Reliable Initial Trauma CT Findings of Supraclavicular Brachial Plexus Injury in Patients Sustaining Blunt Injuries.

BACKGROUND AND PURPOSE: Traumatic brachial plexus injuries are uncommon but can be debilitating. Early diagnosis is critical. Most patients undergo CT after trauma. We sought to identify correlative CT findings of supraclavicular brachial plexus injuries to discern who may require further evaluation with MR imaging and to measure multireviewer performance for their interpretations. MATERIALS AND METHODS: We identified all MR imaging examinations of the brachial plexus from our institution from January 2010 to January 2021 and included those performed for trauma. We excluded patients with penetrating or infraclavicular injuries and without preceding CTA of the neck or CT of the cervical spine. The cohort of 36 cases and 50 controls remained for analysis and were assessed for 6 findings: scalene muscle edema/enlargement, interscalene fat pad effacement, first rib fracture, cervical spine lateral mass/transverse process fracture, extra-axial cervical spinal hemorrhage, and cervical spinal cord eccentricity, forming a reference key. A resident physician and 2 neuroradiologists (blinded to the MR imaging) independently reviewed each CT scan for these findings. We measured agreement (Cohen κ) between observers and against the reference key. RESULTS: Interscalene fat pad effacement (sensitivity, specificity, 94.44%, 90.00%; OR = 130.33; P < .001) and scalene muscle edema/enlargement (sensitivity, specificity, 94.44%, 88.00%; OR = 153.00; P < .001) correlated significantly with brachial plexus injury. Agreement between observers and the key was almost perfect for those findings and fractures (pooled κ ≥ 0.84; P < .001). Agreement between observers was variable (κ = 0.48-0.97; P < .001). CONCLUSIONS: CT can accurately predict brachial plexus injuries, potentially enabling earlier definitive evaluation. High interobserver agreement suggests that findings are consistently learned and applied.

Reduction in femoral neck and total hip bone mineral density following hospitalisation for diabetes-related foot ulceration.

Management of diabetes-related foot ulceration (DFU) includes pressure offloading resulting in a period of reduced activity. The metabolic effects of this are unknown. This study aims to investigate changes in bone mineral density (BMD) and body composition 12 weeks after hospitalisation for DFU. A longitudinal, prospective, observational study of 22 people hospitalised for DFU was conducted. Total body, lumbar spine, hip and forearm BMD, and total lean and fat mass were measured by dual-energy X-ray absorptiometry (DXA) during and 12 weeks after hospitalisation for DFU. Significant losses in total hip BMD of the ipsilateral limb (- 1.7%, p < 0.001), total hip BMD of the contralateral limb (- 1.4%, p = 0.005), femoral neck BMD of the ipsilateral limb (- 2.8%, p < 0.001) and femoral neck BMD of the contralateral limb (- 2.2%, p = 0.008) were observed after 12 weeks. Lumbar spine and forearm BMD were unchanged. HbA1c improved from 75 mmol/mol (9.2%) to 64 mmol/mol (8.0%) (p = 0.002). No significant changes to lean and fat mass were demonstrated. Total hip and femoral neck BMD decreased bilaterally 12 weeks after hospitalisation for DFU. Future research is required to confirm the persistence and clinical implications of these losses.

Management of diabetes-related foot disease in the outpatient setting during the COVID-19 pandemic.

The use of telephone and/or video consultation in routine management of acute diabetes-related foot disease (DFD) before the coronavirus disease 2019 (COVID-19) pandemic at a tertiary hospital is unprecedented. In March 2020, the Diabetes Feet Australia (DFA) released a national guideline to inform DFD management during the COVID-19 pandemic. The present study aimed to describe the adherence to the DFA guideline of managing acute DFD using telephone and/or video consultation at a Western Australian tertiary hospital during this period. We found >80% adherence rate to the DFA guideline and the management of active DFD using telephone and/or video consultations was feasible and acceptable in carefully selected patients.

Design of target irradiation and diagnostic chamber to study ps-laser generated plasma as a source of singly charged ions for external injection into an electron beam ion source.

