Time Trends in Causes of Death in People With HIV: Insights From the Swiss HIV Cohort Study.

BACKGROUND: Advancements in access to antiretroviral therapy (ART) and human immunodeficiency virus (HIV) care have led to a decline in AIDS-related deaths among people with HIV (PWH) in Switzerland. However, data on the ongoing changes in causes of death among PWH over the past 15 years are scarce. METHODS: We investigated all reported deaths in the Swiss HIV Cohort Study between 2005 and 2022. Causes of death were categorized using the Coding Causes of Death in HIV protocol. The statistical analysis included demographic stratification to identify time trends and logistic regression models to determine associated factors for the underlying cause of death. RESULTS: In total, 1630 deaths were reported, with 23.7% of individuals assigned female sex at birth. These deaths included 147 (9.0%) HIV/AIDS-related deaths, 373 (22.9%) due to non-AIDS, non-hepatic cancers, 166 (10.2%) liver-related deaths, and 158 (9.7%) cardiovascular-related deaths. The median age at death (interquartile range) increased from 45.0 (40.0-53.0) years in 2005-2007 to 61.0 (56.0-69.5) years in 2020-2022. HIV/AIDS- and liver-related deaths decreased, whereas deaths from non-AIDS, non-hepatic cancers increased and cardiovascular-related deaths remained relatively stable. CONCLUSIONS: The proportionally decreasing HIV/AIDS and liver-related deaths showcase the effectiveness of ART, comprehensive HIV patient care, and interventions targeting hepatitis C virus coinfection. Future research should focus on managing cancer and cardiovascular-related conditions as the new leading causes of death among PWH. Comprehensive healthcare strategies focusing on non-AIDS-related comorbid conditions, cancer management, and sustaining liver and cardiovascular health are needed to bridge the ongoing health disparities between PWH and the general population.

Blind Spot: A Braille Patterned Novel Multiplex Lateral Flow Immunoassay Sensor Array for the Detection of Biothreat Agents.

Lateral flow immunoassays (LFIs) are simple, point-of-care diagnostic devices used for detecting biological agents or other analytes of interest in a sample. LFIs are predominantly singleplex assays, interrogating one target analyte at a time. There is a need for multiplex LFI devices, e.g., a syndromic panel to differentiate pathogens causing diseases exhibiting similar symptoms. Multiplex LFI devices would be especially valuable in instances where sample quantity is limiting and reducing assay time and costs is critical. There are limitations to the design parameters and performance characteristics of a multiplex LFI assay with many horizontal test lines due to constraints in capillary flow dynamics. To address some of the performance issues, we have developed a spot array multiplex LFI using Braille format (hence called Blind Spot) and a sensor, MACAW (Modular Automated Colorimetric Analyses Widget), that can analyze and interpret the results. As a proof of concept, we created a multiplex toxin panel, for detecting three toxins, using two letter codes for each. The results indicated that the six-plex, triple toxin assay performs as well as singleplex assays. The sensor-based calls are better compared to human interpretation in discriminating and interpreting ambiguous test results correctly especially at lower antigen concentrations and from strips with blemishes.

Single-Domain Antibodies for the Detection of SARS-CoV-2 Nucleocapsid Protein.

The goal of this work was to develop recombinantly expressed variable domains derived from camelid heavy-chain antibodies known as single-domain antibodies (sdAbs) directed against the SARS-CoV-2 nucleocapsid protein for incorporation into detection assays. To achieve this, a llama was immunized using a recombinant SARS-CoV-2 nucleocapsid protein and an immune phage-display library of variable domains was developed. The sdAbs selected from this library segregated into five distinct sequence families. Three of these families bind to unique epitopes with high affinity, low nM to sub-nM KD, as determined by surface plasmon resonance. To further enhance the utility of these sdAbs for the detection of nucleocapsid protein, homobivalent and heterobivalent genetic fusion constructs of the three high-affinity sdAbs were prepared. The effectiveness of the sdAbs for the detection of nucleocapsid protein was evaluated using MagPlex fluid array assays, a multiplexed immunoassay on color-coded magnetic microspheres. Using the optimal bivalent pair, one immobilized on the microsphere and the other serving as the biotinylated recognition reagent, a detection limit as low as 50 pg/mL of recombinant nucleocapsid and of killed virus down to 1.28 × 103 pfu/mL was achieved. The sdAbs described here represent immune reagents that can be tailored to be optimized for a number of detection platforms and may one day aid in the detection of SARS-CoV-2 to assist in controlling the current pandemic.

