Transgenic rats expressing dominant negative BMAL1 showed circadian clock amplitude reduction and rapid recovery from jet lag.

The circadian rhythms are endogenous rhythms of about 24 h, and are driven by the circadian clock. The clock centre locates in the suprachiasmatic nucleus. Light signals from the retina shift the circadian rhythm in the suprachiasmatic nucleus, but there is a robust part of the suprachiasmatic nucleus that causes jet lag after an abrupt shift of the environmental lighting condition. To examine the effect of attenuated circadian rhythm on the duration of jet lag, we established a transgenic rat expressing BMAL1 dominant negative form under control by mouse Prnp-based transcriptional regulation cassette [BMAL1 DN (+)]. The transgenic rats became active earlier than controls, just after light offset. Compared to control rats, BMAL1 DN (+) rats showed smaller circadian rhythm amplitudes in both behavioural and Per2 promoter driven luciferase activity rhythms. A light pulse during the night resulted in a larger phase shift of behavioural rhythm. Furthermore, at an abrupt shift of the light-dark cycle, BMAL1 DN (+) rat showed faster entrainment to the new light-dark cycle compared to controls. The circadian rhythm has been regarded as a limit cycle phenomenon, and our results support the hypothesis that modification of the amplitude of the circadian limit cycle leads to alteration in the length of the phase shift.

Vagococcus fluvialis as a causative pathogen of bloodstream and decubitus ulcer infection: Case report and systematic review of the literature.

BACKGROUND: Vagococcal infections are uncommon in humans; there are limited studies on the clinical manifestations, the optimal methods for identifications, and antimicrobial susceptibility testing for vagococcal infections. Here, we have reported a case of Vagococcus fluvialis-induced bacteremia and decubitus ulcer and have systematically reviewed other reported Vagococcus infections. CASE PRESENTATION: A 74-year-old man presented to our emergency department with muscle weakness on his left extremities, dysarthria, and altered mental status along with fever for the past 4 days. Physical examination revealed a decubitus ulcer with foul smelling and yellowish exudative pus on his left chest wall and abdomen, forearm, thigh, and lower leg. He was empirically treated with 2.25 mg of piperacillin/tazobactam every 8 hours and 0.5 g of vancomycin every 24 hours intravenously (IV) for his decubitus ulcer. Vagococcus fluvialis was detected in both aerobic and anaerobic blood cultures (upon admission) using the VITEC 2 GP ID card (bioMérieux) and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). We continued the mentioned IV antimicrobial therapies for 4 weeks following which the patient was transferred to a long-term care facility for further rehabilitation. CONCLUSIONS: To our best knowledge, this is the first literature review of Vagococcus infections in humans. Since it is challenging to distinguish Vagococcus from Enterococcus by a conventional method due to the similarity of its biochemical properties to those of Enterococcus, based on our literature review, 16S rRNA sequencing or analysis of bacterial protein profile using MALDI-TOF MS may be useful for the precise identification.

Disseminated nocardiosis due to Nocardia terpenica.

We report the first case of disseminated nocardiosis due to trimethoprim/sulfamethoxazole-resistant Nocardia terpenica successfully treated with meropenem and clarithromycin. The patient travelled to Japan from Australia via Southeast Asia, which led to differential diagnoses of multiple lung nodules including miliary tuberculosis and melioidosis as well as nocardiosis. Because of variety of susceptibility depending on the Nocardia species, clinicians need to confirm the species and investigate its susceptibility.

COVID-19 in 2 Persons with Mild Upper Respiratory Tract Symptoms on a Cruise Ship, Japan.

We describe 2 cases of coronavirus disease in patients with mild upper respiratory symptoms. Both patients worked on a cruise ship quarantined off the coast of Japan. One patient had persistent, low-grade upper respiratory tract symptoms without fever. The other patient had rapid symptom cessation but persistent viral RNA detection.

Infected aortic aneurysm caused by Helicobacter cinaedi: case series and systematic review of the literature.

BACKGROUND: Helicobacter cinaedi is rarely identified as a cause of infected aneurysms; however, the number of reported cases has been increasing over several decades, especially in Japan. We report three cases of aortic aneurysm infected by H. cinaedi that were successfully treated using meropenem plus surgical stent graft replacement or intravascular stenting. Furthermore, we performed a systematic review of the literature regarding aortic aneurysm infected by H. cinaedi. CASE PRESENTATION: We present three rare cases of infected aneurysm caused by H. cinaedi in adults. Blood and tissue cultures and 16S rRNA gene sequencing were used for diagnosis. Two patients underwent urgent surgical stent graft replacement, and the other patient underwent intravascular stenting. All three cases were treated successfully with intravenous meropenem for 4 to 6 weeks. CONCLUSIONS: These cases suggest that although aneurysms infected by H. cinaedi are rare, clinicians should be aware of H. cinaedi as a potential causative pathogen, even in immunocompetent patients. Prolonged incubation periods for blood cultures are necessary for the accurate detection of H. cinaedi.