High repetition-rate (∼10 kHz) ps-lasers are becoming available on the market with reasonable cost and may offer several advantages compared to ns-lasers by generating nearly continuous beams of singly charged ions appropriate for the "slow" injection mode into the Electron Beam Ion Source (EBIS). To evaluate these advantages, we will perform studies of a ps-laser generated plasma using a laser with a pulse duration of 8 ps and energy up to 5 mJ per pulse. A vacuum chamber equipped with a 3D target positioner, a focusing lens, and a Faraday Cup has been designed and built for this study. Lens-to-target distance variations have been measured using a laser tracker over the whole range of horizontal and vertical translation for all five targets we will use. The variations were found to be within ±150 µm. This degree of "target flatness" should be acceptable for our experimental conditions. Ion currents and ion pulse durations of various elements (from Al to Ta) will be measured for different target irradiation conditions (focal spot size and laser pulse energy). The results obtained will allow us to specify all parameters and geometry of a laser ion source based on a ps-laser to provide external ion injection into the relativistic heavy ion collider EBIS.

Development of highly efficient NEG pumping system for EBIS.

Ultrahigh vacuum inside the ion trap volume is crucial for stable and reliable operation of an Electron Beam Ion Source (EBIS). We have developed and tested a compact linear pumping system based on the ZAO Non-Evaporable Getter (NEG) module with high pumping speed and enhanced sorption capacity for all active gases. Due to its minimal transverse dimensions, the system can be mounted adjacent to the ion trap inside a superconducting solenoid bore and will provide a pumping speed of the order of 1000 l/s for all active gases in that area. An externally supplied current (100 A DC) is used to heat the ZAO NEG up to 650 °C for more than 1 h, which is required for pump activation and/or reactivation cycles. The pumping system is being developed for use in the Extended EBIS Upgrade which is presently in progress at BNL. The design of the system and results of multiple tests are presented and discussed.

Risk detection in patients with obstructive sleep apnea syndrome based on cardiovascular time series analysis.

Obstructive sleep apnea represents the most common form of sleep-disordered breathing and has a high prevalence in patients with cardiovascular disease. Disturbed sleep is a potential risk factor for cardiovascular disorders such as arterial hypertension, cardiac ischemia, sudden cardiac death, and stroke. In this study we investigated polysomnographic records and analyzed the ECG, plethysmogram, respiration and SpO2 time series during wakefulness (WK), NREM, and REM sleep stages applying variability and coupling analyses methods. We enrolled 55 patients with obstructive sleep apnea syndrome (OSAS) and 29 healthy control subjects (CON: 45.9±14.9 years, 21 male) in this study. OSAS patients were subdivided into a low- and high-risk group (LR: 50.8±14.1 years, n=29, 21 male; HR: 57.2±13.4 years, n=26, 19 male) based on the Apnea-Hypopnea Index (AHI) (CON: 0-5 AHI, LR: 5-15 AHI, HR: >15 AHI). We could demonstrate the presence of an altered autonomic function in OSAS patients, differing from healthy controls. This altered autonomic function was mainly based on heart rate-, respiratory-, SpO2- and plethysmogram variability and their couplings. The discriminant analysis showed that the optimal set consisting of two autonomic indices revealed a high classification power (ACC=86.7%, AUC=90.3%, SENS=89.5% and SPEC=84.6%) when comparing low-risk and high-risk OSAS patients during WK. These results were slightly improved when analyzing REM sleep stages. Based on these results it seems to be possible to perform optimal risk stratification for OSAS patients based on autonomic indices. Based on our findings it is possible to differentiate between high-risk OSAS patient and low-risk OSAS patient at an early stage and in a promising manner allowing to set up therapy strategies for those patients in an early stage.

Early Infectious Diseases Specialty Intervention Is Associated With Shorter Hospital Stays and Lower Readmission Rates: A Retrospective Cohort Study.

Background: Intervention by infectious diseases (ID) physicians improves outcomes for inpatients in Medicare, but patients with other insurance types could fare differently. We assessed whether ID involvement leads to better outcomes among privately insured patients under age 65 years hospitalized with common infections. Methods: We performed a retrospective analysis of administrative claims data from community hospital and postdischarge ambulatory care. Patients were privately insured individuals less than 65 years old with an acute-care stay in 2014 for selected infections, classed as having early (by day 3) or late (after day 3) ID intervention, or none. Key outcomes were mortality, cost, length of the index stay, readmission rate, mortality, and total cost of care over the first 30 days after discharge. Results: Patients managed with early ID involvement had shorter length of stay, lower spending, and lower mortality in the index stay than those patients managed without ID involvement. Relative to late, early ID involvement was associated with shorter length of stay and lower cost. Individuals with early ID intervention during hospitalization had fewer readmissions and lower healthcare payments after discharge. Relative to late, those with early ID intervention experienced lower readmission, lower spending, and lower mortality. Conclusions: Among privately insured patients less than 65 years old, treated in a hospital, early intervention with an ID physician was associated with lower mortality rate and shorter length of stay. Patients who received early ID intervention during their hospital stay were less likely to be readmitted after discharge and had lower total healthcare spending.

