Automatic electrode scalar location assessment after cochlear implantation using a novel imaging software.

As of today, image-based assessment of cochlear implant electrode array location is not part of the clinical routine. Low resolution and contrast of computer tomography (CT) imaging, as well as electrode array artefacts, prevent visibility of intracochlear structures and result in low accuracy in determining location of the electrode array. Further, trauma assessment based on clinical-CT images requires a uniform image-based trauma scaling. Goal of this study was to evaluate the accuracy of a novel imaging software to detect electrode scalar location. Six cadaveric temporal bones were implanted with Advanced Bionics SlimJ and Mid-Scala electrode arrays. Clinical-CT scans were taken pre- and postoperatively. In addition, micro-CTs were taken post-operatively for validation. The electrode scalar location rating done by the software was compared to the rating of two experienced otosurgeons and the micro-CT images. A 3-step electrode scalar location grading scale (0 = electrode in scala tympani, 1 = interaction of electrode with basilar membrane/osseous spiral lamina, 2 = translocation of electrode into scala vestibuli) was introduced for the assessment. The software showed a high sensitivity of 100% and a specificity of 98.7% for rating the electrode location. The correlation between rating methods was strong (kappa > 0.890). The software gives a fast and reliable method of evaluating electrode scalar location for cone beam CT scans. The introduced electrode location grading scale was adapted for assessing clinical CT images.

MR lymphangiography of lymphatic abnormalities in children and adults with Noonan syndrome.

Noonan syndrome is associated with complex lymphatic abnormalities. We report dynamic-contrast enhanced MR lymphangiography (DCMRL) findings in children and adults with Noonan syndrome to further elucidate this complex disease spectrum. A retrospective evaluation of patients with confirmed Noonan syndrome and clinical signs of lymphatic dysfunction undergoing DCMRL between 01/2019 and 04/2021 was performed. MRL included T2-weighted imaging (T2w) and DCMRL. Clinical history/presentation and genetic variants were recorded. T2w-imaging was evaluated for central lymphatic abnormalities and edema distribution. DCMRL was evaluated regarding the presence of cisterna chyli/thoracic duct, lymphatic leakages, pathological lymphatic reflux and abnormal lymphatic perfusion. The time from start of contrast-injection to initial enhancement of the thoracic duct venous junction was measured to calculate the speed of contrast propagation. Eleven patients with Noonan syndrome with lymphatic abnormalities (5 female, 6 male; 7 infants, 4 adults; mean age 10.8 ± 16.4 years) were identified (PTPN11 n = 5/11 [45.5%], RIT1 n = 5/11 [45.5%], KRAS n = 1/11 [9%]). Patients had a chylothorax (n = 10/11 [91%]) and/or pulmonary lymphangiectasia [dilated pulmonary lymph vessels] (n = 9/11 [82%]). Mediastinal/pulmonary edema was depicted in 9/11 (82%) patients. The thoracic duct (TD) was (partially) absent in 10/11 (91%) cases. DCMRL showed lymphatic reflux into intercostal (n = 11/11 [100%]), mediastinal (n = 9/11 [82%]), peribronchial (n = 8/11 [73%]), peripheral (n = 5/11 [45.5%]) and genital lymphatics (n = 4/11 [36%]). Abnormal pulmonary/pleural lymphatic perfusion was seen in 8/11 patients (73%). At infancy peripheral/genital edema was more prevalent in patients with RIT1 than PTPN11 (n = 3/5 vs. n = 0/5). Compared to patients with PTPN11 who had fast lymphatic enhancement in 4/5 patients, enhancement took markedly longer in 4/5 patients with RIT1-mutations. Thoracic duct dysplasia, intercostal reflux and pulmonary/pleural lymphatic perfusion are characteristic findings in patients with Noonan syndrome presenting with chylothorax and/or pulmonary lymphangiectasia. Central lymphatic flow abnormalities show possible phenotypical differences between PTPN11 and RIT1-mutations.

Ultrasound-guided needle positioning for nodal dynamic contrast-enhanced MR lymphangiography.

The aim of the study was to assess injection needle positioning for contrast-enhanced MR-lymphangiography (MRL) by ultrasound-guided injection of saline-solution. 80 patients (33 male, mean age 43.1 years) were referred for MRL. The injection needle position was assessed by injection of saline-solution. Consecutive lymph node distension was observed on sonography followed by MRL. Transpedal MRL was performed when no inguinal lymph nodes could be identified. The inguinal lymph node detection rate was recorded. MR-lymphangiograms were assessed regarding primary (i.e. enhancement of draining lymph vessels) and secondary technical success (i.e. lymph vessel enhancement after repositioning of the needle). MRL was considered as clinically successful if enhancement of the central lymphatic system and/or a lymphatic pathologies were observed. For a total of 92 MRLs 177 groins were evaluated sonographically. In 171/177 groins (96.6%) lymph nodes were identified. After needle placement lymph node distension was observed in 171/171 cases (100%) on saline injection. MR-contrast injection demonstrated enhancement of draining lymph vessels in 163/171 cases (95.3%). In 6/171 cases (3.5%) in-bore needle retraction lead to lymphatic enhancement. In one patient [2/171 nodes (1.1%)] no lymphatic enhancement was seen despite repeated needle repositioning. