MATERIALS AND METHODS: Four hundred patients with 405 primary lung cancers confirmed pathologically between January 2010 and March 2014 were included in the study. Of these, 193 patients received a diagnosis of COPD according to the Global Initiative for Chronic Obstructive Lung Disease guidelines. We scored emphysema severity (0-4) on thin-section CT and assigned the anatomic tumor location of lung cancer as peripheral or central. RESULTS: Patients with COPD had a higher proportion of centrally located lung cancer compared with those without COPD (36.4% vs 17.4%; p < 0.001). In patients with COPD, lower emphysema grades (odds ratio [OR], 0.69; 95% CI, 0.51-0.93; p = 0.016) and reduced ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) (OR, 0.94; 95% CI, 0.89-0.99; p = 0.024) were associated with central location. After adjusting for age, smoking, and spirometry results, the proportion of central location was approximately four times higher in patients with lower emphysema grades (0-2, < 25%) than in those with severe grades (grade 4, > 51%). CONCLUSION: Lower emphysema grades and reduced FEV1/FVC seemed to be independent predictors of central location of lung cancer in COPD. Therefore, in patients with COPD with lower grade emphysema and airway-predominant disease, additional screening tools may have to be considered for central lung cancer detection along with thin-section CT.