A reference high-pressure CO2 adsorption isotherm for ammonium ZSM-5 zeolite: results of an interlaboratory study.

This paper reports the results of an international interlaboratory study led by the National Institute of Standards and Technology (NIST) on the measurement of high-pressure surface excess carbon dioxide adsorption isotherms on NIST Reference Material RM 8852 (ammonium ZSM-5 zeolite), at 293.15 K (20 °C) from 1 kPa up to 4.5 MPa. Eleven laboratories participated in this exercise and, for the first time, high-pressure adsorption reference data are reported using a reference material. An empirical reference equation n e x = d ( 1 + exp [ - ln ( P ) + a / b ] ) c , [n ex -surface excess uptake (mmol/g), P-equilibrium pressure (MPa), a = -6.22, b = 1.97, c = 4.73, and d = 3.87] along with the 95% uncertainty interval (U k = 2 = 0.075 mmol/g) were determined for the reference isotherm using a Bayesian, Markov Chain Monte Carlo method. Together, this zeolitic reference material and the associated adsorption data provide a means for laboratories to test and validate high-pressure adsorption equipment and measurements. Recommendations are provided for measuring reliable high-pressure adsorption isotherms using this material, including activation procedures, data processing methods to determine surface excess uptake, and the appropriate equation of state to be used.

PD-1 expression on CD8+ T cells regulates their differentiation within lung allografts and is critical for tolerance induction.

Immunological requirements for rejection and tolerance induction differ between various organs. While memory CD8+ T cells are considered a barrier to immunosuppression-mediated acceptance of most tissues and organs, tolerance induction after lung transplantation is critically dependent on central memory CD8+ T lymphocytes. Here we demonstrate that costimulation blockade-mediated tolerance after lung transplantation is dependent on programmed cell death 1 (PD-1) expression on CD8+ T cells. In the absence of PD-1 expression, CD8+ T cells form prolonged interactions with graft-infiltrating CD11c+ cells; their differentiation is skewed towards an effector memory phenotype and grafts are rejected acutely. These findings extend the notion that requirements for tolerance induction after lung transplantation differ from other organs. Thus, immunosuppressive strategies for lung transplant recipients need to be tailored based on the unique immunological properties of this organ.

The role of C4d deposition in the diagnosis of antibody-mediated rejection after lung transplantation.

Antibody-mediated rejection (AMR) is an increasingly recognized form of lung rejection. C4d deposition has been an inconsistent finding in previous reports and its role in the diagnosis has been controversial. We conducted a retrospective single-center study to characterize cases of C4d-negative probable AMR and to compare these to cases of definite (C4d-positive) AMR. We identified 73 cases of AMR: 28 (38%) were C4d-positive and 45 (62%) were C4d-negative. The two groups had a similar clinical presentation, and although more patients in the C4d-positive group had neutrophilic capillaritis (54% vs. 29%, P = .035), there was no significant difference in the presence of other histologic findings. Despite aggressive antibody-depleting therapy, 19 of 73 (26%) patients in the overall cohort died within 30 days, but there was no significant difference in freedom from chronic lung allograft dysfunction (CLAD) or survival between the two groups. We conclude that AMR may cause allograft failure, but that the diagnosis requires a multidisciplinary approach and a high index of suspicion. C4d deposition does not appear to be a necessary criterion for the diagnosis, and although some cases may respond initially to therapy, there is a high incidence of CLAD and poor survival after AMR.

Safety, tolerability, pharmacokinetics and pharmacodynamics of AZP-531, a first-in-class analogue of unacylated ghrelin, in healthy and overweight/obese subjects and subjects with type 2 diabetes.

