Proline-Hinged α-Helical Peptides Sensitize Gram-Positive Antibiotics, Expanding Their Physicochemical Properties to Be Used as Gram-Negative Antibiotics.

The outer membrane (OM) of Gram-negative bacteria is the most difficult obstacle for small-molecule antibiotics to reach their targets in the cytosol. The molecular features of Gram-negative antibiotics required for passing through the OM are that they should be positively charged rather than neutral, flat rather than globular, less flexible, or more increased amphiphilic moment. Because of these specific molecular characteristics, developing Gram-negative antibiotics is difficult. We focused on sensitizer peptides to facilitate the passage of hydrophobic Gram-positive antibiotics through the OM. We explored ways of improving the sensitizing ability of proline-hinged α-helical peptides by adjusting their length, hydrophobicity, and N-terminal groups. A novel peptide, 1403, improves the potentiation of rifampicin in vitro and in vivo and potentiates most Gram-positive antibiotics. The "sensitizer" approach is more plausible than those that rely on conventional drug discovery methods concerning drug development costs and the development of drug resistance.

Seroreactivity to Coxiella burnetii in an Agricultural Population and Prevalence of Coxiella burnetii Infection in Ticks of a Non-Endemic Region for Q Fever in South Korea.

Coxiella burnetii infects humans and wild and domesticated animals. Although reported cases on Jeju Island, off the coast of South Korea, are rare, the region is considered to have a high potential for Q fever. We investigated the seroprevalence of antibodies to C. burnetii in 230 farmers living in ten rural areas on Jeju Island between January 2015 and December 2019. Blood samples were collected and examined for C. burnetii Phase I/II IgM and IgG antibodies. Trained researchers collected ticks from rural areas. Clone XCP-1 16S ribosomal RNA gene sequencing was performed to identify Coxiella species from the collected ticks. The overall seroprevalence of antibodies to C. burnetii in farmers was 35.7%. The seroprevalence was significantly higher in fruit farmers. Of the collected ticks, 5.4% (19/351) of the Haemaphysalis longicornis ticks harbored C. burnetti. A high seroprevalence of antibodies to C. burnetii was observed in this region of Jeju Island, confirming that C. burnetti is endemic. Physicians should thus consider Q fever in the differential diagnosis of patients that present with acute fever after participating in outdoor activities.

Acute Cholangitis Caused by Boryong Strain of Orientia tsutsugamushi.

Scrub typhus present with a variety clinical manifestations caused by Orientia tsutsugamushi, it is sometimes accompanied by severe complications. The clinical course of this complication is not well clear. Herein, we first report a case with acute cholangitis and acalculous cholecystitis caused by the Boryong genotype of O. tsutsugamushi. A 82-year-old woman presented with fever and acute abdominal pain on the right upper quadrant. Initially, the patient showed an abnormality of liver enzymes of cholestatic pattern. An acute cholangitis and cholecystitis were suspected on the enhanced computed tomography (CT), and emergent endoscopic retrograde cholangiopancreatography (ERCP) performed. However, neither ERCP nor CT detected common bile duct stones or sludge. The patient's illness progressed despite bile drainage and antibiotic therapy. On the fifth day in hospital, an immunofluorescence IgG assay for O. tsutsugamushi was positive, and the patient newly developed a skin rash and an eschar lesion on the right abdomen. The polymerase chain reaction amplification of Orientia genes from blood and bile was positive, genotype of both samples was identified the Boryong type. The presentation of scrub typhus as an acute cholangitis is not reported till now. In endemic areas, scrub typhus would be considered a rare etiology of acute cholangitis.

Jejunal perforation complicating dermatomyositis.

INTRODUCTION: Small bowel perforation is rare in dermatomyositis (DM). However, it is associated with high rates of morbidity and mortality. In line with the SCARE criteria, we describe a case of jejunal perforation for a DM patient (Agha et al., 2018 [1]). CASE PRESENTATION: A 63-year-old woman had been treated for DM with high dose steroid 1 month prior to the onset of severe abdominal pain. Computed tomography (CT) revealed free air in abdominal cavity and fluid around the small bowel. She was diagnosed with small bowel perforation and underwent emergency surgery. Emergent surgery showed perforated jejunum which was resected. Pathologic reports revealed mesenteric small-vessel vasculitis with a perivascular inflammatory cell infiltration. CONCLUSION: Perforation of the small bowel for DM patients is rare. However, the early diagnosis of bowel perforation is difficult in DM because it can mimic other gastrointestinal manifestations such as ileus, ischemic colitis and peritonitis. To minimize mortality via an early diagnosis and a timely treatment, it is important to examine the patient's clinical history and employ a proper medical imaging modality such as CT even when lab findings are nonspecific and atypical.

