Shortcomings of cuffed paediatric tracheal tubes†

Background. The goal of this investigation was to evaluate adequacy of the design of readily available paediatric cuffed tracheal tubes (CPTT). Methods. In 15 series of cuffed (11) and uncuffed (four) paediatric tracheal tubes (ID: 2.5-7.0 mm) from four different manufacturers the following dimensions were measured: outer diameter of the tube, position and largest diameter of the tube cuff inflated at 20 cm H2O and position of depth markings and compared with age‐related dimensions. Results. Outer diameters for tubes with similar IDs varied markedly between manufacturers and between cuffed and uncuffed tracheal tubes from the same manufacturer. Cuff diameters at 20 cm H2O cuff pressure and cross‐sectional cuff area at 20 cm H2O cuff pressure did not always cover maximal internal age‐related tracheal diameters and cross‐sectional areas. Placing the tube tip in the mid‐trachea, the cuffs of cuffed tubes with ID 3.0, 4.0, or 5.0 mm would become positioned within the larynx. If the cuffs were placed 1 cm below the cricoid level, many of the tube tips would be dangerously deep within the trachea. Only five of the 11 cuffed tubes had a depth marking. In many of these tubes the distances from depth marking to tube tip were greater than the age‐related minimal tracheal length. Conclusion. Most cuffed paediatric tracheal tubes are poorly designed, in particular the smaller sizes. A better design of cuffed tubes with a short high‐volume, low‐pressure cuff, cuff‐free subglottic space and adequately placed depth markings are urgently needed. Br J Anaesth 2004; 92: 78-8

Pediatric epstein-barr virus carriers with or without tonsillar enlargement may substantially contribute to spreading of the virus

BACKGROUND: Human-to-human transmission of the persistent infection establishing Epstein-Barr virus (EBV) occurs via saliva. Tonsils act as important portal of entry and exit of EBV. The contagiousness of pediatric EBV carriers and the role played by tonsillar enlargement (TE) are not known. METHODS: We compared EBV shedding in mouthwash samples from pediatric EBV carriers with or without TE to that in mouthwash samples from pediatric patients with infectious mononucleosis (IM), the symptomatic form of primary infection if delayed after the age of 5 years. EBV DNA was quantified by polymerase chain reaction, and contagiousness was assessed using the cord lymphocyte transformation assay. RESULTS: EBV carriers with TE shed EBV DNA at an almost similar frequency (although in lower amounts) as pediatric patients with acute IM but more frequently (P <.001) and in higher amounts (P = .038) than EBV carriers without TE. EBV DNA levels in mouthwash samples from EBV carriers with TE mirrored levels in tonsils and gradually declined after tonsillectomy. Almost half of the mouthwash samples from pediatric EBV carriers contained infectious EBV. CONCLUSIONS: Pediatric EBV carriers--in particular, those with TE-may considerably contribute to the spreading of EBV in industrialized countries

Clinical evaluation of cuff and tube tip position in a newly designed paediatric preformed oral cuffed tracheal tube

Background. To assess the adequacy of the position of the tracheal tube cuff and tracheal tube tip in the recently introduced preformed oral Microcuff paediatric endotracheal tube (PET) using the manufacturers recommendations for Microcuff tracheal tube size selection. Methods. With Hospital Ethics Committee approval and informed parental consent, the tracheas of children from birth to adolescence were orally intubated with the preformed oral Microcuff PET. First, the position of the tracheal tube's intubation depth mark in relation to the vocal cords was assessed. Second, the distance ‘tracheal tube tip-to-carina' was endoscopically measured with the patient supine and the head in a neutral position and the tube placed with the centre mark at the lower incisors or alveolar ridge. Results. A total of 166 children aged from 0.1 to 16.4 yr (median 5.9 yr) were studied. In five patients the intubation depth mark was above (5 mm each), in 22 patients at the level of and in the remaining 139 patients below the vocal cords. No endobronchial intubation occurred. In four patients the distance ‘tracheal tube tip-to-carina' was smaller than the safety margin to prevent endobronchial intubation during head-neck flexion. Conclusion. The new oral preformed cuffed tracheal tubes allow safe placement in almost all patients when inserted according to the tube bend. The critically low tube tip and the high cuff positions in a few tubes when placed according to the tube bend requires clinical alertnes