AIM: To explore the safety, pharmacokinetics and pharmacodynamics in humans of the unacylated ghrelin analogue AZP-531, designed to improve glycaemic control and reduce weight. METHODS: Assessments, including glucose measurements, were performed in a three-part randomized study. In Part A, healthy subjects [n = 44, age 18-50 years, body mass index (BMI) 20-28 kg/m(2) ] received a single subcutaneous dose of 0.3, 3, 15, 30, 60 or 120 µg/kg AZP-531 or placebo. In Part B, overweight/obese subjects (n = 32, age 18-65 years, BMI 28-38 kg/m(2) ) and in Part C, patients with type 2 diabetes [T2D; n = 36, age 18-65 years, BMI 20-40 kg/m(2) , glycated haemoglobin (HbA1c) 7-10%] received AZP-531 or placebo for 14 days (daily doses of 3, 15, 30 or 60 µg/kg and 15, 2 × 30 or 60 µg/kg, respectively). RESULTS: AZP-531 was well tolerated. Single- and multiple-dose pharmokinetic variables were similar. Maximum AZP-531 concentrations were typically reached at 1 h post-dose. Observed maximum concentration (Cmax ) and area under the curve were dose-proportional. The mean terminal half-life (t1/2 ) was 2-3 h. In Part B, AZP-531 doses of ≥15 µg/kg significantly improved glucose concentrations, without increasing insulin levels, suggesting an insulin-sensitizing effect. AZP-531 decreased mean body weight by 2.6 kg (vs 0.8 kg for placebo). In Part C, glucose variables improved in all groups, including placebo, suggesting a study effect in uncontrolled patients at baseline. Notwithstanding, AZP-531 60 µg/kg reduced HbA1c by 0.4% (vs 0.2% for placebo) and body weight by 2.1 kg (vs 1.3 kg for placebo). CONCLUSIONS: AZP-531 was well tolerated in this first-in-human study. Its pharmacokinetic profile, suitable for once-daily dosing, and metabolic effects support further clinical development for T2D.

The RHIC polarized H⁻ ion source.

A novel polarization technique had been successfully implemented for the Relativistic Heavy Ion Collider (RHIC) polarized H(-) ion source upgrade to higher intensity and polarization. In this technique, a proton beam inside the high magnetic field solenoid is produced by ionization of the atomic hydrogen beam (from external source) in the He-gaseous ionizer cell. Further proton polarization is produced in the process of polarized electron capture from the optically pumped Rb vapor. The use of high-brightness primary beam and large cross sections of charge-exchange cross sections resulted in production of high intensity H(-) ion beam of 85% polarization. The source very reliably delivered polarized beam in the RHIC Run-2013 and Run-2015. High beam current, brightness, and polarization resulted in 75% polarization at 23 GeV out of Alternating Gradient Synchrotron (AGS) and 60%-65% beam polarization at 100-250 GeV colliding beams in RHIC.

Effects of Fostamatinib on the Pharmacokinetics of Oral Contraceptive, Warfarin, and the Statins Rosuvastatin and Simvastatin: Results From Phase I Clinical Studies.

BACKGROUND AND OBJECTIVES: Fostamatinib is a spleen tyrosine kinase inhibitor that has been investigated as therapy for rheumatoid arthritis and immune thrombocytopenic purpura. The present studies assessed the potential for pharmacokinetic interaction between fostamatinib and the commonly prescribed medications oral contraceptive (OC), warfarin, and statins (rosuvastatin, simvastatin) in healthy subjects. METHODS: The OC study was a crossover study over two 28-day treatment periods (Microgynon(®) 30 plus placebo or fostamatinib). Concentrations of OC constituents (ethinyl estradiol/levonorgestrel) were measured. Effects on warfarin pharmacokinetics and pharmacodynamics were assessed (21-day study). Warfarin was administered on days 1 and 14, fostamatinib on days 8-20. The statin study was a two-period, fixed-sequence study of the effects of fostamatinib on exposure to rosuvastatin or simvastatin (single doses). Safety was assessed throughout. RESULTS: Fostamatinib co-administration with OC increased exposure to ethinyl estradiol [area under the plasma concentration-time curve at steady state (AUCss) 28% [confidence interval (CI 90%) 21-36]; maximum plasma concentration (Cmax) at steady state (Cmax,ss) 34% (CI 26-43)], but not levonorgestrel (AUCss 5%; Cmax,ss -3%), while exposure to luteinizing hormone and follicle-stimulating hormone decreased (≈ 20%). Fostamatinib did not affect the pharmacokinetics/pharmacodynamics of warfarin to a clinically relevant extent, but caused an upward trend in AUC for both R- and S-warfarin [18% (CI 13-23) and 13% (CI 7-19)]. Fostamatinib increased rosuvastatin AUC by 96% (CI 78-115) and Cmax by 88% (CI 69-110), and increased simvastatin acid AUC by 74% (CI 50-102) and Cmax by 83% (CI 57-113). CONCLUSION: Fostamatinib exhibits drug-drug interactions when co-administered with OC, simvastatin, or rosuvastatin, with the AUC of statins almost doubling. Fostamatinib did not exhibit a clinically relevant DDI on warfarin.