Clinical significance of autoantibody positivity in idiopathic pulmonary fibrosis.

RATIONALE: The concept of interstitial pneumonia with autoimmune features (IPAF) was recently proposed by the American Thoracic Society. However, the clinical significance of the serologic domain of IPAF has not yet been established in idiopathic pulmonary fibrosis (IPF). OBJECTIVES: We aimed to investigate the clinical significance of autoantibody positivity in IPF. METHODS: We retrospectively reviewed the records of 512 patients diagnosed as IPF from January 2007 through March 2014. The patients were divided into two subgroups: (i) an autoantibody-positive IPF subgroup (n = 138), consisting of patients with anti-neutrophil cytoplasmic antibody (ANCA) or autoantibodies that met the criteria for the IPAF serologic domain; (ii) a lone IPF subgroup (n = 374), consisting of the rest of the IPF patients. MEASUREMENTS AND MAIN RESULTS: Autoantibody-positivity (HR 0.736, p = 0.043) was an independent risk factors for 5-year mortality on multivariable analysis in the overall IPF patients. In the autoantibody-positive IPF patients, use of glucocorticoid (not for management of acute exacerbation, HR 2.121, p = 0.019), use of immunomodulators (HR 0.310, p = 0.002), malignancy (HR 3.359, p = 0.002), baseline forced vital capacity (HR 0.974, p = 0.017), baseline diffusing capacity of the lung for carbon monoxide (HR 0.981, p = 0.041), and baseline 6-min walk test distance (HR 0.996, p = 0.002) were independent risk factors for 5-year mortality. CONCLUSIONS: Presence of ANCA or autoantibodies of the IPAF serologic domain in IPF patients is associated with better survival outcomes, and the use of immunomodulators is associated with superior survival outcomes.

Acute extensive ischemic enteritis in a young man diagnosed with wireless capsule endoscopy: a case report.

Ischemic enteritis is caused by either the interruption or significant reduction of arterial inflow to the small intestine. Risk factors are old age, diabetes mellitus and cardiovascular disease. It is very rare in young patients. We experienced a 21-year-old man with recurrent acute ischemic enteritis who was diagnosed with capsule endoscopy. He had previously taken medications for pulmonary hypertension and obstruction of both carotid arteries, and about 20 months earlier, he had been admitted due to hematochezia. Two sessions of angiography did not reveal the cause of hematochezia. At that time, capsule endoscopy showed mucosal edema and erythema in the terminal ileum, suggesting healed ischemic enteritis. The patient was admitted again due to hematochezia. Abdominal computed tomography showed focal celiac trunk stenosis and diffuse wall thickening of the small intestine, suggesting ischemic enteritis. Capsule endoscopy showed multiple active ulcers and severe hemorrhage with exudate, extending from the proximal jejunum to the terminal ileum. Using capsule endoscopy, the patient was diagnosed with acute extensive ischemic enteritis. Because endoscopic images of ischemic enteritis have rarely been reported, we report a case of a 21-year-old man who was diagnosed acute extensive ischemic enteritis with capsule endoscopy.

Comparison of the diagnostic performances of two protocols of hand perfusion scintigraphy for Raynaud's phenomenon.

OBJECTIVE: The aim of this study was to compare the diagnostic performances of two hand perfusion scintigraphy protocols for diagnosing Raynaud's phenomenon (RP). METHODS: We enrolled 130 patients who underwent hand perfusion scintigraphy for suspected RP and 40 normal controls. Of these, 66 patients (group A) and 25 normal controls underwent 99mTc-methylene diphosphonate hand perfusion scintigraphy without one-hand chilling, and the finger-to-palm ratio (FPR) was calculated. The remaining 64 patients (group B) and 15 normal controls underwent 99mTc-methylene diphosphonate hand perfusion scintigraphy with one-hand chilling, and three parameters (the chilled-to-ambient hand ratios of the first peak height, initial slope, and blood pool uptake) were calculated. RESULTS: Forty-eight and 47 patients were clinically diagnosed with RP in groups A and B, respectively. In group A, patients with RP had significantly lower FPRs compared with those without RP, and the receiver operating characteristic curve analysis showed that an FPR of 0.51 was the best cutoff value for diagnosing RP, with a sensitivity of 63% and a specificity of 83%. In group B, the three aforementioned parameters differed significantly (lower or higher) between patients with and without RP. The receiver operating characteristic curve analysis provided highly sensitive and specific results for all three parameters. The initial slope ratio showed the highest sensitivity of 87% and a specificity of 88% when using cutoff values of 0.78 and 1.25. CONCLUSION: Although both protocols for hand perfusion scintigraphy showed high specificity for diagnosing RP, the protocol with one-hand chilling showed higher diagnostic ability compared with that without one-hand chilling.