An updated analysis of NN elastic scattering data to 1.6 GeV

An energy-dependent and set of single-energy partial-wave analyses of $NN$ elastic scattering data have been completed. The fit to 1.6~GeV has been supplemented with a low-energy analysis to 400 MeV. Using the low-energy fit, we study the sensitivity of our analysis to the choice of $\pi NN$ coupling constant. We also comment on the possibility of fitting $np$ data alone. These results are compared with those found in the recent Nijmegen analyses. (Figures may be obtained from the authors upon request.)Comment: 17 pages of text, VPI-CAPS-7/

Longitudinal Development of Reasons for Living and Dying With Suicide Attempters: A 2-Year Follow-Up Study

Background: Clinical interventions for patients after a suicide attempt might include a focus on Reasons for Living (RFL) and/or Reasons for Dying (RFD). The present study examined the longitudinal development of RFL and RFD in patients with and without a suicide-specific intervention - the Attempted Suicide Short Intervention Program (ASSIP). Methods: In this secondary analysis of a 2-year follow-up randomized controlled study, participants completed the Suicide Status Form II to assess RFL and RFD, at baseline, as well as at 6-, 12-, 18-, and 24-months follow-up. Growth models and latent class analysis were used to investigate longitudinal developments in RFL and RFD. Regression models were used to test the association between RFL, RFD and suicidal reattempts and ideation. Results: Cross-sectionally and longitudinally, RFD, but not RFL, were associated with suicide reattempts and suicidal ideation. The number of RFD decreased significantly across the 24 month period (from 1.90 at t1 to 1.04 at t5 in the control group and from 2.32 at t1 to 0.51 at t5 in the intervention group), and this decrease was stronger (b = −0.02; p = 0.004) in the ASSIP group than in the control group. There was no overall change in RFL. Three latent trajectories of RFD were identified: a decreasing (n = 77), a steady high (n = 17) and a trajectory with first increasing and then decreasing RFD (n = 26). The proportion of patients in the ASSIP intervention was highest in the decreasing trajectory and lowest in the steady high trajectory. Patients in the steady high trajectory were characterized by worse mental health and fewer social obligations (partner, children) at baseline. Conclusion: The results confirm the importance of RFD within the suicidal process and show that the number of RFD can be further reduced over the period of 24 months with short interventions such as ASSIP. The relevance of number of RFL in the suicidal process, as protective factor, was not confirmed. In the subgroup of patients whose RFD did not decrease over a long period of time, there is a particularly high risk of suicidal ideation/behavior. Clinical interventions should focus more closely on RFD, their etiology and maintenance

Oxidative stress-driven parvalbumin interneuron impairment as a common mechanism in models of schizophrenia.

Parvalbumin inhibitory interneurons (PVIs) are crucial for maintaining proper excitatory/inhibitory balance and high-frequency neuronal synchronization. Their activity supports critical developmental trajectories, sensory and cognitive processing, and social behavior. Despite heterogeneity in the etiology across schizophrenia and autism spectrum disorder, PVI circuits are altered in these psychiatric disorders. Identifying mechanism(s) underlying PVI deficits is essential to establish treatments targeting in particular cognition. On the basis of published and new data, we propose oxidative stress as a common pathological mechanism leading to PVI impairment in schizophrenia and some forms of autism. A series of animal models carrying genetic and/or environmental risks relevant to diverse etiological aspects of these disorders show PVI deficits to be all accompanied by oxidative stress in the anterior cingulate cortex. Specifically, oxidative stress is negatively correlated with the integrity of PVIs and the extracellular perineuronal net enwrapping these interneurons. Oxidative stress may result from dysregulation of systems typically affected in schizophrenia, including glutamatergic, dopaminergic, immune and antioxidant signaling. As convergent end point, redox dysregulation has successfully been targeted to protect PVIs with antioxidants/redox regulators across several animal models. This opens up new perspectives for the use of antioxidant treatments to be applied to at-risk individuals, in close temporal proximity to environmental impacts known to induce oxidative stress

