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.

The suprachiasmatic nucleus is the master circadian clock and resets the peripheral clocks via various pathways. Glucocorticoids and daily feeding are major time cues for entraining most peripheral clocks. However, recent studies have suggested that the dominant timing factor differs among organs and tissues. In our current study, we reveal differences in the entrainment properties of the peripheral clocks in the liver, kidney, and lung through restricted feeding (RF) and antiphasic corticosterone (CORT) injections in adrenalectomized rats. The peripheral clocks in the kidney and lung were found to be entrained by a daily stimulus from CORT administration, irrespective of the meal time. In contrast, the liver clock was observed to be entrained by an RF regimen, even if daily CORT injections were given at antiphase. These results indicate that glucocorticoids are a strong zeitgeber that overcomes other entrainment factors regulating the peripheral oscillators in the kidney and lung and that RF is a dominant mediator of the entrainment ability of the circadian clock in the liver. (Endocrinology 153: 2277-2286, 2012) M ost living organisms have developed internal clock mechanisms that generate precise rhythms around a 24-h cycle. One such system, termed the circadian clock, governs daily variations in physiology and behavior. In mammals, the suprachiasmatic nucleus (SCN) is the center of the circadian clock and resides in the hypothalamus (1). The molecular oscillator in the SCN consists of interacting positive and negative transcription/translation feedback loops (2-4). The transcriptional activators CLOCK and BMAL1 form heterodimers and stimulate the transcription of other clock genes, such as the Period (Per) genes (Per1, Per2, and Per3), the Cryptochromes (Cry) (Cry1 and Cry2), retinoid-related orphan receptors (ROR) (ROR␣, ROR␤, and ROR␥) and Rev-erbes (Rev-erb␣ and Rev-erb␤) that bind to the E-box response elements in the promoter regions of these genes. Accumulated PER and CRY proteins form a complex that represses the transcriptional activity of the CLOCK/BMAL1 heterodimer. The ROR transcriptional activators and REV-ERB repressors control the transcriptional regulation of Clock and Bmal1 through their binding to the REV response element (RRE). This autoregulatory loop generates gene expression oscillations of approximately 24 h. In addition, the mammalian SCN can adapt to environmental changes in day/night cycles. Light information from the retinas is delivered to the SCN via the retino-hypothalamic tract and is the most effective time cue for the central clock. Nocturnal light induces the Per1 and Per2 genes, which leads to a resetting of the circadian clock in the SCN (5).The molecular circadian clock operates not only in the SCN but also in peripheral organs and tissues (6, 7). The peripheral clocks are entrained by the central circadian clock in the SCN and express overt circadian rhythms during physiological events (8, 9). Hence, it is commonly assumed that the mammalian circadian system is a complex h...

We report a case of severe acute respiratory syndrome coronavirus 2 and Legionella co-infection manifesting as pneumonia with gastrointestinal symptoms. The case highlights the importance of differential diagnosis during the COVID-19 pandemic, so we do not miss the opportunity to diagnose other treatable causes of disease with similar symptoms.

We postulate that the mechanisms leading to the development of GEFV functional anomalies in men are different from those in women. Future evaluations of EP-GERD should also observe GEFV function.