Antarctic Futures: An Assessment of Climate-Driven Changes in Ecosystem Structure, Function, and Service Provisioning in the Southern Ocean.

In this article, we analyze the impacts of climate change on Antarctic marine ecosystems. Observations demonstrate large-scale changes in the physical variables and circulation of the Southern Ocean driven by warming, stratospheric ozone depletion, and a positive Southern Annular Mode. Alterations in the physical environment are driving change through all levels of Antarctic marine food webs, which differ regionally. The distributions of key species, such as Antarctic krill, are also changing. Differential responses among predators reflect differences in species ecology. The impacts of climate change on Antarctic biodiversity will likely vary for different communities and depend on species range. Coastal communities and those of sub-Antarctic islands, especially range-restricted endemic communities, will likely suffer the greatest negative consequences of climate change. Simultaneously, ecosystem services in the Southern Ocean will likely increase. Such decoupling of ecosystem services and endemic species will require consideration in the management of human activities such as fishing in Antarctic marine ecosystems.

Continuous pH monitoring in wounds using a composite indicator dressing - A feasibility study.

PURPOSE: Modern burn care strives for new means to guarantee optimised wound healing. Several studies have shown a correlation between the pH value in a (burn) wound and successful wound healing. A multitude of devices to monitor pH is available, all requiring direct wound contact and removal of the dressing for pH monitoring. The aim of this feasibility study was to create a sterile and easy to handle method for pH monitoring while simultaneously using an advanced wound dressing. MATERIALS AND METHODS: Dressing sheets of biotechnologically generated nanofibrillar cellulose (epicitehydro) were chemically functionalised with the indicator dye GJM-534. pH-donors with increasing pH were subsequently applied to the created indicator dressing. To investigate temporal resolution and continuous monitoring we used circular pH-donors with different pH (7 and 10) and decreasing diameters that were placed on another dressing sheet. Clinically relevant spatial resolution was checked by a wound bed simulation with small areas (8 mm) of higher pH (10) on a field of lower pH (7) and vice versa. RESULTS: The indicator dressing showed a gradual colouring from yellow to dark orange with increasing pH in steps of 0.3. After conversion of digital pictures to greyscale values, a sigmoidal distribution with a pKa-value of 8.4 was obtained. A ring-like pattern with alternating colour change corresponding to the pH was observed in the continuous monitoring experiment and the wound bed simulation delivered excellent local resolution. CONCLUSION: Since the pH of a (burn) wound can have a significant influence on wound healing, a pH indicator was successfully linked to an advanced, temporary, alloplastic wound dressing material. We were able to show the possibility of pH monitoring by the dressing itself. Additional testing, including studies with large case numbers for optimisation are necessary before clinical implementation.

Sensitive detection of live Escherichia coli by bacteriophage amplification-coupled immunoassay on the Luminex® MAGPIX instrument.

Phages are natural predators of bacteria and have been exploited in bacterial detection because of their exquisite specificity to their cognate bacterial hosts. In this study, we present a "proof of concept" bacteriophage amplification-coupled assay as a surrogate for detecting a bacterium present in a sample. The assay entails detection of progeny phage resulting from infection and subsequent growth inside the bacterium present in suspected samples. This approach reduces testing time and enhances sensitivity to identify pathogens compared to traditional overnight plaque assay. Further, the assay has the ability to discriminate between live and dead cells since phages require live host cells to infect and replicate. To demonstrate its utility, phage MS2 amplification-coupled, bead-based sandwich type immunoassay on the Luminex® MAGPIX instrument for Escherichia coli detection was performed. The assay not only showed live cell discrimination ability but also a limit of E. coli detection of 1 × 102 cells/mL of live cells after a 3-h incubation. In addition, the sensitivity of the assay was not impaired in the presence of dead cells. These results demonstrate that bacteriophage amplification-coupled assay can be a rapid live cell detection assay compared to traditional culture methods and a promising tool for quick validation of bacterial inactivation. Combined with the unique multiplex bead chemistry of the Luminex® MAGPIX platform, the phage assay can be expanded to be an ultra-deep multiplex assay for the simultaneous detection of multiple pathogens using specific phages directed against the target pathogens.

