Right Ventricular Longitudinal Strain Predicts Survival in Patients With Functional Tricuspid Regurgitation

BackgroundFunctional tricuspid regurgitation (TR) is a frequent finding in echocardiography. Despite general consent that right ventricular (RV) dysfunction impacts outcome of patients with TR, it is still unknown which echocardiographic parameters most accurately reflect prognosis. In this study we aimed to evaluate the prevalence of RV dysfunction and its prognostic value in patients with TR.MethodsData from 1089 consecutive patients were analysed. Tricuspid annular plane systolic excursion (TAPSE), fractional area change, and right ventricular free wall longitudinal strain (RV strain) were used to define RV dysfunction. Patients were followed for 2-year all-cause mortality. For prediction of survival, reclassification and C statistics of RV functional parameters using TR grade as reference model were performed.ResultsAmong the patients studied, 13.9% showed no TR, 61.2% had mild TR, 19.6% had moderate TR, and 5.3% had severe TR. The TR grade was associated with increased mortality (log rank, P < 0.001). Impaired RV strain and TAPSE were independent predictors for mortality (RV: hazard ratio [HR], 1.130; 95% confidence interval [CI], 1.099-1.160; P < 0.001; TAPSE: HR, 1.131; 95% CI, 1.085-1.175; P < 0.001). Both RV strain and TAPSE improved the reference model for survival prediction (RV: integrated discrimination improvement [IDI], 0.184; 95% CI, 0.146-0.221; P < 0.001; TAPSE: IDI, 0.057; 95% CI, 0.037-0.077; P < 0.001).ConclusionsEchocardiographic evaluation of RV function appears to useful for patients with TR. Assessment of RV strain provides additional value for prediction of 2-year mortality.     

Eosinophils contribute to IL-4 production and shape the T-helper cytokine profile and inflammatory response in pulmonary cryptococcosis

Susceptibility to infection with Cryptococcus neoformans is tightly determined by production of IL-4. In this study, we investigated the time course of IL-4 production and its innate cellular source in mice infected intranasally with C. neoformans. We show that pulmonary IL-4 production starts surprisingly late after 6 weeks of infection. Interestingly, in the lungs of infected mice, pulmonary T helper (Th) cells and eosinophils produce significant amounts of IL-4. In eosinophil-deficient ΔdblGATA mice, IL-33 receptor-expressing Th2s are significantly reduced, albeit not absent, whereas protective Th1 and Th17 responses are enhanced. In addition, recruitment of pulmonary inflammatory cells during infection with C. neoformans is reduced in the absence of eosinophils. These data expand previous findings emphasizing an exclusively destructive effector function by eosinophilic granulocytes. Moreover, in ΔdblGATA mice, fungal control is slightly enhanced in the lung; however, dissemination of Cryptococcus is not prevented. Therefore, eosinophils play an immunoregulatory role that contributes to Th2-dependent susceptibility in allergic inflammation during bronchopulmonary mycosis.     

Postural control during galvanic vestibular stimulation in patients with persistent perceptual–postural dizziness

Journal of Neurology - Over the past years galvanic vestibular stimulation (GVS) has been increasingly applied to stimulate the vestibular system in health and disease, but not in patients with...     

Expandable endoprosthesis for limb-sparing surgery in children: long-term results

Purpose

Most children today with bone sarcomas undergo limb-sparing surgery. When treating children younger than 12 years of age, the result is significant limb length discrepancy (LLD). One of the solutions is the use of an expandable endoprosthesis.

Methods

A retrospective analysis of 38 skeletally immature patients with bone sarcoma of the lower limb in whom different types of expandable endoprostheses were used from January 1988 to December 2005 were included. All patients were under the age of 14 years. There were 26 osteosarcoma and 12 Ewing’s sarcomas. The data collected included the tumor characteristics, the surgical and other treatment modalities, complications and their treatment, and the final LLD and functional results.

Results

Fifty-five percent of the patients survived and had a mean follow-up of 113 months. All survivors reached skeletal maturity at the time of last follow-up. Seventy-one percent of the survivors had satisfactory function and 29% had a poor result. There were three secondary amputations due to local recurrence. Complications were documented in 58% of patients; the most common was infection that was diagnosed 56 times (primary 16% and secondary 84%). A significant correlation was found between function and final LLD (greater than 5 cm = inferior function), the number of complications, and the number of surgical procedures performed other than prosthesis elongation. The younger the patient was at definitive surgery, the shorter the time it took for the prosthesis to fail.

Conclusion

In order to improve results, the number of operations must be reduced. This can be achieved by the use of novel non-invasive expandable endoprostheses or biological reconstruction.     

