Brevundimonas vesicularis Peritonitis in a Chronic Peritoneal Dialysis Patient

Gram-negative peritonitis in chronic peritoneal dialysis patients is difficult to treat and may result in catheter loss. <i>Brevundimonas vesicularis</i> is a Gram-negative rod bacterium which rarely causes infections in humans. A 41-year-old male receiving continuous cycling peritoneal dialysis for 5 months developed culture-negative peritonitis. He failed initial empiric treatment with intraperitoneal vancomycin and levofloxacin and thereafter intravenous gentamicin. <i>B. vesicularis</i> resistant to levofloxacin was isolated from the peritoneal fluid 21 days after his initial symptoms. Despite treatment with intravenous ceftriaxone and oral amoxicillin-clavulanate, the infection persisted, which required removal of the peritoneal catheter in order to cure this infection. We describe the features of <i>B. vesicularis</i> infection in our patient and the rarely reported additional cases.

Comparing partial and continuously cycling ensemble Kalman filter data assimilation systems for convection-allowing ensemble forecast initialization

Several limited-area 80-member ensemble Kalman filter (EnKF) data assimilation systems with 15-km horizontal grid spacing were run over a computational domain spanning the conterminous United States (CONUS) for a 4-week period. One EnKF employed continuous cycling, where the prior ensemble was always the 1-h forecast initialized from the previous cycle’s analysis. In contrast, the other EnKFs used a partial cycling procedure, where limited-area states were discarded after 12 or 18 h of self-contained hourly cycles and re-initialized the next day from global model fields. “Blended” states were also constructed by combining large scales from global ensemble initial conditions (ICs) with small scales from limited-area continuously cycling EnKF analyses using a low-pass filter. Both the blended states and EnKF analysis ensembles initialized 36-h, 10-member ensemble forecasts with 3-km horizontal grid spacing. Continuously cycling EnKF analyses initialized ~1–18-h precipitation forecasts that were comparable to or somewhat better than those with partial cycling EnKF ICs. Conversely, ~18–36-h forecasts with partial cycling EnKF ICs were comparable to or better than those with unblended continuously cycling EnKF ICs. However, blended ICs yielded ~18–36-h forecasts that were statistically indistinguishable from those with partial cycling ICs. ICs that more closely resembled global analysis spectral characteristics at wavelengths > 200 km, like partial cycling and blended ICs, were associated with relatively good ~18–36-h forecasts. Ultimately, findings suggest that EnKFs employing a combination of continuous cycling and blending can potentially replace the partial cycling assimilation systems that currently initialize operational limited-area models over the CONUS without sacrificing forecast quality.

Improved Continuous-Cycling Method for PID Autotuning

An improved continuous-cycling method is proposed for the autotuning of the proportional–integral–derivative (PID) controller. The proposed method can identify the frequency response of the process at a preset phase angle without a modeling error. Moreover, it provides an exact frequency response even if a static disturbance is present. The proposed method is an improved version of the continuous-cycling method. The gain of the proportional controller in the continuous-cycling method is updated to obtain the continuous-cycling status automatically. To guarantee the preset phase angle of the frequency response, we place a phase shifter in the form of a time delay after the proportional controller. The results of simulation and experimental studies show that the proposed method can provide an exact frequency response even under static disturbance conditions and can be applied to real processes.

Dual regulation of the actin cytoskeleton by CARMIL-GAP

ABSTRACTCARMIL (Capping proteinArp2/3MyosinI Linker) proteins are multi-domain scaffold proteins that regulate actin dynamics by regulating the activity of Capping Protein (CP). Here we characterize CARMIL-GAP, aDictyosteliumCARMIL isoform that contains a ~130 residue insert that, by homology, is a GTPase activating (GAP) domain for Rho-related GTPases. Consistently, this GAP domain bindsDictyosteliumRac1a and accelerates its rate of GTP hydrolysis. CARMIL-GAP concentrates with F-actin in phagocytic cups and at the leading edge of chemotaxing cells, and cells devoid of CARMIL-GAP exhibit pronounced defects in phagocytosis and chemotactic streaming. Importantly, these defects are fully rescued by the re-expression of CARMIL-GAP. Finally, the rescue of CARMIL-GAP null cells with versions of CARMIL-GAP that lack either GAP activity or the ability to regulate CP show that while both activities contribute significantly to CARMIL-GAP function, the GAP activity plays the bigger role. Together, our results add to the growing evidence that CARMIL proteins influence actin dynamics by regulating signaling molecules as well as CP, and that the continuous cycling of Rho GTPases between their GTP and GDP bound states is often required to drive Rho-dependent biological processes.SUMMARY STATEMENTThe assembly of actin filaments supports a wide array of fundamental cellular functions, including cell migration and phagocytosis. Actin assembly is controlled by a host of regulatory proteins, with Capping Protein being one of the most important. Capping Protein is in turn regulated by the CARMIL family of proteins. Actin assembly is also controlled by signaling pathways that often converge on Rho-related GTPases like Rac1. These GTPases cycle between an active, GTP-bound state and an inactive, GDP-bound state. Guanine nucleotide exchange factors (GEFs) and guanine nucleotide activating proteins (GAPs) drive Rho-related GTPases to their GTP-bound and GDP-bound states, respectively. Here we characterized a version of CARMIL that contains within it a GAP domain for Rac1. We show that CARMILGAP supports the actin-based processes of cell migration and phagocytosis. We also show that while CARMIL-GAP’s ability to regulate Capping Protein and the nucleotide state of Rac1 are both important for its cellular functions, its ability to regulate Rac1 via its GAP domain plays the bigger role. Finally, our data support the emerging concept that the continuous cycling of Rho GTPases between their GTP-bound and GDP-bound states is often required to drive Rho-dependent biological processes.

