THE LECTOTYPE AND TYPE LOCALITY OF CANDOIA CARINATA (REPTILIA, SERPENTES)

The lectotype of Boa carinata Schneider, 1801, has been rediscovered and is now ZMFK35503, having been transferred in 1977 from the Göttingen Museum, its original location. Its typelocality has not been reported previously, but is indicated as “Amboina” on a label with the lectotype.The specimen is redescribed and fi gured, and conforms with expectations for material from the vicinityof the type locality. A brief history of Schneider and of the syntypes of Boa carinata, now Candoiacarinata, is reviewed

A closed-loop model of the respiratory system: Focus on hypercapnia and active expiration

Breathing is a vital process providing the exchange of gases between the lungs and atmosphere. During quiet breathing, pumping air from the lungs is mostly performed by contraction of the diaphragm during inspiration, and muscle contraction during expiration does not play a significant role in ventilation. In contrast, during intense exercise or severe hypercapnia forced or active expiration occurs in which the abdominal "expiratory" muscles become actively involved in breathing. The mechanisms of this transition remain unknown. To study these mechanisms, we developed a computational model of the closed-loop respiratory system that describes the brainstem respiratory network controlling the pulmonary subsystem representing lung biomechanics and gas (O2and CO2) exchange and transport. The lung subsystem provides two types of feedback to the neural subsystem: a mechanical one from pulmonary stretch receptors and a chemical one from central chemoreceptors. The neural component of the model simulates the respiratory network that includes several interacting respiratory neuron types within the Bötzinger and pre-Bötzinger complexes, as well as the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) representing the central chemoreception module targeted by chemical feedback. The RTN/pFRG compartment contains an independent neural generator that is activated at an increased CO2level and controls the abdominal motor output. The lung volume is controlled by two pumps, a major one driven by the diaphragm and an additional one activated by abdominal muscles and involved in active expiration. The model represents the first attempt to model the transition from quiet breathing to breathing with active expiration. The model suggests that the closed-loop respiratory control system switches to active expiration via a quantal acceleration of expiratory activity, when increases in breathing rate and phrenic amplitude no longer provide sufficient ventilation. The model can be used for simulation of closed-loop control of breathing under different conditions including respiratory disorders

Innate immune humoral factors, C1q and factor H, with differential pattern recognition properties, alter macrophage response to carbon nanotubes

Interaction between the complement system and carbon nanotubes (CNTs) can modify their intended biomedical applications. Pristine and derivatised CNTs can activate complement primarily via the classical pathway which enhances uptake of CNTs and suppresses pro-inflammatory response by immune cells. Here, we report that the interaction of C1q, the classical pathway recognition molecule, with CNTs involves charge pattern and classical pathway activation that is partly inhibited by factor H, a complement regulator. C1q and its globular modules, but not factor H, enhanced uptake of CNTs by macrophages and modulated the pro-inflammatory immune response. Thus, soluble complement factors can interact differentially with CNTs and alter the immune response even without complement activation. Coating CNTs with recombinant C1q globular heads offers a novel way of controlling classical pathway activation in nanotherapeutics. Surprisingly, the globular heads also enhance clearance by phagocytes and down-regulate inflammation, suggesting unexpected complexity in receptor interaction. From the Clinical Editor: Carbon nanotubes (CNTs) maybe useful in the clinical setting as targeting drug carriers. However, it is also well known that they can interact and activate the complement system, which may have a negative impact on the applicability of CNTs. In this study, the authors functionalized multi-walled CNT (MWNT), and investigated the interaction with the complement pathway. These studies are important so as to gain further understanding of the underlying mechanism in preparation for future use of CNTs in the clinical setting.L.P., A.G.T., L.K., G.S. and U.K. thank Brunel University London for strategic Infrastructure funding. H.A.K. acknowledges the Deanship of Scientific Research at King Saud University for funding via Group No. RGP-009

Systematic review of the safety and efficacy of foam sclerotherapy for venous disease of the lower limbs