Anaerobic methane oxidation coupled to denitrification is the dominant methane sink in a deep lake

Anaerobic methane oxidation coupled to denitrification, also known as “nitrate/nitrite-dependent anaerobic methane oxidation” (n-damo), was discovered in 2006. Since then, only a few studies have identified this process and the associated microorganisms in natural environments. In aquatic sediments, the close proximity of oxygen- and nitrate-consumption zones can mask n-damo as aerobic methane oxidation. We therefore investigated the vertical distribution and the abundance of denitrifying methanotrophs related to Candidatus Methylomirabilis oxyfera with cultivation-independent molecular techniques in the sediments of Lake Constance. Additionally, the vertical distribution of methane oxidation and nitrate consumption zones was inferred from high-resolution microsensor profiles in undisturbed sediment cores. M. oxyfera-like bacteria were virtually absent at shallow-water sites (littoral sediment) and were very abundant at deep-water sites (profundal sediment). In profundal sediment, the vertical distribution of M. oxyfera-like bacteria showed a distinct peak in anoxic layers that coincided with the zone of methane oxidation and nitrate consumption, a strong indication for n-damo carried out by M. oxyfera-like bacteria. Both potential n-damo rates calculated from cell densities (660–4,890 µmol CH₄⋅m⁻²⋅d⁻¹) and actual rates calculated from microsensor profiles (31–437 µmol CH₄⋅m⁻²⋅d⁻¹) were sufficiently high to prevent methane release from profundal sediment solely by this process. Additionally, when nitrate was added to sediment cores exposed to anoxic conditions, the n-damo zone reestablished well below the sediment surface, completely preventing methane release from the sediment. We conclude that the previously overlooked n-damo process can be the major methane sink in stable freshwater environments if nitrate is available in anoxic zones.Freshwater habitats contribute a major part to the global emissions of the important greenhouse gas methane (1). However, most of the methane that is formed in deeper anoxic zones of freshwater habitats (e.g., lake sediments) is oxidized before it reaches the atmosphere (2). This mitigation of freshwater methane emissions was long thought to be carried out solely by aerobic methanotrophic bacteria. After the first indications of anaerobic methane oxidation coupled to denitrification in freshwater habitats based on tracer experiments (3, 4), the discovery, enrichment, and detection of denitrifying methanotrophs (5–10) ultimately has proven that methane oxidation also takes place in anoxic zones of freshwater habitats. The process of anaerobic methane oxidation coupled to denitrification, also called “nitrate/nitrite-dependent anaerobic methane oxidation” (n-damo), is carried out by members of the candidate phylum NC10 (6) and an archaeal lineage related to the anaerobic methanotrophic (ANME) archaea (11). Of four different groups of NC10 bacteria, only group a was enriched and shown to mediate n-damo (7), but group b always was found in the same habitats (7, 12–14). The genome sequence of a group a NC10 bacterium, Candidatus Methylomirabilis oxyfera, led to the experimentally supported assumption that, as in aerobic methanotrophs, methane is oxidized by a methane monooxygenase [encoded by a particulate methane monooxygenase (pmo) gene cluster] via an intriguing intra-aerobic mechanism (15). Although 16S rRNA gene sequences and pmoA gene sequences that allow a functional assignment to a methanotrophic lifestyle appear in public databases, few studies have investigated the distribution and occurrence of these denitrifying methanotrophs in detail. However, a recent study claimed n-damo to be an overlooked methane sink in wetlands (13). M. oxyfera-like bacteria (group a NC10 bacteria) also were investigated in different high-nitrate environments such as wastewater treatment plants (16), a minerotrophic peatland (14), paddy soil (17), and Lake Constance (5). The Lake Constance study suggested a distinct distribution of the n-damo process and M. oxyfera-like bacteria in a nitrate-rich and seasonally stratified lake. In Lake Constance, nitrate concentrations are comparably high because of exogenous inorganic nitrogen input by rivers; nitrate concentrations increased from 30–40 µM in the early 1960s to 60–80 µM in the late 1980s and have remained constant ever since (18). Based on only one sediment core per site, M. oxyfera-like bacteria have been detected in deep-water (profundal) sediment but were absent at a shallow-water (littoral) sediment site. To estimate the contribution of n-damo in mitigating methane emissions from freshwater habitats, more comprehensive data on n-damo rates in different habitats are needed. The n-damo rates have been calculated based on tracer experiments (5, 13), but in situ rates based on methane and nitrate/nitrite distribution gradients have not been calculated so far (13, 14). In the special case of a minerotrophic peatland infused with nitrate-contaminated groundwater, methane apparently was oxidized completely within the anoxic zone (14). Regrettably, in high-turnover environments with high microbial activity, gradients usually are steep, and different substrates are consumed at close spatial proximity, complicating reliable measurements. In the present study, we investigated the NC10 bacterial communities in sediments of various water depths in Lake Constance. In addition, high-resolution microsensor measurements of methane, oxygen, nitrate, and nitrite gradients and anoxic incubations of intact sediment cores were conducted to assess the importance of n-damo in the mitigation of methane emissions from the microbially highly active sediments in this deep lake.     

