The social, psychological, and physical impact of COVID-19 restrictions for institutionalized adults with intellectual and developmental disabilities.

During the COVID-19 pandemic, drastic measures to interrupt SARS-CoV-2 infection chains were implemented. In our study we investigated the consequences of pandemic related restrictions on the social, psychological, and physical well-being of institutionalized adults with intellectual and developmental disabilities. Methods: Online survey among professional caregivers in 71 residential groups, caring for 848 residents. Findings: (i.) A lack of participation concerning infection protection measures of the residents, their relatives, and their caregivers; (ii.) A 20% increase in doctor contacts during the pandemic; (iii.) A considerable deterioration in at least one item of the subdomains mood (49%), everyday skills (51%), social interaction (29%), exercise and coordination skills (12%), behavior (11%) and cognition and communication (7%); (iv.) A deterioration of the overall condition in 41%; Summery: Intensive attempts should be made to find individual and less categorical contra-infectious measures without questioning the basic everyday needs of people with intellectual and developmental disabilities.

Internal genes of a highly pathogenic H5N1 influenza virus determine high viral replication in myeloid cells and severe outcome of infection in mice.

The highly pathogenic avian influenza (HPAI) H5N1 influenza virus has been a public health concern for more than a decade because of its frequent zoonoses and the high case fatality rate associated with human infections. Severe disease following H5N1 influenza infection is often associated with dysregulated host innate immune response also known as cytokine storm but the virological and cellular basis of these responses has not been clearly described. We rescued a series of 6:2 reassortant viruses that combined a PR8 HA/NA pairing with the internal gene segments from human adapted H1N1, H3N2, or avian H5N1 viruses and found that mice infected with the virus with H5N1 internal genes suffered severe weight loss associated with increased lung cytokines but not high viral load. This phenotype did not map to the NS gene segment, and NS1 protein of H5N1 virus functioned as a type I IFN antagonist as efficient as NS1 of H1N1 or H3N2 viruses. Instead we discovered that the internal genes of H5N1 virus supported a much higher level of replication of viral RNAs in myeloid cells in vitro, but not in epithelial cells and that this was associated with high induction of type I IFN in myeloid cells. We also found that in vivo during H5N1 recombinant virus infection cells of haematopoetic origin were infected and produced type I IFN and proinflammatory cytokines. Taken together our data infer that human and avian influenza viruses are differently controlled by host factors in alternative cell types; internal gene segments of avian H5N1 virus uniquely drove high viral replication in myeloid cells, which triggered an excessive cytokine production, resulting in severe immunopathology.

[Analysis of a first responder system for emergency medical care in rural areas: first results and experiences]. / Analyse eines First-responder-Systems zur notfallmedizinischen Versorgung im ländlichen Raum: erste Ergebnisse und Erfahrungen.

BACKGROUND: In emergency situations it is essential to get access to medical treatment as early as possible. In Germany, the time interval from alarm to arrival should be less than 10-15 min. The emergency medical service (EMS) cannot comply with this recommendation in approximately 10% of the emergencies in Baden-Württemberg. In addition to the traditional EMS system, a voluntary system of first responders has been developed over the last years to reduce this interval. They are incorporated into the alarm system of the traditional EMS and are alarmed as soon as an emergency call arrives. Data on process times (from alarm to begin of treatment or duration of treatment until arrival of EMS) and quality are rare. In Baden-Württemberg, the emergency aid "Deutsche Lebens-Rettungs-Gesellschaft e.V. (DLRG)" Nordhardt can only estimate times and quality of primary care. The objective of this analysis was to describe and evaluate such a first responder system. METHODS: The presented study investigated the emergency responses of a first responder system in Nordhardt, close to Karlsruhe, Germany. A total of 367 emergency data sets from 2017 containing information on operating time, medical history, suspected diagnosis and medical treatment, were evaluated. Of these, 363 anonymized emergency records including the complete information (concerning process time and medical treatment) were analyzed. The focus was on different time intervals from alarm to treatment and until arrival of the EMS. Additionally, the quality of medical treatment and the measured vital data were examined. RESULTS: The median response time and time to access to the patient was 2 min in both. The patient was reached within approximately 4 min and treated for another 5 min until the EMS arrived. In two thirds of the patients, the vital parameters were measured, 5 patients were resuscitated, 23 received supplementary oxygen, 4 patients were ventilated and 11 patients suffering from hypoglycemia showed a clinical benefit from the early treatment. A total of 50 trauma patients were treated, 5 with cervical spine stabilization and 38 received a body check. CONCLUSION: The first responders from Nordhardt received an emergency call nearly every day. In two thirds of the calls they were faster than the EMS as they usually have local sites with a shorter distance to the emergency scene where they are able to deal with critical medical cases until the EMS arrives. Despite the small case numbers, it could be concluded that the early medical treatment with respect to resuscitation based on earlier arrival on site may help to increase the survival rate of patients. The first responders were also able to manage airway problems with additional oxygen or other airway devices. Other medical treatment performed by the first responders, such as administration of glucose in hypoglycemic patients positively affected the patient's condition. There is a tactical advantage to include first responders in traditional EMS services. Further studies are needed to examine these questions in larger samples also over a longer time period. Standardization and digitalization of the records could help to gain more data in this field.