Aspergillus meningitis in a patient with chronic lymphocytic leukemia.

Central nervous system aspergillosis is relatively rare and difficult to diagnose. Here, we report a case of 90-year-old man with chronic lymphocytic leukemia who presented with a month-long gradually worsening headache followed by 3 days of low-grade fever associated with altered mental status. Aspergillus meningitis diagnosed using Aspergillus galactomannan antigen in the cerebrospinal fluid and treated with voriconazole. Delayed diagnosis and treatment of Aspergillus meningitis is typically associated with high mortality; therefore, it is imperative to include this disease in the differential diagnoses of subacute meningitis.

Clinical and Molecular Characteristics of Klebsiella pneumoniae Isolates Causing Bloodstream Infections in Japan: Occurrence of Hypervirulent Infections in Health Care.

Although hypervirulent Klebsiella pneumoniae (hvKp) has been associated with severe community-acquired infections that occur among relatively healthy individuals, information about hvKp infections in health care settings remains limited. Here, we systematically analyzed the clinical and molecular characteristics of K. pneumoniae isolates causing bloodstream infections in a cross-sectional study. Clinical characteristics of K. pneumoniae bloodstream infections from hospitals across Japan were analyzed by a review of the medical records. Whole-genome sequencing of the causative isolates was performed. Bacterial species were confirmed and hvKp were identified using whole-genome sequencing data. Clinical characteristics of hvKp infections were compared with those of non-hvKp infections by bivariate analyses. Of 140 cases of K. pneumoniae bloodstream infections, 26 cases (18.6%) were caused by various clones of hvKp defined by the carriage of cardinal virulence genes. Molecular identification revealed that 24 (17.1%) and 14 (10%) cases were caused by Klebsiella variicola and Klebsiella quasipneumoniae, respectively. Patients with hvKp infections had higher proportions of diabetes mellitus (risk ratio [RR], 1.75; 95% confidence interval [CI], 1.05 to 2.94), and their infections had significantly higher propensity to involve pneumonia (RR, 5.85; 95% CI, 1.39 to 24.6), liver abscess (RR, 5.85; 95% CI, 1.39 to 24.6), and disseminated infections (RR, 6.58; 95% CI, 1.16 to 37.4) than infections by other isolates. More than one-half of hvKp infections were health care associated or hospital acquired, and a probable event of health care-associated transmission of hvKp was documented. hvKp isolates, which are significantly associated with severe and disseminated infections, are frequently involved in health care-associated and hospital-acquired infections in Japan.

Endoscopic findings and lesion distribution in amebic colitis.

A retrospective cohort study was conducted in 55 symptomatic patients with amebic colitis that visited at St. Luke's International Hospital and Mie University Hospital from 1994 through 2013. To diagnose amebic colitis, 40 patients underwent total colonoscopy within 1 week after hospital visiting and before receiving any treatment. The percentage of characteristic endoscopic findings of amebic colitis including discrete ulcers or erosions with white or yellow exudates were 0% in terminal ileum, 93% in cecum, 28% in ascending, 25% in transverse, 15% in descending, 20% in sigmoid colon and 45% in rectum. The rectal lesions in 55% of patients with amebic colitis were nonspecific. The trophozoite identification rate by direct smear of intestinal tract washings performed during colonoscopy was 88%. The protozoan identification rate was 70% in biopsy specimens taken from the periphery of the characteristic discrete ulcers. Total colonoscopy should be considered for the diagnosis of amebic colitis.

Regional circadian period difference in the suprachiasmatic nucleus of the mammalian circadian center.

The suprachiasmatic nucleus (SCN) is the mammalian circadian rhythm center. Individual oscillating neurons have different endogenous circadian periods, but they are usually synchronized by an intercellular coupling mechanism. The differences in the period of each oscillating neuron have been extensively studied; however, the clustering of oscillators with similar periods has not been reported. In the present study, we artificially disrupted the intercellular coupling among oscillating neurons in the SCN and observed regional differences in the periods of the oscillating small-latticed regions of the SCN using a transgenic rat carrying a luciferase reporter gene driven by regulatory elements from a per2 clock gene (Per2::dluc rat). The analysis divided the SCN into two regions--aregion with periods shorter than 24 h (short-period region, SPR) and another with periods longer than 24 h (long-period region, LPR). The SPR was located in the smaller medial region of the dorsal SCN, whereas the LPR occupied the remaining larger region. We also found that slices containing the medial region of the SCN generated shorter circadian periods than slices that contained the lateral region of the SCN. Interestingly, the SPR corresponded well with the region where the SCN phase wave is generated. We numerically simulated the relationship between the SPR and a large LPR. A mathematical model of the SCN based on our findings faithfully reproduced the kinetics of the oscillators in the SCN in synchronized conditions, assuming the existence of clustered short-period oscillators.