Chalcogenide substitution in the [2Fe] cluster of [FeFe]-hydrogenases conserves high enzymatic activity.

[FeFe]-Hydrogenases efficiently catalyze the uptake and evolution of H2 due to the presence of an inorganic [6Fe-6S]-cofactor (H-cluster). This cofactor is comprised of a [4Fe-4S] cluster coupled to a unique [2Fe] cluster where the catalytic turnover of H2/H+ takes place. We herein report on the synthesis of a selenium substituted [2Fe] cluster [Fe2{µ(SeCH2)2NH}(CO)4(CN)2]2- (ADSe) and its successful in vitro integration into the native protein scaffold of [FeFe]-hydrogenases HydA1 from Chlamydomonas reinhardtii and CpI from Clostridium pasteurianum yielding fully active enzymes (HydA1-ADSe and CpI-ADSe). FT-IR spectroscopy and X-ray structure analysis confirmed the presence of structurally intact ADSe at the active site. Electrochemical assays reveal that the selenium containing enzymes are more biased towards hydrogen production than their native counterparts. In contrast to previous chalcogenide exchange studies, the S to Se exchange herein is not based on a simple reconstitution approach using ionic cluster constituents but on the in vitro maturation with a pre-synthesized selenium-containing [2Fe] mimic. The combination of biological and chemical methods allowed for the creation of a novel [FeFe]-hydrogenase with a [2Fe2Se]-active site which confers individual catalytic features.

Understanding the structure and functioning of polar pelagic ecosystems to predict the impacts of change.

The determinants of the structure, functioning and resilience of pelagic ecosystems across most of the polar regions are not well known. Improved understanding is essential for assessing the value of biodiversity and predicting the effects of change (including in biodiversity) on these ecosystems and the services they maintain. Here we focus on the trophic interactions that underpin ecosystem structure, developing comparative analyses of how polar pelagic food webs vary in relation to the environment. We highlight that there is not a singular, generic Arctic or Antarctic pelagic food web, and, although there are characteristic pathways of energy flow dominated by a small number of species, alternative routes are important for maintaining energy transfer and resilience. These more complex routes cannot, however, provide the same rate of energy flow to highest trophic-level species. Food-web structure may be similar in different regions, but the individual species that dominate mid-trophic levels vary across polar regions. The characteristics (traits) of these species are also different and these differences influence a range of food-web processes. Low functional redundancy at key trophic levels makes these ecosystems particularly sensitive to change. To develop models for projecting responses of polar ecosystems to future environmental change, we propose a conceptual framework that links the life histories of pelagic species and the structure of polar food webs.

A structural view of synthetic cofactor integration into [FeFe]-hydrogenases.

[FeFe]-hydrogenases are nature's fastest catalysts for the evolution or oxidation of hydrogen. Numerous synthetic model complexes for the [2Fe] subcluster (2FeH) of their active site are known, but so far none of these could compete with the enzymes. The complex Fe2[µ-(SCH2)2X](CN)2(CO)42- with X = NH was shown to integrate into the apo-form of [FeFe]-hydrogenases to yield a fully active enzyme. Here we report the first crystal structures of the apo-form of the bacterial [FeFe]-hydrogenase CpI from Clostridium pasteurianum at 1.60 Å and the active semisynthetic enzyme, CpIADT, at 1.63 Å. The structures illustrate the significant changes in ligand coordination upon integration and activation of the [2Fe] complex. These changes are induced by a rigid 2FeH cavity as revealed by the structure of apoCpI, which is remarkably similar to CpIADT. Additionally we present the high resolution crystal structures of the semisynthetic bacterial [FeFe]-hydrogenases CpIPDT (X = CH2), CpIODT (X = O) and CpISDT (X = S) with changes in the headgroup of the dithiolate bridge in the 2FeH cofactor. The structures of these inactive enzymes demonstrate that the 2FeH-subcluster and its protein environment remain largely unchanged when compared to the active enzyme CpIADT. As the active site shows an open coordination site in all structures, the absence of catalytic activity is probably not caused by steric obstruction. This demonstrates that the chemical properties of the dithiolate bridge are essential for enzyme activity.