Low left amygdala volume is associated with a longer duration of unipolar depression.

The amygdala plays a crucial role in the pathogenesis of major depressive disorder (MDD). While robust findings support a negative impact of illness duration on hippocampal volume in MDD, morphometric studies of the amygdala have yielded inhomogeneous results. Considering the methodical problems of automatic segmentation methods, a standardized segmentation protocol with proven inter- and intra-rater reliability was employed using high-resolution magnetic resonance imaging. To identify the effect of MDD on amygdala morphometry, 23 unipolar depressed patients who responded to antidepressant medication and 30 age-matched healthy controls (HC) were enrolled. First, gray matter volumes (GMV) of the bilateral amygdala were delineated manually in 3D by three blinded experts using the MultiTracer. The whole brain GMV was determined by using voxel-based morphometry. Second, the differences of the whole brain and the bilateral amygdala GMV values between MDD and HC were calculated with t-statistics. The GMV of the whole brain and the amygdala did not differ between HC and MDD patients. Third, MDD characteristics were correlated with amygdala GMV. Within the normal range, the left amygdala GMV was larger in patients with later onset and smaller in cases of prolonged depression. In line with prior reports of depressed patients responding to antidepressant treatment, amygdala GMV was negatively related to illness duration, suggesting volume loss with disease progression. It remains unclear as to whether the association between illness duration and GMV reduced left amygdala volume indicates a neurotoxic effect of prolonged MDD or is rather a negative predictor of chronic depression.

[Accidental central venous administation of 0.1 % chlorhexidine mouthwash]. / Akzidentelle zentralvenöse Verabreichung von 0,1 %iger Chlorhexidinmundspüllösung.

Medication errors are frequent and a serious safety concern. Chlorhexidine (CHX) is used daily in healthcare as a disinfectant. Its accidental intravascular injection is scarcely described. Serious complications, such as acute respiratory distress syndrome (ARDS) could be a consequence. We describe a case of central venous administration of 0.1% CHX mouthwash, its potential complications and possibilities of treatment. In contrast to another case report our patient had no detectable adverse side effects. The immediate hemofiltration and cleansing of the i. v. line may have contributed to this favorable outcome.

Allelic variation in CRHR1 predisposes to panic disorder: evidence for biased fear processing.

Corticotropin-releasing hormone (CRH) is a major regulator of the hypothalamic-pituitary-adrenal axis. Binding to its receptor CRHR1 triggers the downstream release of the stress response-regulating hormone cortisol. Biochemical, behavioral and genetic studies revealed CRHR1 as a possible candidate gene for mood and anxiety disorders. Here we aimed to evaluate CRHR1 as a risk factor for panic disorder (PD). Allelic variation of CRHR1 was captured by 9 single-nucleotide polymorphisms (SNPs), which were genotyped in 531 matched case/control pairs. Four SNPs were found to be associated with PD, in at least one sub-sample. The minor allele of rs17689918 was found to significantly increase risk for PD in females after Bonferroni correction and furthermore decreased CRHR1 mRNA expression in human forebrains and amygdalae. When investigating neural correlates underlying this association in patients with PD using functional magnetic resonance imaging, risk allele carriers of rs17689918 showed aberrant differential conditioning predominantly in the bilateral prefrontal cortex and safety signal processing in the amygdalae, arguing for predominant generalization of fear and hence anxious apprehension. Additionally, the risk allele of rs17689918 led to less flight behavior during fear-provoking situations but rather increased anxious apprehension and went along with increased anxiety sensitivity. Thus reduced gene expression driven by CRHR1 risk allele leads to a phenotype characterized by fear sensitization and hence sustained fear. These results strengthen the role of CRHR1 in PD and clarify the mechanisms by which genetic variation in CRHR1 is linked to this disorder.

Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group.

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

Shotgun glycomics of pig lung identifies natural endogenous receptors for influenza viruses.

Influenza viruses bind to host cell surface glycans containing terminal sialic acids, but as studies on influenza binding become more sophisticated, it is becoming evident that although sialic acid may be necessary, it is not sufficient for productive binding. To better define endogenous glycans that serve as viral receptors, we have explored glycan recognition in the pig lung, because influenza is broadly disseminated in swine, and swine have been postulated as an intermediary host for the emergence of pandemic strains. For these studies, we used the technology of "shotgun glycomics" to identify natural receptor glycans. The total released N- and O-glycans from pig lung glycoproteins and glycolipid-derived glycans were fluorescently tagged and separated by multidimensional HPLC, and individual glycans were covalently printed to generate pig lung shotgun glycan microarrays. All viruses tested interacted with one or more sialylated N-glycans but not O-glycans or glycolipid-derived glycans, and each virus demonstrated novel and unexpected differences in endogenous N-glycan recognition. The results illustrate the repertoire of specific, endogenous N-glycans of pig lung glycoproteins for virus recognition and offer a new direction for studying endogenous glycan functions in viral pathogenesis.

[Ventilator-associated pneumonia (VAP) : A risk already at the time of anesthetic induction]. / Ventilatorassoziierte Pneumonie (VAP) : Bereits ein Thema bei der Narkoseeinleitung.

BACKGROUND: Ventilator-associated pneumonia (VAP) is one of the most common and preventable infections in mechanically ventilated patients. It is associated with a high mortality rate. To prevent VAP, various strategies address this issue using "VAP-bundles", which are implemented in many intensive care units. The risk of acquiring VAP starts with the induction of anesthesia, strictly speaking at the time of intubation. This article considers measures to prevent VAP during general anesthesia in adult patients (>18 years). Procedures beyond standard hygienic precautions for VAP prevention are reviewed. METHODS: A literature search in different databases (PubMed, Cochrane, Ovid und CINAHL) over the last five years. RESULTS: Beyond standard hygienic precautions, microaspiration should be avoided to prevent VAP. During mechanical ventilation at least 5 cm H2O PEEP is advised. Continuous monitoring and adjustment of cuff pressure is necessary. All patients mechanically ventilated after general anesthesia for more than 24 h should be intubated with an ETT with a port for subglottic suctioning.

Multimodal imaging of a tescalcin (TESC)-regulating polymorphism (rs7294919)-specific effects on hippocampal gray matter structure.

In two large genome-wide association studies, an intergenic single-nucleotide polymorphism (SNP; rs7294919) involved in TESC gene regulation has been associated with hippocampus volume. Further characterization of neurobiological effects of the TESC gene is warranted using multimodal brain-wide structural and functional imaging. Voxel-based morphometry (VBM8) was used in two large, well-characterized samples of healthy individuals of West-European ancestry (Münster sample, N=503; SHIP-TREND, N=721) to analyze associations between rs7294919 and local gray matter volume. In subsamples, white matter fiber structure was investigated using diffusion tensor imaging (DTI) and limbic responsiveness was measured by means of functional magnetic resonance imaging (fMRI) during facial emotion processing (N=220 and N=264, respectively). Furthermore, gene x environment (G × E) interaction and gene x gene interaction with SNPs from genes previously found to be associated with hippocampal size (FKBP5, Reelin, IL-6, TNF-α, BDNF and 5-HTTLPR/rs25531) were explored. We demonstrated highly significant effects of rs7294919 on hippocampal gray matter volumes in both samples. In whole-brain analyses, no other brain areas except the hippocampal formation and adjacent temporal structures were associated with rs7294919. There were no genotype effects on DTI and fMRI results, including functional connectivity measures. No G × E interaction with childhood maltreatment was found in both samples. However, an interaction between rs7294919 and rs2299403 in the Reelin gene was found that withstood correction for multiple comparisons. We conclude that rs7294919 exerts highly robust and regionally specific effects on hippocampal gray matter structures, but not on other neuropsychiatrically relevant imaging markers. The biological interaction between TESC and RELN pointing to a neurodevelopmental origin of the observed findings warrants further mechanistic investigations.