Pathology of congenital Zika syndrome in Brazil: a case series

Zika virus is an arthropod-borne virus that is a member of the family Flaviviridae transmitted mainly by mosquitoes of the genus Aedes. Although usually asymptomatic, infection can result in a mild and self-limiting illness characterised by fever, rash, arthralgia, and conjunctivitis. An increase in the number of children born with microcephaly was noted in 2015 in regions of Brazil with high transmission of Zika virus. More recently, evidence has been accumulating supporting a link between Zika virus and microcephaly. Here, we describe findings from three fatal cases and two spontaneous abortions associated with Zika virus infection.

Donor CD4 T Cell Diversity Determines Virus Reactivation in Patients After HLA-Matched Allogeneic Stem Cell Transplantation.

Delayed reconstitution of the T cell compartment in recipients of allogeneic stem cell grafts is associated with an increase of reactivation of latent viruses. Thereby, the transplanted T cell repertoire appears to be one of the factors that affect T cell reconstitution. Therefore, we studied the T cell receptor beta (TCRß) gene rearrangements of flow cytometry-sorted CD4(+) and CD8(+) T cells from the peripheral blood of 23 allogeneic donors before G-CSF administration and on the day of apheresis. For this purpose, TCRß rearrangements were amplified by multiplex PCR followed by high-throughput amplicon sequencing. Overall, CD4(+) T cells displayed a significantly higher TCRß diversity compared to CD8(+) T cells irrespective of G-CSF administration. In line, no significant impact of G-CSF treatment on the TCR Vß repertoire usage was found. However, correlation of the donor T cell repertoire with clinical outcomes of the recipient revealed that a higher CD4(+) TCRß diversity after G-CSF treatment is associated with lower reactivation of cytomegalovirus and Epstein-Barr virus. By contrast, no protecting correlation was observed for CD8(+) T cells. In essence, our deep TCRß analysis identifies the importance of the CD4(+) T cell compartment for the control of latent viruses after allogeneic stem cell transplantation.

Encephalitozoonosis in 2 South American Fur Seal (Arctocephalus australis) Pups.

Cerebral and disseminated encephalitozoonosis was diagnosed by histopathology, electron microscopy, and immunohistochemistry in 2 free-ranging South American fur seal pups found dead at Guafo Island (43°33'S 74°49'W) in southern Chile. In the brain, lesions were characterized by random foci of necrosis with large numbers of macrophages containing numerous microsporidial organisms within parasitophorous vacuoles. In addition, occasional histiocytes loaded with numerous mature and immature microsporidia spores consistent with Encephalitozoon sp were observed in pulmonary alveolar septa, splenic red pulp, glomerular capillaries, and proximal renal tubules by Gram and immunohistochemical stains. To our knowledge, microsporidial infection in a marine mammal species has not been previously reported.

Production, formation, and transport of high-brightness atomic hydrogen beam studies for the relativistic heavy ion collider polarized source upgrade.

The RHIC polarized H(-) ion source had been successfully upgraded to higher intensity and polarization by using a very high brightness fast atomic beam source developed at BINP, Novosibirsk. In this source the proton beam is extracted by a four-grid multi-aperture ion optical system and neutralized in the H2 gas cell downstream from the grids. The proton beam is extracted from plasma emitter with a low transverse ion temperature of ∼0.2 eV which is formed by plasma jet expansion from the arc plasma generator. The multi-hole grids are spherically shaped to produce "geometrical" beam focusing. Proton beam formation and transport of atomic beam were experimentally studied at test bench.

Hepatitis E in liver transplant recipients in the Rhône-Alpes region in France.