Interpersonal stroking touch is targeted to C tactile afferent activation.

C tactile fibers are a specialized group of fibers innervating the non-glabrous skin that are tuned to light gentle stroking applied with velocities between 1 and 10 cm/s. Those fibers add to the sensation of interpersonal caressing and pleasant touch. It is unclear whether people spontaneously apply touch that is tuned to optimally activate those fibers. This was investigated in three studies. In study one, 45 participants (21.8 ± 2.3 years, 24 women) were asked to stroke an artificial arm. In study two, 32 participants (28.3 ± 8.7 years, 16 women) were asked to stroke their partner. In study three, 11 parents (29.4 ± 5.7 years, 6 women) were asked to stroke their babies. Stroking velocity was tracked in all conditions. Stroking velocities were significantly slower in the partner touch and baby touch condition than in the artificial arm condition and all of the participants stroking their partner or baby used velocities that can activate C tactile fibers. We conclude that human social stroking is optimized for C tactile stimulation.

Some Remarks on Imaging of the Inner Ear: Options and Limitations.

The temporal bone has a highly complex anatomical structure, in which the sensory organs of the cochlea and the vestibular system are contained within a small space together with the sound-conducting system of the middle ear. Detailed imaging is thus required in this anatomical area. There are a great many clinical aims for which the highest-possible spatial resolution is required. These include the localization of cerebrospinal fluid fistulas, the detection of malformations of the middle and inner ear and the vestibulocochlear nerve, an aberrant course of the facial nerve and anomalies of the arterial and venous structures, the confirmation of dehiscence of the semicircular canals and finally, the verification of endolymphatic hydrops in cases of Ménière's disease. However, the term 'high resolution' is very time dependent. Two milestones in this respect have been (in 1991) the 3D visualization of the inner ear by means of maximum-intensity projection (MIP) of a T2-weighted constructive interference in steady state (CISS) sequence of a 1.5-tesla magnetic resonance imaging (MRI) scanner (Tanioka et al., Radiology 178:141-144, 1991) and (in 1997) imaging of the vestibulocochlear nerve for the diagnosis of hypoplasia inside the internal auditory canal using the same sequence (Casselman et al., Radiology 202:773-781, 1997).The objective of this article is to highlight the options for, and the challenges of, contemporary imaging with regard to some clinical issues relating to the inner ear.

Artifacts in orthodontic bracket systems in cone-beam computed tomography and multislice computed tomography.

OBJECTIVES: The purpose of this study was to quantify artifacts caused by different bracket systems in cone-beam computed tomography (CBCT) and multislice computed tomography (MSCT) scans. METHODS: Orthodontic brackets of four different systems were consecutively bonded to the surface of a residual molar on a human cadaveric mandible. One MSCT system and three CBCT units were used to scan each of the four bonded brackets, in addition to obtaining a blank reference scan of the tooth surface. All datasets were registered to the reference dataset using visualization software (Analyze 11.0® by AnalyzeDirect). Artifact-related reductions in image quality were expressed in percent of theoretical maximum standard deviations (SD) obtained for the gray values of the adjacent voxels, with higher percentages correlating more pronounced artifacts. RESULTS: Both the SD percentages for three defined line profiles and their mean values were almost invariably higher with the MSCT system than with the CBCT units. Looking into the individual SD percentages, two of the CBCT units (Pax Zenith 3D® and Picasso Trio®; both Vatech) produced higher values than the MSCT system (SOMATOM Definition AS+®; Siemens) in some line profiles. The titanium bracket, in particular, was associated with marked differences between the two scanner technologies, as the mean artifact intensities from this bracket were particularly high with the MSCT unit and relatively low with the CBCT units. The artifact intensities observed with the other three bracket systems varied widely depending on which scanner was used. CONCLUSION: Different artifact intensities were noted depending on the composition of the bracket system and on the scanner technology (MSCT/CBCT). While the artifacts manifested themselves differently with different scanners, their adverse effects were comparable. However, given the variable severity of the artifacts observed depending on the materials scanned and the scanners used, a blanket recommendation for or against MSCT or CBCT units cannot be given on the basis of this study.

