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BACKGROUND Clostridioides difficile infection (CDI) is a common community-acquired and nosocomial infection that usually presents as colitis. C. difficile bacteremia (CDB) is a rare blood infection, with only a few cases recorded in the literature. We seek to expound on the current literature by detailing the clinical course of a patient with metastatic melanoma who developed CDB. CASE REPORT This case highlights the hospital course of a 51-year-old man admitted for a new onset of arrhythmia during the evaluation and management of a malignancy. The patient experienced hemodynamic collapse and rapid deterioration, which progressed to death. The etiology of death is thought to be septic shock due to CDB in the setting of multiple comorbidities. Aristolochic acid A manufacturer CONCLUSIONS The patient was predisposed to CDI because of the disruption of his intestinal milieu by the administration of a cephalosporin for the treatment of his suspected secondary bacterial peritonitis. His treatment with palliative radiation to his rectal mass placed him further at risk of CDI. We believe either of these could have contributed alone or synergistically to the development of his CDB.

Crohn's disease (CD) is characterized by uncontrolled inflammation of the intestine.

(

), a probiotic, stabilizes the intestinal wall. This study examined the changes in the CD activity index (CDAI) after taking

in patients with CD in clinical remission.

In this single hospital-based retrospective cohort study, the medical records of CD patients in clinical remission, who had received

for more than 6 months, were reviewed. The CDAI, BMI, and serum levels of hemoglobin (Hb), ferritin, iron, vitamin B12, folate, total protein, albumin, total cholesterol, CRP, and fecal calprotectin (FC) between the initiation and the 6th month were compared. The timing and reasons for the discontinuation were also investigated.

One hundred and fifty-four patients were included, and 92 patients, who received for more than 6 months, were analyzed. The changes in CDAI, BMI, Hb, and total cholesterol were significant as follows CDAI from 38.52 to 30.53 (p<0.01), BMI (kg/m

) from 23.38 to 23.97 (p<0.01), Hb (g/dL) from 13.73 to 14.03 (p<0.01), and total cholesterol (mg/dL) from 154.9 to 161.5 (p<0.01). On the other hand, the changes in FC, CRP, ferritin, vitamin B12, folate, total protein, and albumin were not statistically significant. Only one patient stopped due to a flare-up, but this was not believed to be related to the drug.

In patients with CD in remission,

appears to improve the CDAI, BMI, serum Hb, and total cholesterol level without safety issues. Further randomized controlled studies will be needed.

In patients with CD in remission, S. boulardii appears to improve the CDAI, BMI, serum Hb, and total cholesterol level without safety issues. Further randomized controlled studies will be needed.Most animals cannot digest cellulose but have symbiotic microbes that degrade the matrix polysaccharides of plant matter. Herbivorous and omnivorous marine fish are similarly expected to rely on symbiotic microbes, but reports to date on cellulase-producing bacteria in fish intestines are limited. Here, we report the isolation of new cellulase-producing bacteria from the marine omnivorous teleost, blackfish (Girella melanichthys), and the characterization of cellulase activity. Three strains of cellulase-producing bacteria sp. were isolated from the hindgut of wild G. melanichthys. The strains of cellulase-producing bacteria grew in medium with artificial seawater but not in NaCl alone. Growth was optimum at 20-35°C, but there was no growth at 40°C, suggesting adaptation in a marine environment at a low temperature. Isolates were identified to Microbulbifer sp., among which GL-2 strain produced a high enzyme activity. The GL-2 strain was further used for enzyme characterization with carboxymethyl cellulose (CMC) as the substrate. Maximum activity of the cellulase was observed at 60°C, and activity was more than 30% at 20°C, while commercial cellulase Enthiron showed an optimum activity at 50°C and 17% activity at 20°C. Hydrolytic products by GL-2 cellulase were cellobiose but not glucose, suggesting a deficiency of β-glucosidase activity. Active gel electrophoresis containing CMC showed five bands, suggesting several cellulolytic enzymes. The GL-2 strain and its enzyme are potential probiotics for aquaculture fish and the industrial production of cellobiose.Onychomycosis is a common and intractable superficial mycosis that occurs worldwide. Treatment with both oral and topical drugs is recommended, but the objective evaluation procedure to determine the efficacy of and the appropriate delivery system for the drugs remains controversial. This may be attributed to the lack of a reliable animal model that not only mirrors the pathophysiology of human onychomycosis but is also feasible. Therefore, we attempted to establish an animal model of onychomycosis using immunosuppressed guinea pigs and elucidate the pathophysiology of human onychomycosis. In the present study, we applied Trichophyton mentagrophytes TIMM2789 to the hind limb nails of corticosteroid-treated guinea pigs. The nails were examined macroscopically and histopathologically at 0, 14, and 42 days after a 2-week exposure period to the fungus. A large portion of the experimentally infected nails showed discoloration, which is an important clinical sign, and most infections were confirmed histopathologically in the deep layer of the nail plate at all time points. The infection rates at 0, 14, and 42 days after exposure were 39%, 61%, and 78%, respectively. Thus, we established an animal model of onychomycosis with good reproducibility and that might be appropriate for extrapolation to the pathophysiology of the human disease.The aim of the present work was to investigate the impact of maternal obesity on DNA methylation in ovulated oocytes, and to compare the response of in vitro-developing preimplantation embryos originating from control and obese mice to insulin. An intergenerational, diet-induced obesity model was used to produce outbred mice with an increased body weight and body fat. Two-cell and eight-cell embryos recovered from obese and control mice were cultured in a medium supplemented with 1 or 10 ng/ml insulin until blastocyst formation. In the derived blastocysts, cell proliferation, differentiation, and death rates were determined. The results of immunochemical visualization of 5-methylcytosine indicated a slightly higher DNA methylation in ovulated metaphase II oocytes recovered from obese females; however, the difference between groups did not reach statistical significance. Expanded blastocysts developed from embryos provided by control dams showed increased mean cell numbers (two and eight-cell embryos exposed to 10 ng/ml), an increased inner-cell-mass/trophectoderm ratio (two-cell embryos exposed to 1 ng/ml and eight-cell embryos exposed to 10 ng/ml), and a reduced level of apoptosis (two and eight-cell embryos exposed to 10 ng/ml). In contrast, embryos originating from obese mice were significantly less sensitive to insulin; indeed, no difference was recorded in any tested variable between the embryos exposed to insulin and those cultured in insulin-free medium. Real-time RT-PCR analysis showed a significant increase in the amount of insulin receptor transcripts in blastocysts recovered from obese dams. These results suggest that maternal obesity might modulate the mitogenic and antiapoptotic responses of preimplantation embryos to insulin.

Diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging in elderly. This study investigated the diagnostic ability of the HFA-PEFF scoring system in elderly patients (>75 years of age).Methods and ResultsThis study enrolled 286 subjects aged >75 years (130 men; mean [± SD] age 81.5±5.1 years) 95 healthy controls, 98 with hypertension (HT), and 93 with HFpEF. The HFA-PEFF score was calculated as a sum of points in functional, morphological, and biomarker domains. In the HFpEF group, 84%, 84%, and 70% of subjects met the major functional, morphological, and biomarker criteria for HFpEF, respectively. Thus, 73 subjects with HFpEF (78%) were diagnosed as having HFpEF using the HFA-PEFF scoring system. In contrast, among the healthy controls and subjects with HT, 52% and 72%, respectively, met the major functional criteria for HFpEF, 28% and 53%, respectively, met the morphological criteria, and 0% and 24%, respectively, met the biomarker criteria. As such, 32 subjects with HT (33%) were diagnosed with HFpEF. Even in the healthy control group, 72% were classified as having an intermediate probability of HFpEF, and 3 were diagnosed with HFpEF.

In the late elderly, the HFA-PEFF scoring system diagnosed subjects with HFpEF precisely. In addition, this scoring system may be able to detect early stage HFpEF in the subclinical population.

In the late elderly, the HFA-PEFF scoring system diagnosed subjects with HFpEF precisely. In addition, this scoring system may be able to detect early stage HFpEF in the subclinical population.

There is little data as to whether osteoprotegerin (OPG) is associated with target organ damage (TOD), so we evaluated the association in patients at high risk of coronary artery disease (CAD).Methods and ResultsA total of 349 patients who underwent invasive coronary angiography (ICA) for suspected CAD were prospectively recruited. During the index admission, 6 TOD parameters were collected extent of CAD, glomerular filtration rate (GFR), left ventricular mass index (LVMI), E/e', brachial-ankle pulse wave velocity (baPWV), and ankle-brachial index (ABI). Serum OPG levels were measured using enzyme-linked immunosorbent assay. The OPG level was significantly higher in patients with ≥1 TOD parameter than in those without (314±186 vs. 202±74 pg/mL, P<0.001). For each TOD parameter, the serum OPG level was significantly higher in patients with TOD than in those without (P<0.05 for each) except for ABI. In correlation analysis, OPG was significantly associated with GFR, LVMI, E/e', baPWV and ABI (P<0.05 for each). The OPG concentration increased proportionally with increasing TOD (P<0.001). Higher OPG concentrations (≥198 pg/mL) was significantly associated with the presence of TOD (odds ratio 3.22; 95% confidence interval 1.51-6.85; P=0.002) even after controlling for potential confounders.

Serum OPG level was significantly associated with a variety of TOD in patients undergoing ICA. OPG may be a useful marker for TOD and in the risk stratification of patients at high risk of CAD.

Serum OPG level was significantly associated with a variety of TOD in patients undergoing ICA. OPG may be a useful marker for TOD and in the risk stratification of patients at high risk of CAD.In vivo-mimic silkworm infection models with Mycobacterium avium and Mycobacterium intracellulare were newly established to evaluate the therapeutic effects of anti-M. avium complex (MAC) antibiotics. Silkworms raised at 37°C died within 72 hours of an injection of M. avium or M.intracellulare (2.5 × 107 colony-forming unit (CFU)/larva·g) into the hemolymph. Clinical anti-mycobacterial (tuberculosis) antibiotics were evaluated under these conditions. Clarithromycin, kanamycin, streptomycin, amikacin, and ciprofloxacin exerted therapeutic effects in a dose-dependent manner, which was consistent with those in the mouse model. Furthermore, three effective actinomycete culture broths were selected in the screening program of our microbial broth library using the silkworm model, and four active metabolites, ohmyungsamycins A and B (1 and 2), chartreusin (3), and griseoviridin (4), were identified. Among these compounds, 1 showed the lowest 50% effective dose (ED50) value (8.5 µg/larva·g), while 3 had the best ED50/minimum inhibitory concentration (MIC) ratio (7.

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