MAOA and mechanisms of panic disorder revisited: from bench to molecular psychotherapy.

Panic disorder with agoraphobia (PD/AG) is a prevalent mental disorder featuring a substantial complex genetic component. At present, only a few established risk genes exist. Among these, the gene encoding monoamine oxidase A (MAOA) is noteworthy given that genetic variation has been demonstrated to influence gene expression and monoamine levels. Long alleles of the MAOA-uVNTR promoter polymorphism are associated with PD/AG and correspond with increased enzyme activity. Here, we have thus investigated the impact of MAOA-uVNTR on therapy response, behavioral avoidance and brain activity in fear conditioning in a large controlled and randomized multicenter study on cognitive behavioral therapy (CBT) in PD/AG. The study consisted of 369 PD/AG patients, and genetic information was available for 283 patients. Carriers of the risk allele had significantly worse outcome as measured by the Hamilton Anxiety scale (46% responders vs 67%, P=0.017). This was accompanied by elevated heart rate and increased fear during an anxiety-provoking situation, that is, the behavioral avoidance task. All but one panic attack that happened during this task occurred in risk allele carriers and, furthermore, risk allele carriers did not habituate to the situation during repetitive exposure. Finally, functional neuroimaging during a classical fear conditioning paradigm evidenced that the protective allele is associated with increased activation of the anterior cingulate cortex upon presentation of the CS+ during acquisition of fear. Further differentiation between high- and low-risk subjects after treatment was observed in the inferior parietal lobes, suggesting differential brain activation patterns upon CBT. Taken together, we established that a genetic risk factor for PD/AG is associated with worse response to CBT and identify potential underlying neural mechanisms. These findings might govern how psychotherapy can include genetic information to tailor individualized treatment approaches.

[Sudden cardiac death during a city marathon run]. / Plötzlicher Herztod beim Stadtmarathon.

Sudden cardiac death (SCD) in young athletes during physical stress is a rare event with an incidence of 1-3 deaths per 100,000 athletes per year. A coronary anomaly is the second most common cause of death following hypertrophic cardiomyopathy. Symptomatic prodromes occur in 20% of cases prior to the SCD event. This case report describes a 35-year-old male who collapsed near the finishing line of a half marathon run. Despite immediate resuscitation attempts and initial return of spontaneous circulation (ROSC), a pulseless electrical activity (PEA) followed and the patient died 1 h after arrival in the resuscitation unit. The autopsy revealed an anomalous left coronary artery (ALCA), which can lead to ischemia of the respective heart muscles under severe stress.

[Cognitive deficits in unipolar major depression]. / Kognitive Störungen bei unipolarer Depression.

Cognitive deficits are common symptom presentations in neurology and psychiatry. Cognitive symptoms during major depressive episodes cause subjective distress as well as difficulties during therapy and psychosocial reintegration. Depression-associated cognitive symptoms are characterized by a mood-congruent information processing bias as well as by cognitive performance deficits. A diagnostically relevant profile of neuropsychological impairments specific to depression has not yet been identified. Nevertheless, deficits of executive and declarative memory functions have repeatedly been reported. The time course of cognitive deficits after remission of mood is not entirely clear. Depending on the point of time of the reinvestigation, patients may still exhibit pronounced cognitive deficits. This article presents the current knowledge about cognitive symptoms in major depression, including the pathophysiology and treatment options.