Imaging the Parasinus Region with a Third-Generation Dual-Source CT and the Effect of Tin Filtration on Image Quality and Radiation Dose.

BACKGROUND AND PURPOSE: CT is the imaging technique of choice in the evaluation of midface trauma or inflammatory disease. We performed a systematic evaluation of scan protocols to optimize image quality and radiation exposure on third-generation dual-source CT. MATERIALS AND METHODS: CT protocols with different tube voltage (70-150 kV), current (25-300 reference mAs), prefiltration, pitch value, and rotation time were systematically evaluated. All images were reconstructed with iterative reconstruction (Advanced Modeled Iterative Reconstruction, level 2). To individually compare results with otherwise identical factors, we obtained all scans on a frozen human head. Conebeam CT was performed for image quality and dose comparison with multidetector row CT. Delineation of important anatomic structures and incidental pathologic conditions in the cadaver head was evaluated. RESULTS: One hundred kilovolts with tin prefiltration demonstrated the best compromise between dose and image quality. The most dose-effective combination for trauma imaging was Sn100 kV/250 mAs (volume CT dose index, 2.02 mGy), and for preoperative sinus surgery planning, Sn100 kV/150 mAs (volume CT dose index, 1.22 mGy). "Sn" indicates an additional prefiltration of the x-ray beam with a tin filter to constrict the energy spectrum. Exclusion of sinonasal disease was possible with even a lower dose by using Sn100 kV/25 mAs (volume CT dose index, 0.2 mGy). CONCLUSIONS: High image quality at very low dose levels can be achieved by using a Sn100-kV protocol with iterative reconstruction. The effective dose is comparable with that of conventional radiography, and the high image quality at even lower radiation exposure favors multidetector row CT over conebeam CT.

Cone beam computed tomography and low-dose multislice computed tomography in orthodontics and dentistry: a comparative evaluation on image quality and radiation exposure.

OBJECTIVES: The goal of the present work was to assess various computed tomography (CT) systems in term of image quality and organ doses, namely five cone-beam CT (CBCT) scanners operated at standard settings and three multislice CT (MSCT) scanners operated at greatly dose-reduced settings. MATERIALS AND METHODS: Radiographic volume scans were taken on a complete human cadaveric head specimen and the image quality of each was rated by four experienced examiners according to specific skeletal structures and bone-soft tissue interfaces. Radiation doses were captured by a head-and-neck phantom (Rando; Alderson Research Laboratories). Standard protocols were used for the CBCT scans. For the MSCT scans, tube voltage and current were adjusted to minimize radiation without compromising image quality. RESULTS: Interobserver agreement was close to perfect, with iota coefficients of 0.931 (95% CI 0.807-0.978) between groups 1 and 2 and 0.959 (95% CI 0.869-1.000) between groups 1 and 3. Ratings of image quality in terms of skeletal-structure representation were slightly better for the CBCT than the MSCT scanners, although these differences were not statistically significant. The two groups of scanners applied considerably different organ doses: the lowest dose (0.03 mSv) was measured on the bone surface with a CBCT unit (Picasso Trio® from Vatech) and the highest dose (8.30 mSv) in the vicinity of the eye lens with another CBCT unit (3D Accuitomo 170® from J. Morita). CONCLUSION: The various systems tested offer similar imaging quality but demonstrated distinct differences in organ dose levels. The decision on which approach to take is not between CBCT and MSCT but rather between specific models and parameter settings. If these are optimized, MSCT images providing useful clinical information can be obtained at much reduced levels of radiation. Depending on the model and setting used, MSCT radiation levels may even be lower than during CBCT scans.