Thrombopoietin contributes to neuronal damage in experimental bacterial meningitis

Thrombopoietin (Tpo), which primarily regulates megakaryopoiesis, and its receptor (c-Mpl) are expressed in the brain, where Tpo exhibits proapototic effects on neurons. In the present study, we investigated the implication of Tpo in experimental pneumococcal meningitis. Following intrathecal infection with the encapsulated Streptococcus pneumoniae strain D39, we observed upregulation of Tpo mRNA expression at 12 h and 24 h in brain homogenates of wild-type C57BL/6 mice. c-Mpl mRNA expression was upregulated at 12 h and returned to baseline at 24 h. Compared to wild-type mice, mutants with homozygous Tpo receptor ablation (c-Mpl(-/-)) displayed reduced microglial activation and neuronal apoptosis in the dentate gyrus. Concentrations of bacteria in blood or cerebrospinal fluid (CSF), as well as CSF pleocytosis, were not significantly different between wild-type and c-Mpl(-/-) mice. In human postmortem brain, Tpo protein was colocalized to macrophages during encephalitis. In murine primary microglia and RAW264.7 macrophages, upregulation of Tpo mRNA was induced by D39-conditioned medium but not by bacterial lipopeptide or by medium conditioned by pneumococcal mutants defective in hydrogen peroxide formation (ΔspxB) or pneumolysin (Δpln). We conclude that Tpo acts as a mediator of neuronal damage in bacterial meningitis.     

Risk factors associated with an outbreak of COVID-19 in a meat processing plant in southern Germany,April to June 2020

Meat processing plants have been prominent hotspots for coronavirus disease (COVID-19) outbreaks around the world. We describe infection prevention measures and risk factors for infection spread at a meat processing plant in Germany with a COVID-19 outbreak from April to June 2020. We analysed a cohort of all employees and defined cases as employees with either a PCR or ELISA positive result. Of 1,270 employees, 453 (36%) had evidence of SARS-CoV-2 infection. The highest attack rates were observed in meat processing and slaughtering areas. Multivariable analysis revealed that being a subcontracted employee (adjusted risk ratio (aRR)): 1.43, 95% CI: 1.06–1.96), working in the meat cutting area (aRR: 2.44, 95% CI: 1.45–4.48), working in the slaughtering area (aRR: 2.35, 95% CI: 1.32–4.45) and being a veterinary inspector (aRR: 4.77, 95% CI: 1.16–23.68) increased infection risk. Sharing accommodation or transportation were not identified as risk factors for infection. Our results suggest that workplace was the main risk factor for infection spread. These results highlight the importance of implementing preventive measures targeting meat processing plants. Face masks, distancing, staggering breaks, increased hygiene and regular testing for SARS-CoV2 helped limit this outbreak, as the plant remained open throughout the outbreak.     

Bilateral Hypertrophic Olivary Degeneration in Wilson Disease

Hypertrophic olivary degeneration resulting from lesions of the dento-rubro-olivary pathway, also called Guillain-Mollaret-triangle, has been described previously in a number of cases. Reports about bilateral hypertrophic olivary degeneration of the inferior olivary nuclei are very limited, and the magnetic resonance imaging findings of hypertrophic olivary degeneration in Wilson disease have not yet been described to the best of our knowledge. Herein, we present the first report of bilateral hypertrophic olivary degeneration diagnosed by magnetic resonance imaging in a patient suffering from Wilson disease.     

A duck with four legs: Investigating the structure of conceptual knowledge using picture drawing in semantic dementia

In Study 1, six patients with semantic dementia were asked to produce drawings of concrete concepts from dictation of their names. The drawings were characterised by a loss of distinctive features. In the artefact domain, this feature loss resulted in representations that were increasingly box-like. In the living domain, as well as distinctive features being lost, there was a tendency for patients to include incorrect features that resulted in more familiar and "prototypical" representations. A second study included two further conditions in the drawing assessment: immediate and delayed copying of line drawings of concrete concepts. Analysis of the drawings produced by three patients with semantic dementia confirmed that overall performance was significantly influenced by the task condition (immediate delayed) and severity of disease. The rate of intruding features, but not of omitted ones, was influenced by the domain of the item, with a greater proportion of intrusions in the living than in the nonliving domain. There was also a significant effect of feature distinctiveness on the proportions of these error types: Intruded features were most likely to come from the pool of properties that are shared across domain.