[A study for candidemia during the six year period from 1993 to 1999 in St. Luke's International Hospital].

There were 71 patients with candidemia in our hospital from November 1, 1993 to October 31, 1999. We investigated the 59 patients from isolated species, route of infection, underlying disorders, risk factors, complications, treatment and prognosis.Candida albicans was the most commonly isolated species (52%), followed by Candida tropicalis (11%). Eighty eight percent of the patients developed candidemia from central venous catheter related infections. The risk factors to candidemia included keeping the catheter in place for more than 5 days, gastrointestinal tract malignancies, postoperative state of gastrointestinal tract surgery, administration of broad-spectrum or combination antibiotics for more than 5 days, and under corticosteroid therapy. About half of the patients (47%) had complications, including endophthalmitis (19 patients, 32%), septic shock (12 patients, 20 %). Mortality rate associated with candidemia was 46%. Mortality rate was lower in 20 patients who were treated with amphotericin B (40%) than in 34 patients treated with only fluconazole (50%), but it was not statistically significant. In order to make an early diagnosis of candidemia, taking blood cultures and ophthalmologic examinations are essential, especially for patients who have those risk factors to candidemia mentioned above. If the patient was suspected of having catheter related infection, the catheter should be removed quickly and the catheter tip should be cultured. Once candidemia is found, ophthalmologic examination and systemic antifungal therapy are needed. Antifungal therapy with Amphotericin B should be used for patients with severe candidemia or with candide-

[A case of cysticercosis with multiple intracerebral and intramuscular nodular lesions].

A 47-year-old Chinese woman with no significant medical history admitted for sudden-onset seizures and transient right homonymous hemianopsia had moved from China to Japan 4 years previously. Contrast brain computed tomography (CT) showed multiple calcified nodular lesions with surrounding edema, one in the left parietal lobe being likely responsible for her visual symptoms. After admission, two painful intramuscular nodular lesions were found in her left lower limb. Histopathologically biopsy specimens from these lesions were not diagnostic. Serum antibody testing (ELISA) for Taenia solium, however, was positive, yielding a diagnosis of (neuro) cysticercosis. The woman responded well to albendazole and prednisolone treatment. In the two years since discharge, she has not developed any new symptoms or seizure recurrence. With increasing global travel, clinicians must thus consider the possibility of neurocysticercosis in cases of nodular brain lesions in subjects from areas where Taenia solium remains endemic.

Staphylococcus Aureus Bacteremia Due to Central Venous Catheter Infection: A Clinical Comparison of Infections Caused by Methicillin-Resistant and Methicillin-Susceptible Strains.

OBJECTIVES: Staphylococcus aureus bacteremia has a mortality rate of 20-40% and is mainly caused by central venous catheter (CVC) infection. We aimed to investigate differences between patients with methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) bacteremia due to CVC infection. METHODS: This retrospective study, of data collected between August 2004 and March 2016 at a single Tokyo hospital, compared the clinical background characteristics, complications, and 60-day mortality rates with positive peripheral blood cultures and positive semiquantitative cultures. MRSA carrier is defined as those with a history of MRSA detection by skin, urine, or sputum culture. RESULTS: The median ages for the 17 MRSA and 19 MSSA patients were 72 and 55 years, respectively (P < 0.01). The occurrences of baseline disease (MRSA vs. MSSA) were 59% vs. 16% (P = 0.01), respectively, while those of complications, including septic shock, were 48% vs. 16% (P = 0.07), respectively. Catheter placement duration, time from fever onset to CVC removal, and time from fever onset to antimicrobial therapy initiation were similar in both groups. Sixty-day mortality rates were 35% and 5.3% (P = 0.04) in the MRSA and MSSA groups, respectively. CONCLUSION: MRSA carriers and older patients were at higher risks of CVC infection than MSSA bacteremia patients. Patients with MRSA bacteremia had higher septic shock and 60-day mortality rates despite appropriate antimicrobial therapy.

Effectiveness of daptomycin against infective endocarditis caused by highly penicillin-resistant viridans group streptococci.

Penicillin-resistant viridans group streptococci (VGS) infections are an emerging issue in infectious diseases. Here, we present a case of mitral valve infective endocarditis caused by highly penicillin-resistant VGS (minimum inhibitory concentration >4 µg/mL), which was successfully treated with daptomycin. Although the clinical efficacy of daptomycin has not been established, it can be an alternative for the treatment of highly resistant VGS endocarditis.