Manic-Depressive Cycles in Bipolar Disorder: Clinical and Treatment Implications

<b><i>Introduction:</i></b> Cycle patterns of bipolar disorders (BDs) have been previously shown to be associated with clinical characteristics and response to lithium salts. Here, we evaluated the distribution of different types of manic-depressive cycles in a large sample of patients with BD. The associations between a mania-depression-interval (MDI) course and depression-mania-interval (DMI) course with sociodemographic/clinical factors were also assessed in order to define specific clinical profiles. <b><i>Methods:</i></b> In this cross-sectional study, 806 patients with BD admitted to the Psychiatric Unit of San Luigi Gonzaga Hospital in Orbassano and Molinette Hospital in Turin, Italy, were recruited. Patients were grouped according to the following course patterns: MDI, DMI, continuous cycling (CC, &#x3c;4 episodes/year without intervals), rapid cycling (RC, ≥4 episodes/year), and irregular (IRR) cycling. We compared several sociodemographic and clinical variables in an MDI versus DMI course by means of ANOVA and Pearson χ² with Bonferroni correction. <b><i>Results:</i></b> Bipolar cycles were distributed as follows: 50.2% IRR course, 31.5% MDI course, 16% DMI course, 1.2% CC, and 1% RC. Compared to DMI course, patients with an MDI course were more often men, younger, with an earlier onset, a manic polarity onset, and more lifetime compulsory admissions. They were more frequently treated with lithium and antipsychotics. Patients with a DMI course had older age at diagnosis and at first mood-stabilizer treatment and were more often misdiagnosed with a major depressive disorder. These patients were more commonly treated with anticonvulsants, and they had more frequently failed treatment trials with lithium salts in the past. <b><i>Conclusion:</i></b> This study supports the utility of classifying BD according to their course patterns. This classification holds prognostic as well as therapeutic implications.

The impact of preconditioning exercise on the vascular response to an oral glucose challenge

Exercise elicits direct benefits to insulin sensitivity but may also indirectly improve glucose uptake by hemodynamic conditioning of the vasculature. The purpose of this study was to examine the modifying effect of three different types of exercise on the vascular response to an oral glucose challenge. Twenty healthy adults (9 women, 11 men; 23±3 years old) completed a standard oral glucose tolerance test (OGTT) at rest, as well as 1.5 hours after moderate continuous cycling exercise (30 min; 65% V̇O2peak), high intensity interval cycling exercise (10x1 min at 90% heart rate peak), and lower-load higher-repetition resistance exercise (25-35 repetitions/set, 3 sets). Brachial and superficial femoral artery blood flow, conductance, and oscillatory shear index were measured throughout the OGTT. Regardless of rested state or exercise preconditioning, the OGTT induced reductions in brachial artery blood flow and conductance (p<0.001), and transient increases in brachial and superficial femoral artery oscillatory shear index and retrograde blood flow (p<0.01). Continuous cycling and resistance exercise were followed with a small degree of protection against prolonged periods of oscillatory flow. Our findings imply transient peripheral vasoconstriction and decreased limb blood flow during a standard OGTT, for which prior exercise was unable to prevent in healthy adults. NOVELTY BULLETS • We investigated the impact of continuous, interval, and resistance exercise on the hemodynamic response to an oral glucose tolerance test (OGTT). • Our findings suggest decreased upper-limb blood flow during an OGTT is not prevented by prior exercise in healthy adults.

Forty years of peritoneal dialysis Listeria peritonitis: Case and review

Infections with Listeria monocytogenes (LM) are very uncommon and severe especially in immunocompromised people. We report a continuous cycling peritoneal dialysis (CCPD) patient who presented initially disseminated listeriosis with peritonitis. He was successfully treated with intraperitoneal and intravenous ampicillin but died unfortunately from a cardiorespiratory arrest due to food inhalation. It is the 20th case of such peritonitis mentioned among PD patients and the first reported in Belgium. This case illustrates the importance of a systematic approach to get quick diagnosis and effective antibiotic readjustment. Empiric therapy is not effective on Listeria which is naturally resistant to cephalosporins and poorly sensitive to vancomycin. Ampicillin is the first-line antibiotic. In case of penicillin allergy, trimethoprim–sulfamethoxazole or erythromycin can be used successfully. Identification of LM serotype has a prognostic value. PD educative programmes should recommend to avoid unpasteurized dairy products to prevent listeriosis.

From cancer to rejuvenation: incomplete regeneration as the missing link (part II: rejuvenation circle)

In the first part of our study, we substantiated that the embryonic reontogenesis and malignant growth (disintegrating growth) pathways are the same, but occur at different stages of ontogenesis, this mechanism is carried out in opposite directions. Cancer has been shown to be epigenetic-blocked redifferentiation and unfinished somatic embryogenesis. We formulated that only this approach of aging elimination has real prospects for a future that is fraught with cancer, as we will be able to convert this risk into a rejuvenation process through the continuous cycling of cell dedifferentiation–differentiation processes (permanent remorphogenesis). Here, we continue to develop the idea of looped ontogenesis and formulate the concept of the rejuvenation circle.