PURPOSE: In developed countries, hepatitis E virus (HEV) is considered an emerging pathogen, but prevalence seems highly variable according to previous European studies. As HEV can lead to chronic infections in immunosuppressed patients, it is thus essential to evaluate the prevalence and incidence of this infection. METHODS: We determined retrospectively, in a cohort of 206 pediatric and adult liver transplant recipients from the Rhône-Alpes region in France, pre-transplant anti-HEV-IgG prevalence and incidence of HEV infections during post-transplant follow-up (HEV IgG and IgM ± HEV-RNA). RESULTS: Transplantations were carried out between 2005 and 2012 and mean post-transplant follow-up was 32.8 months. Global pre-transplant prevalence of anti-HEV IgG was 29%, increasing regularly with age from 7% for children under 15 to 49% for patients older than 60. From the 142 seronegative patients before transplant, 11 seroconversions (7.7%) were observed during follow-up (incidence of 2.83 cases per 100 person-years). HEV RNA-tested at transaminases peak or randomly-was detected in only one case of seroconversion. For at least 2 HEV-seropositive patients, who had negative RNAemia before transplantation, viral RNA was detected chronically during follow-up, suggesting reinfection with HEV. CONCLUSION: Acute infections were largely more frequent than chronic infections and were asymptomatic or misdiagnosed, suggesting that liver transplant patients may not be particularly prone to developing severe HEV hepatitis. In addition, the presence of IgG anti-HEV may not protect against re-infection. Serological testing, therefore, appears to be of limited interest for the diagnosis of HEV infections in liver transplant recipients.

Infectious diseases specialty intervention is associated with decreased mortality and lower healthcare costs.

BACKGROUND: Previous studies, largely based on chart reviews with small sample sizes, have demonstrated that infectious diseases (ID) specialists positively impact patient outcomes. We investigated how ID specialists impact mortality, utilization, and costs using a large claims dataset. METHODS: We used administrative fee-for-service Medicare claims to identify beneficiaries hospitalized from 2008 to 2009 with at least 1 of 11 infections. There were 101 991 stays with and 170 336 stays without ID interventions. Cohorts were propensity score matched for patient demographics, comorbidities, and hospital characteristics. Regression models compared ID versus non-ID intervention and early versus late ID intervention. Risk-adjusted outcomes included hospital and intensive care unit (ICU) length of stay (LOS), mortality, readmissions, hospital charges, and Medicare payments. RESULTS: The ID intervention cohort demonstrated significantly lower mortality (odds ratio [OR], 0.87; 95% confidence interval [CI], .83 to .91) and readmissions (OR, 0.96; 95% CI, .93 to .99) than the non-ID intervention cohort. Medicare charges and payments were not significantly different; the ID intervention cohort ICU LOS was 3.7% shorter (95% CI, -5.5% to -1.9%). Patients receiving ID intervention within 2 days of admission had significantly lower 30-day mortality and readmission, hospital and ICU length of stay, and Medicare charges and payments compared with patients receiving later ID interventions. CONCLUSIONS: ID interventions are associated with improved patient outcomes. Early ID interventions are also associated with reduced costs for Medicare beneficiaries with select infections.

Changes in intracellular metabolite pools during growth of adherent MDCK cells in two different media.

In bioprocess engineering, the growth of continuous cell lines is mainly studied with respect to the changes in cell concentration, the resulting demand for substrates, and the accumulation of extracellular metabolites. The underlying metabolic process rests upon intracellular metabolite pools and their interaction with enzymes in the form of substrates, products, or allosteric effectors. Here, we quantitatively analyze time courses of 29 intracellular metabolites of adherent Madin-Darby canine kidney cells during cultivation in a serum-containing medium and a serum-free medium. The cells, which originated from the same pre-culture, showed similar overall growth behavior and only slight differences in their demand for the substrates glucose (GLC), glutamine (GLN), and glutamate (GLU). Analysis of intracellular metabolites, which mainly cover the glycolytic pathway, the citric acid cycle, and the nucleotide pools, revealed surprisingly similar dynamics for both cultivation conditions. Instead of a strong influence of the medium, we rather observed a growth phase-specific behavior in glycolysis and in the lower citric acid cycle. Furthermore, analysis of the lower part of glycolysis suggests the well-known regulation of pyruvate kinase by fructose 1,6-bisphosphate. The upper citric acid cycle (citrate, cis-aconitate, and isocitrate) is apparently uncoupled from the lower part (α-ketoglutarate, succinate, fumarate, and malate), which is in line with the characteristics of a truncated cycle. Decreased adenosine triphosphate and guanosine triphosphate pools, as well as a relatively low energy charge soon after inoculation of cells, indicate a high demand for cellular energy and the consumption of nucleotides for biosynthesis. We finally conclude that, with sufficient availability of substrates, the dynamics of GLC and GLN/GLU metabolism is influenced mainly by the cellular growth regime and regulatory function of key enzymes.