Acquired Hemophilia A Presenting with Infectious Aortic Aneurysms Due to an Underlying Helicobacter cinaedi Infection.

Acquired hemophilia A (AHA) is a bleeding disorder caused by the acquired appearance of inhibitor for factor VIII. Approximately half of all patients with AHA have some type of underlying disease. We herein report the case of a 72-year-old Japanese man with AHA who presented with infectious aortic aneurysms due to an underlying Helicobacter cinaedi infection. To our knowledge, this is the first report of AHA triggered by a bacterial infection; however, there may be similar cases that remain undiagnosed because this pathogen is difficult to identify. Clinicians should consider the possibility of H. cinaedi as a causative pathogen in patients presenting with a fever of unknown origin.

[A case of severe leptospirosis infection (Weil's disease) in Tokyo].

We report a case of severe leptospirosis infection (Weil's disease) in Tokyo. A 54-year-old man admitted on September 14, 2006, for a 5-day inability to walk due to severe progressive bilateral leg pain, shoulder pain, and fever exhibited jaundice, conjunctival suffusion, hypoxia, and grasping pain in the bilateral leg muscles. Laboratory findings showed severe liver damage, renal failure, leukocytosis, anemia, thrombocytopenia, elevated CRP, hyponatremia, and hypokalemia. Chest X-ray imaging showed interstitial infiltrates in the bilateral lung fields. After cefepime was initiated, he developed chills, fever, and hypotension due to Jarisch-Herxheimer reaction, necessitating respiratory support. Pulmonary hemorrhaging was also found. On hospital day 2, a urine polymerase chain reaction test for leptospira proved positive for the same base sequence as part of the leptospira gene. A microscopic agglutination test showed elevated antibody titers against Leptospira interrogans. Based on a diagnosis of leptospirosis, the man was treated with 2g per day of ceftriaxione for 2 weeks and recovered fully. The leptospira strain was isolated from rodents captured at his home, and we identified the same base sequence as from his urine sample. Reports shows, leptospirosis in Japan have decreased recently, but, as this case can still be seen even in Tokyo, and diagnosticians should maintain an awareness of possible significance in patients with typical findings for this disease.

Infective endocarditis caused by Salmonella enteritidis in a dialysis patient: a case report and literature review.

BACKGROUND: Infective endocarditis is significantly more common in haemodialysis patients as compared with the general population, the causative pathogen is generally Staphylococcus aureus; there have been no previously reported cases of infective endocarditis caused by a Salmonella species in haemodialysis patients. CASE PRESENTATION: We report the case of a 68 year-old woman on haemodialysis who developed infective endocarditis as a result of Salmonella enteritidis. Although we treated the patient with ceftriaxone combined with ciprofloxacin, infective endocarditis was not detected early enough and unfortunately developed into cerebral septic emboli, which ultimately resulted in death. CONCLUSION: Although there are several reports that Salmonella endocarditis without cardiac failure can be successfully treated with antibiotics alone, early surgical intervention is essential for some cases to prevent life-threatening complications. Transesophageal echocardiography should be performed in any patient with high clinical suspicion of infective endocarditis. To the best of our knowledge, this is the first case-report of Salmonella endocarditis in a haemodialysis patient.

Calculus pyelonephritis associated with ureterocutaneostomy.

A 79-year-old woman with a history of total hysterectomy for cervical cancer with ureterocutaneostomy presented with high fever. She had tenderness and a hard lump around the ureterocutaneostomy site. Computed tomography scan revealed 1.5 cm ureteral calculus in ureterocutaneous fistula (Fig. 1A) associated with bilateral hydronephrosis (Fig. 1B) and we performed a transureteral stent insertion. Blood culture grew methicillin-sensitive Staphylococcus aureus (MSSA), Haemophilus parainfluenzae, Veillonella species and Bacteroides fragilis and urine culture revealed Escherichia coli, MSSA, and Enterococcus faecalis. The patient's clinical signs and symptoms gradually improved with ampicillin/sulbactam. Patients with urinary diversions including ureterocutaneostomy and iliac conduits are at increased risk of urolithiasis (1), which can cause sepsis, pyelonephritis, and renal insufficiency (2). Since most patients become colonized with a multitude of bacteria including Enterobacteriaceae and skin flora such as Staphylococcus aureus and Streptococcus spp., we should empirically treat with broad-spectrum antimicrobials until the culture results are available. Early diagnosis and urological intervention are required because it can be life-threatening with delayed treatment.

Listeria monocytogenes meningitis.

Tumbling motility is one of the useful characteristics of Listeria monocytogenes. This can be helpful to identify the causative pathogen along with Gram staining before the confirmatory microbiological examination.