Metric precision via soft-tissue landmarks in three-dimensional structured-light scans of human faces.

OBJECTIVES: The goal of the current work was to investigate the suitability of ten facial soft-tissue landmarks (trichion, glabella, nasion, left and right orbital, subnasal, left and right porion, pogonion, gnathion) as reference points for metric facial analysis by analyzing their intra- and interserial precision in all three dimensions. METHODS: The faces of 32 volunteers were scanned using a standardized protocol with a structured-light scanner (FaceSCAN(3D) Scientific Photolab 60 Hz; 3D Shape, Erlangen, Germany). Three examiners placed the landmarks twice within a 2-week interval. Image processing (Onyx Ceph(3); Image Instruments; Chemnitz, Germany) and statistical (SAS 9.2; SAS Institute, Cary, NC, USA) software was used for analysis. All measurements were corrected for mean values per patient and analyzed for intraserial and interserial error by model II ANOVA for a simple classification with random effects. RESULTS: Median intraserial precision was 0.40 mm (range 0.05-1.01 mm) overall, including 0.40 mm (0.33-0.85 mm) on the x-axis, 0.64 mm (0.36-0.87 mm) on the y-axis, and 0.27 mm (0.05-1.01 mm) on the z-axis. Interserial precision was substantially lower at a median of 0.05 mm (0-0.22 mm), often not statistically assessable with intraserial precision. We observed no landmark-associated differences; in particular, the medians of the bilateral landmarks orbital (intraserial: 0.40 mm; interserial: 0.02 mm) and porion (intraserial: 0.36 mm; interserial: small and not assessable) were in the middle of the range of our results. Trichion (intraserial: 0.73 mm; interserial: 0.05 mm) and gnathion (intraserial: 0.87 mm; interserial: 0.20 mm) revealed the highest degrees of intraserial measurement imprecision. Outliers were identified in 1.2% (64 of 5400) of measurements. CONCLUSION: All selected landmarks offer suitably high levels of intra- and interserial precision for the three-dimensional (3D) metric assessment of facial soft-tissue parameters. No difference between (bi)lateral and facial midline landmarks was noted.

Prevalence of different forms of infarct-atypical late gadolinium enhancement in patients early and late after heart transplantation.

BACKGROUND: Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) enables high-resolution myocardial tissue characterization, showing the results of different injuries, especially in the early period after heart transplantation (HTX). OBJECTIVES: We sought to apply LGE-CMR to investigate the prevalence and patterns of infarct-atypical myocardial involvement and associated mechanisms in patients early and late after HTX. METHODS: LGE-CMR was performed on a 1.5-T MRI scanner (Philips, Best, the Netherlands) in 89 patients: group 1 (48 patients) less than 2.5 years after operation (1.2 ± 0.5 years) and group 2 (41 patients) later this period (8.2 ± 4.2 years). Following LGE-CMR, the presence, distribution, patterns of infarct-atypical LGE and possible associated mechanisms were assessed. RESULTS: 71 % of group 1 patients (34/48) showed infarctatypical LGE whereas 57 % of group 2 patients (22/41) were affected (p = 0.25). Fewer segments/patients were involved later after HTX (1.6 ± 2.0 vs. 2.9 ± 3.1 segments/ patient; p = 0.03), but only diffuse LGE-CMR pattern decreased significantly (11.5 % of affected segments in group 1 vs. 6.5 % in group 2; p\0.001). Group 2 had lower ischemic time (181 ± 53 vs. 208 ± 61 min; p = 0.03), the donors were younger (33 ± 13 vs. 41 ± 13 years; p = 0.01) and fewer donors were Toxoplasma gondii seropositive (4 vs. 22pts; p\0.001). CONCLUSION: Infarct-atypical LGE was found in a significant number of patients early post-HTX, however, fewer patients and myocardial segments per patient were affected later after HTX. Many potential factors seem to be involved, but the exact mechanisms are still unclear. Future studies are necessary to test prognostic implications associated with LGE-CMR patterns.