Altered top-down and bottom-up processing of fear conditioning in panic disorder with agoraphobia.

BACKGROUND: Although several neurophysiological models have been proposed for panic disorder with agoraphobia (PD/AG), there is limited evidence from functional magnetic resonance imaging (fMRI) studies on key neural networks in PD/AG. Fear conditioning has been proposed to represent a central pathway for the development and maintenance of this disorder; however, its neural substrates remain elusive. The present study aimed to investigate the neural correlates of fear conditioning in PD/AG patients. METHOD: The blood oxygen level-dependent (BOLD) response was measured using fMRI during a fear conditioning task. Indicators of differential conditioning, simple conditioning and safety signal processing were investigated in 60 PD/AG patients and 60 matched healthy controls. RESULTS: Differential conditioning was associated with enhanced activation of the bilateral dorsal inferior frontal gyrus (IFG) whereas simple conditioning and safety signal processing were related to increased midbrain activation in PD/AG patients versus controls. Anxiety sensitivity was associated positively with the magnitude of midbrain activation. CONCLUSIONS: The results suggest changes in top-down and bottom-up processes during fear conditioning in PD/AG that can be interpreted within a neural framework of defensive reactions mediating threat through distal (forebrain) versus proximal (midbrain) brain structures. Evidence is accumulating that this network plays a key role in the aetiopathogenesis of panic disorder.

Functional glycomic analysis of human milk glycans reveals the presence of virus receptors and embryonic stem cell biomarkers.

Human milk contains a large diversity of free glycans beyond lactose, but their functions are not well understood. To explore their functional recognition, here we describe a shotgun glycan microarray prepared from isolated human milk glycans (HMGs), and our studies on their recognition by viruses, antibodies, and glycan-binding proteins (GBPs), including lectins. The total neutral and sialylated HMGs were derivatized with a bifunctional fluorescent tag, separated by multidimensional HPLC, and archived in a tagged glycan library, which was then used to print a shotgun glycan microarray (SGM). This SGM was first interrogated with well defined GBPs and antibodies. These data demonstrated both the utility of the array and provided preliminary structural information (metadata) about this complex glycome. Anti-TRA-1 antibodies that recognize human pluripotent stem cells specifically recognized several HMGs that were then further structurally defined as novel epitopes for these antibodies. Human influenza viruses and Parvovirus Minute Viruses of Mice also specifically recognized several HMGs. For glycan sequencing, we used a novel approach termed metadata-assisted glycan sequencing (MAGS), in which we combine information from analyses of glycans by mass spectrometry with glycan interactions with defined GBPs and antibodies before and after exoglycosidase treatments on the microarray. Together, these results provide novel insights into diverse recognition functions of HMGs and show the utility of the SGM approach and MAGS as resources for defining novel glycan recognition by GBPs, antibodies, and pathogens.

Mutation tryptophan to leucine at position 222 of haemagglutinin could facilitate H3N2 influenza A virus infection in dogs.

An avian-like H3N2 influenza A virus (IAV) has recently caused sporadic canine influenza outbreaks in China and Korea, but the molecular mechanisms involved in the interspecies transmission of H3N2 IAV from avian to canine species are not well understood. Sequence analysis showed that residue 222 in haemagglutinin (HA) is predominantly tryptophan (W) in the closely related avian H3N2 IAV, but was leucine (L) in canine H3N2 IAV. In this study, reassortant viruses rH3N2-222L (canine-like) and rH3N2-222W (avian-like) with HA mutation L222W were generated using reverse genetics to evaluate the significance of the L222W mutation on receptor binding and host tropism of H3N2 IAV. Compared with rH3N2-222W, rH3N2-222L grew more rapidly in MDCK cells and had significantly higher infectivity in primary canine tracheal epithelial cells. Tissue-binding assays demonstrated that rH3N2-222L had a preference for canine tracheal tissues rather avian tracheal tissues, whereas rH3N2-222W favoured slightly avian rather canine tracheal tissues. Glycan microarray analysis suggested both rH3N2-222L and rH3N2-222W bound preferentially to α2,3-linked sialic acids. However, the rH3N2-222W had more than twofold less binding affinity than rH3N2-222L to a set of glycans with Neu5Aca2-3Galb1-4(Fuca-)-like or Neu5Aca2-3Galb1-3(Fuca-)-like structures. These data suggest the W to L mutation at position 222 of the HA could facilitate infection of H3N2 IAV in dogs, possibly by increasing the binding affinities of the HA to specific receptors with Neu5Aca2-3Galb1-4(Fuca-) or Neu5Aca2-3Galb1-3(Fuca-)-like structures that are present in dogs.

