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Abstract Background Cognitive impairment is a common medical issue in rat sarcoma (RAS) pathway disorders, so-called RASopathies, like Neurofibromatosis type 1 (NF1) or Noonan syndrome (NS). It is presumed to be caused by impaired synaptic plasticity. In animal studies, pathway-specific pharmacological interventions with lovastatin (LOV) and lamotrigine (LTG) have been shown to improve synaptic plasticity as well as cognitive function. The aim of this clinical trial is to translate the findings of animal studies to humans and to probe the effect of lovastatin (NS) and lamotrigine (NS and NF1) on synaptic plasticity and cognitive function/alertness in RASopathies. Methods Within this phase IIa, monocentre, randomized, double-blind, parallel-group, placebo-controlled, cross-over clinical trial (syn. SynCoRAS), three approaches (approaches I–III) will be carried out. In patients with NS, the effect of LTG (approach I) and of LOV (approach II) is investigated on synaptic plasticity and alertness. LTG is tested in patients with NF1 (approach III). Trial participants receive a single dose of 300 mg LTG or placebo (I and III) and 200 mg LOV or placebo (II) daily for 4 days with a cross-over after at least 7 days. Synaptic plasticity is investigated using a repetitive high-frequency transcranial magnetic stimulation (TMS) protocol called quadri-pulse theta burst stimulation (qTBS). Attention is examined by using the test of attentional performance (TAP). Twenty-eight patients are randomized in groups NS and NF1 with n = 24 intended to reach the primary endpoint (change in synaptic plasticity). Secondary endpoints are attention (TAP) and differences in short interval cortical inhibition (SICI) between placebo and trial medication (LTG and LOV). Discussion The study is targeting impairments in synaptic plasticity and cognitive impairment, one of the main health problems of patients with RASopathies. Recent first results with LOV in patients with NF1 have shown an improvement in synaptic plasticity and cognition. Within this clinical trial, it is investigated if these findings can be transferred to patients with NS. LTG is most likely a more effective and promising substance improving synaptic plasticity and, consecutively, cognitive function. It is expected that both substances are improving synaptic plasticity as well as alertness. Changes in alertness may be a precondition for improvement of cognition. Trial registration The clinical trial is registered in ClinicalTrials.gov (NCT03504501; https://www.clinicaltrials.gov ; date of registration: 04/11/2018) and in EudraCT (number 2016–005022-10).

Different blood group systems have been characterized in people and other mammals. In domestic cats, the ABC blood group system plays the most important clinical role and has been investigated extensively—from the phenotype to the molecular genetics. In non-domestic felids, phenotypic ABC blood typing has been performed by different methods to detect the antigens, but the four informative CMAH markers in domestic cats were not able to identify types B and C (AB) in non-domestic cats. In this study, 138 blood samples from 15 non-domestic (wild) felid species were investigated by CMAH exonic sequencing and genotyping for putative variants causing type B or C (AB) and correlation to the respective ABC blood phenotype. A total of 58 CMAH variants were found, including 15 missense and 43 synonymous CMAH variants. One variant (c.635G>C) was concordant with blood type B (and C) in cheetahs and type B in cougars, compared to blood type A in all other felid species (lion, tiger, Canada lynx, snow leopard, clouded leopard, serval, jaguar, fishing cat, Pallas cat, bobcat, black footed cat, leopard, and sand cat). Since cheetahs and cougars belong to the genera puma, it could not be determined if the common CMAH variant is either a marker for type B (or C) or is just common in pumas.

[This corrects the article DOI: 10.1371/journal.pone.0281978.].

Abstract Background Without aggressive treatment, pulmonary arterial hypertension (PAH) has a 5-year mortality of approximately 40%. A patient’s response to vasodilators at diagnosis impacts the therapeutic options and prognosis. We hypothesized that analyzing perfusion images acquired before and during vasodilation could identify characteristic differences between PAH and control subjects. Methods We studied 5 controls and 4 subjects with PAH using HRCT and 13NN PET imaging of pulmonary perfusion and ventilation. The total spatial heterogeneity of perfusion (CV2 Qtotal) and its components in the vertical (CV2 Qvgrad) and cranio-caudal (CV2 Qzgrad) directions, and the residual heterogeneity (CV2 Qr), were assessed at baseline and while breathing oxygen and nitric oxide (O2 + iNO). The length scale spectrum of CV2 Qr was determined from 10 to 110 mm, and the response of regional perfusion to O2 + iNO was calculated as the mean of absolute differences. Vertical gradients in perfusion (Qvgrad) were derived from perfusion images, and ventilation-perfusion distributions from images of 13NN washout kinetics. Results O2 + iNO significantly enhanced perfusion distribution differences between PAH and controls, allowing differentiation of PAH subjects from controls. During O2 + iNO, CV2 Qvgrad was significantly higher in controls than in PAH (0.08 (0.055–0.10) vs. 6.7 × 10–3 (2 × 10–4–0.02), p

Abstract Background Postoperative surgical site infections (SSIs) remain common after laparotomy for resections of the gastrointestinal or hepatobiliary tract. Especially organ/space infections (CDC class III SSI) can be life-threatening, require relaparotomy, intensive care or interventional drainage of intraabdominal abscesses. The PAISI study aims to investigate whether the use of prophylactic peritoneal irrigation with NaOCl/HOCl solution can reduce the SSI rates following laparotomy for resections of the gastrointestinal or hepatobiliary tract, compared to standard irrigation with physiological electrolyte solution (Ringer’s solution). Secondarily, to evaluate whether the use of prophylactic peritoneal irrigation with NaOCl/HOCl solution can reduce postoperative morbidity and mortality as well as the rate of re-operations and length of hospital stay. Methods PAISI is a prospective, randomized, observer- and patient-blinded, monocentric, two-arm surgical study in an adaptive parallel groups design, comparing peritoneal and wound irrigation with NaOCl/HOCl (50/50ppm) solution to irrigation with Ringer’s solution. The primary endpoint of the study is the SSI rate within 30 days postoperatively. Since there is no data on incidence rates from randomized clinical trials, the rates for sample size calculation were estimated according to the clinical experience at our institution. Therefore, the study design includes one unblinded look at the data by a second statistician, which will be performed after half of the patients reached the primary endpoint. This interim information will be used to check the assumptions and if needed, the sample size will be adjusted. The O’Brien-Fleming spending function is used to determine the efficacy test boundary and the non-binding futility boundary. The one-sided z-test (Group sequential test of two proportions) at the 2.5% significance level with a total of two looks at the data will have overall 80% power. Discussion The results of this study will provide high-level evidence for future research and clinical recommendations regarding the use of NaOCl/HOCl solution in abdominal surgery and provide the participating patients the opportunity of a potentially improved treatment. Trial registration German Clinical Trials Register (DRKS) DRKS00028037. Registered on 27 May 2022.