Ribosome synthesis and MAPK activity modulate ionizing radiation-induced germ cell apoptosis in Caenorhabditis elegans.

Synthesis of ribosomal RNA by RNA polymerase I (RNA pol I) is an elemental biological process and is key for cellular homeostasis. In a forward genetic screen in C. elegans designed to identify DNA damage-response factors, we isolated a point mutation of RNA pol I, rpoa-2(op259), that leads to altered rRNA synthesis and a concomitant resistance to ionizing radiation (IR)-induced germ cell apoptosis. This weak apoptotic IR response could be phenocopied when interfering with other factors of ribosome synthesis. Surprisingly, despite their resistance to DNA damage, rpoa-2(op259) mutants present a normal CEP-1/p53 response to IR and increased basal CEP-1 activity under normal growth conditions. In parallel, rpoa-2(op259) leads to reduced Ras/MAPK pathway activity, which is required for germ cell progression and physiological germ cell death. Ras/MAPK gain-of-function conditions could rescue the IR response defect in rpoa-2(op259), pointing to a function for Ras/MAPK in modulating DNA damage-induced apoptosis downstream of CEP-1. Our data demonstrate that a single point mutation in an RNA pol I subunit can interfere with multiple key signalling pathways. Ribosome synthesis and growth-factor signalling are perturbed in many cancer cells; such an interplay between basic cellular processes and signalling might be critical for how tumours evolve or respond to treatment.

[Cerebral venous thrombosis and subdural haematoma: complications of spontaneous intracranial hypotension]. / Sinus-/Hirnvenenthrombose und Subduralhämatome als Komplikationen eines spontanen Liquorunterdrucksyndroms.

We report on the case of a spontaneous intracranial hypotension with subdural hygroma, as well as cerebral venous thrombosis (CVT), both known complications of intracranial hypotension. The 45-year-old patient was subsequently treated - according to current guidelines for CVT - with anticoagulation, but developed subdural haematoma (SDH), which required neurosurgical treatment. Our case highlights the complex pathophysiological sequelae of intracranial hypotension, as well as the occasionally difficult treatment decisions. Subdural hygroma probably predisposes patients to SDH during anticoagulation. Thus, the potential benefit of anticoagulation needs to be weighed against the risk of SDH on an individual basis.

Angiography and cerebral perfusion scintigraphy in balloon test occlusion of carotid artery in head and neck tumors.

PURPOSE: Surgery of head and neck tumors and other tumors involving the carotid artery may demand complete sacrifice of the carotid as part of the necessary tumor therapy. Sacrifice of the carotid may result in permanent brain perfusion damage. This uncorrectable procedure has to be tested beforehand in order to exclude this possibility. MATERIALS AND METHODS: In order to predict this possible unstable hemodynamic brain perfusion damage, we evaluated 12 patients with head neck tumors prior to possible sacrifice of the carotid. The following tests were applied: angiography of the neck vessels, balloon test occlusion (BTO) of the carotid lasting 10 minutes combined with perfusion reserve testing using 1000 mg acetazolamide i. v. All patients received brain perfusion scintigraphy SPECT with Tc-99 m HMPAO injected during BTO. RESULTS: All patient data were evaluated for clinical neurological defects under BTO. Perfusion of the great vessels was evaluated semiquantitatively for angiography (filling delay of the ophthalmic artery) and perfusion SPECT. None of the patients suffered from neurological defects. 9 /12 patients showed mild to severe perfusion defects. 9 /12 patients showed filling delays of more than 1 second. Both tests showed a very good correlation (p = 0.005). Only 2 /12 cases were discrepant in one degree. All severe defects were congruent in both tests. CONCLUSION: None of the patients with severe defects underwent sacrifice of the carotid. Both tests resulted in increased security regarding the prediction of possible brain perfusion damage. The combination of angiography and brain scintigraphy is logistically easy and has a high value of prediction.