Structural changes of central white matter tracts in Kennedy's disease - a diffusion tensor imaging and voxel-based morphometry study.

OBJECTIVES: Spinobulbar muscular atrophy [Kennedy's disease (KD)] is a rare X-linked neurodegenerative disorder of mainly spinal and bulbar motoneurons. Recent studies suggest a multisystem character of this disease. The aim of this study was to identify and characterize structural changes of gray (GM) and white matter (WM) in the central nervous system. MATERIAL AND METHODS: Whole-brain-based voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) analyses were applied to MRI data of eight genetically proven patients with KD and compared with 16 healthy age-matched controls. RESULTS: Diffusion tensor imaging analysis showed not only decreased fractional anisotropy (FA) values in the brainstem, but also widespread changes in central WM tracts, whereas VBM analysis of the WM showed alterations primarily in the brainstem and cerebellum. There were no changes in GM volume. The FA value decrease in the brainstem correlated with the disease duration. CONCLUSION: Diffusion tensor imaging analysis revealed subtle changes of central WM tract integrity, while GM and WM volume remained unaffected. In our patient sample, KD had more extended effects than previously reported. These changes could either be attributed primarily to neurodegeneration or reflect secondary plastic changes due to atrophy of lower motor neurons and reorganization of cortical structures.

[Pediatric postoperative quality analysis : Pain and postoperative nausea and vomiting]. / Postoperative Qualitätsanalyse bei Kindern : Schmerz sowie postoperative Übelkeit und Erbrechen.

BACKGROUND: For the evaluation of postoperative pain therapy, nausea and vomiting (PONV), the Children's Hospital in Lucerne acts as a member of the postoperative quality improvement project QUIPSi for children. Initial results and the potential for evaluation of the postoperative pain therapy and PONV are presented here. The central questions are whether the postoperative therapy concept is sufficient and if QUIPSi serves as an ideal tool for postoperative quality improvement? METHODS: Over a period of 1.5 years a total of 460 children aged between 4 to 17 years evaluated their postoperative pain, requirements for more analgesic medicine and the incidence of PONV according to a standardized questionnaire on the first postoperative day. The administration of analgesic medicine was recorded until finishing the questionnaire. RESULTS: In this study 5 pediatric outpatient operation groups (hernia repair n = 36, bone surgery n = 23, metal removal surgery n = 31, circumcision n = 65 and soft tissue surgery n = 49) and 9 pediatric inpatient operation groups (appendectomy n = 21, bone surgery n = 78, metal removal surgery n = 24, orchidopexy n = 31, combined operation (orchidopexy + hernia repair or circumcision) n = 14, otoplasty n = 9, tonsillectomy n = 41 and pectus excavatum surgery n = 6 and soft tissue surgery n=28) could be classified. All operation groups except the inpatient and outpatient soft tissue surgery groups received regional or infiltration anesthesia. Analgesic medicine was prescribed with the maximum permitted daily dose per kg body weight (paracetamol 100 mg/kgBW, metamizole 80 mg/kgBW, diclofenac 3 mg/kgBW and ibuprofen 40 mg/kgBW; in reserve tramadol 8 mg/kgBW and nalbuphine 2.4 mg/kgBW). The following operation groups complained of persistent pain (scale according to Hicks 0-10) and/or required more pain medicine (%): pediatric outpatients circumcision 5.1/19 %, pediatric inpatients appendectomy 6.5/43 %, tonsillectomy 6.4/32 %, pectus excavatum surgery 7.7/33 %, orchidopexy 4.2/19.4 %, otoplasty 3.1/22.2 %. The reason for the elevated postoperative pain was mainly insufficient administered pain medicine despite the prescription of the maximum daily dose per kg body weight or maybe due to a late administration. Circumcision/appendectomy/tonsillectomy/pectus excavatum surgery/orchidopexy/otoplasty (% of max. daily dose): paracetamol 5/58/99/36/57/37 %, metamizole 0,4/18/8/54/4/4 %, diclofenac 44/45/3/97/51/68 % or ibuprofen 42/1/0/0/0/0 %, tramadol 0,4/0/0/0/0/0 %, nalbuphine 0,4/1/16/0/2/0 %). As the standard inhalative general anesthesia and PONV prophylaxis with tropisetron (body weight: < 20 kg 1 mg, > 20 kg: 2 mg intravenous bolus) was performed. Dexamethasone (0.15-0.5 mg/kgBW, maximum allowed dose 8 mg intravenous bolus) was administered as a back-up drug for PONV. The nausea incidence was higher in the inpatient group (14-50 %) than in the outpatient group (10-29 %). The incidence of vomiting was higher in the inpatient (0-37 %) than in the outpatient group (3-17 %). CONCLUSIONS: The quality analysis showed that especially children with the requirement for more pain medicine and a high PONV incidence (inpatient group) need further improvement in postoperative care. Because of small numbers in some operation groups this qualitative evaluation of the postoperative pain and PONV management only gives an approximate overview. The results of QUIPSi uncovered gaps in the postoperative pain management which will help improve the quality in the postoperative setting. The QUIPSi approach should be integrated as a daily tool into all pediatric surgical departments.