Glutathione and glutamate in schizophrenia: a 7T MRS study

In schizophrenia, abnormal neural metabolite concentrations may arise from cortical damage following neuroinflammatory processes implicated in acute episodes. Inflammation is associated with increased glutamate, whereas the antioxidant glutathione may protect against inflammation-induced oxidative stress. We hypothesized that patients with stable schizophrenia would exhibit a reduction in glutathione, glutamate and/or glutamine in the cerebral cortex, consistent with a postinflammatory response, and that this reduction would be most marked in patients with residual schizophrenia an early stage with positive psychotic symptoms has progressed to a late stage characterised by long-term negative symptoms and impairments. We recruited 28 patients with stable schizophrenia and 45 healthy participants matched for age, gender and parental socio-economic status. We measured glutathione, glutamate and glutamine concentrations in the anterior cingulate cortex (ACC), left insula, and visual cortex using 7T proton Magnetic Resonance Spectroscopy (MRS). Glutathione and glutamate were significantly correlated in all three voxels. Glutamine concentrations across the three voxels were significantly correlated with each other. Principal Components Analysis (PCA) produced three clear components: an ACC glutathione-glutamate component; an insula-visual glutathione-glutamate component; and a glutamine component. Patients with stable schizophrenia had significantly lower scores on the ACC glutathione-glutamate component, an effect almost entirely leveraged by the sub-group of patients with residual schizophrenia. All three metabolite concentration values in the ACC were significantly reduced in this group. These findings are consistent with the hypothesis that excito-toxicity during the acute phase of illness leads to reduced glutathione and glutamate in the residual phase of the illness

Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis.

Molecular, genetic and pathological evidence suggests that deficits in GABAergic parvalbumin-positive interneurons contribute to schizophrenia pathophysiology through alterations in the brain's excitation-inhibition balance that result in impaired behaviour and cognition. Although the factors that trigger these deficits are diverse, there is increasing evidence that they converge on a common pathological hub that involves NMDA receptor hypofunction and oxidative stress. These factors have been separately linked to schizophrenia pathogenesis, but evidence now suggests that they are mechanistically interdependent and contribute to a common schizophrenia-associated pathology

Phenotypic and genotypic characterization of Neisseria gonorrhoeae isolates among individuals at high risk for sexually transmitted diseases in Zurich, Switzerland

Background: While ceftriaxone resistance remains scarce in Switzerland, global Neisseria gonorrhoeae (NG) antimicrobial resistance poses an urgent threat. This study describes clinical characteristics in MSM (men who have sex with men) diagnosed with NG infection and analyses NG resistance by phenotypic and genotypic means. Methods: Data of MSM enrolled in three clinical cohorts with a positive polymerase chain reaction test (PCR) for NG were analysed between January 2019 and December 2021 and linked with antibiotic susceptibility testing. Bacterial isolates were subjected to whole genome sequencing (WGS). Results: Of 142 participants, 141 (99%) were MSM and 118 (84%) living with HIV. Participants were treated with ceftriaxone ( N = 79), azithromycin ( N = 2), or a combination of both ( N = 61). No clinical or microbiological failures were observed. From 182 positive PCR samples taken, 23 were available for detailed analysis. Based on minimal inhibitory concentrations (MICs), all isolates were susceptible to ceftriaxone, gentamicin, cefixime, cefpodoxime, ertapenem, zoliflodacin, and spectinomycin. Resistance to azithromycin, tetracyclines and ciprofloxacin was observed in 10 (43%), 23 (100%) and 11 (48%) of the cases, respectively. Analysis of WGS data revealed combinations of resistance determinants that matched with the corresponding phenotypic resistance pattern of each isolate. Conclusion: Among the MSM diagnosed with NG mainly acquired in Switzerland, ceftriaxone MICs were low for a subset of bacterial isolates studied and no treatment failures were observed. For azithromycin, high occurrences of in vitro resistance were found. Gentamicin, cefixime, cefpodoxime, ertapenem, spectinomycin, and zoliflodacin displayed excellent in vitro activity against the 23 isolates underscoring their potential as alternative agents to ceftriaxone