Background: Foam sclerotherapy is a potential treatment for lower limb venous disease. Methods: A systematic review, with no restriction on study design, to assess the safety and efficacy of foam sclerotherapy. Results: 69 studies were included. For serious adverse events including pulmonary embolism and deep vein thrombosis, the median event rates were less than 1%. Median rate for visual disturbance was 1.4%. Median rates for some other adverse events were more common, including headache (4.2%), thrombophlebitis (4.7%), matting/skin staining/pigmentation (17.8%) and pain at the site of injection (25.6%). Median rate for complete occlusion of treated veins was 87.0% and for recurrence or development of new veins was 8.1%. Evidence from meta-analysis for complete occlusion suggests that foam sclerotherapy is associated with a lower rate compared with surgery (RR 0.86, 95% CI 0.67 to 1.10) and a higher rate compared with liquid sclerotherapy (RR 1.39, 95% CI 0.91 to 2.11). However, there was substantial heterogeneity across the studies in the meta-analysis. Conclusion: Serious adverse events were rare. There is insufficient evidence to reliably compare the effectiveness of foam sclerotherapy with other minimally invasive therapies or surgery. Evidence from high quality randomised controlled trials is required.This manuscript is based on a systematic review commissioned and funded by the National Institute for Health and Clinical Excellence (NICE) through its Interventional Procedures Programme. The Health Services Research Unit is supported by a core grant from the Chief Scientist Office of the Scottish Executive Health Department

Medication Complications in Extracorporeal Membrane Oxygenation.

The need for extracorporeal membrane oxygenation (ECMO) therapy is a marker of disease severity for which multiple medications are required. The therapy causes physiologic changes that impact drug pharmacokinetics. These changes can lead to exposure-driven decreases in efficacy or increased incidence of side effects. The pharmacokinetic changes are drug specific and largely undefined for most drugs. We review available drug dosing data and provide guidance for use in the ECMO patient population

A Multicenter Evaluation of Vancomycin-Associated Acute Kidney Injury in Hospitalized Patients with Acute Bacterial Skin and Skin Structure Infections

BACKGROUND: We sought to determine the real-world incidence of and risk factors for vancomycin-associated acute kidney injury (V-AKI) in hospitalized adults with acute bacterial skin and skin structure infections (ABSSSI). METHODS: Retrospective, observational, cohort study at ten U.S. medical centers between 2015 and 2019. Hospitalized patients treated with vancomycin (≥ 72 h) for ABSSSI and ≥ one baseline AKI risk factor were eligible. Patients with end-stage kidney disease, on renal replacement therapy or AKI at baseline, were excluded. The primary outcome was V-AKI by the vancomycin guidelines criteria. RESULTS: In total, 415 patients were included. V-AKI occurred in 39 (9.4%) patients. Independent risk factors for V-AKI were: chronic alcohol abuse (aOR 4.710, 95% CI 1.929-11.499), no medical insurance (aOR 3.451, 95% CI 1.310-9.090), ICU residence (aOR 4.398, 95% CI 1.676-11.541), Gram-negative coverage (aOR 2.926, 95% CI 1.158-7.392) and vancomycin duration (aOR 1.143, 95% CI 1.037-1.260). Based on infection severity and comorbidities, 34.7% of patients were candidates for oral antibiotics at baseline and 39.3% had non-purulent cellulitis which could have been more appropriately treated with a beta-lactam. Patients with V-AKI had significantly longer hospital lengths of stay (9 vs. 6 days, p = 0.001), higher 30-day readmission rates (30.8 vs. 9.0%, p \u3c 0.001) and increased all-cause 30-day mortality (5.1 vs. 0.3%, p = 0.024) CONCLUSIONS: V-AKI occurred in approximately one in ten ABSSSI patients and may be largely prevented by preferential use of oral antibiotics whenever possible, using beta-lactams for non-purulent cellulitis and limiting durations of vancomycin therapy