Tracheobronchopathia osteochondroplastica: a rare cause of tracheal tube cuff leak.

We present the case of a patient with the rare disorder tracheobronchopathia osteochondroplastica who underwent laparoscopic cholecystectomy. After induction of general anaesthesia, we faced difficulties passing the tracheal tube beyond the vocal cords despite bronchoscopic assistance. With a smaller tube, and by using rotating movements, we managed to successfully intubate the trachea. Because of the irregular tracheal surface, however, ventilation was challenging due to a massive cuff leak. Repeated repositioning did not improve this leak. Only cuff overinflation led to adequate ventilation, though we were cognisant of the increased risk of tracheal wall injury with this approach. After completion of the surgery, the patient's trachea was extubated without complication. This case showed that even with good preparation, intra-operative problems can occur with abnormal subglottic airway anatomy. In some circumstances, these problems can only be solved by compromise. There are no professional consensus or guidelines that can be followed as guiding references for such a case, which can lead to indecisiveness.

Analysis of influenza virus hemagglutinin receptor binding mutants with limited receptor recognition properties and conditional replication characteristics.

To examine the range of selective processes that potentially operate when poorly binding influenza viruses adapt to replicate more efficiently in alternative environments, we passaged a virus containing an attenuating mutation in the hemagglutinin (HA) receptor binding site in mice and characterized the resulting mutants with respect to the structural locations of mutations selected, the replication phenotypes of the viruses, and their binding properties on glycan microarrays. The initial attenuated virus had a tyrosine-to-phenylalanine mutation at HA1 position 98 (Y98F), located in the receptor binding pocket, but viruses that were selected contained second-site pseudoreversion mutations in various structural locations that revealed a range of molecular mechanisms for modulating receptor binding that go beyond the scope that is generally mapped using receptor specificity mutants. A comparison of virus titers in the mouse respiratory tract versus MDCK cells in culture showed that the mutants displayed distinctive replication properties depending on the system, but all were less attenuated in mice than the Y98F virus. An analysis of receptor binding properties confirmed that the initial Y98F virus bound poorly to several different species of erythrocytes, while all mutants reacquired various degrees of hemagglutination activity. Interestingly, both the Y98F virus and pseudoreversion mutants were shown to bind very inefficiently to standard glycan microarrays containing an abundance of binding substrates for most influenza viruses that have been characterized to date, provided by the Consortium for Functional Glycomics. The viruses were also examined on a recently developed microarray containing glycans terminating in sialic acid derivatives, and limited binding to a potentially interesting subset of glycans was revealed. The results are discussed with respect to mechanisms for HA-mediated receptor binding, as well as regarding the species of molecules that may act as receptors for influenza virus on host cell surfaces.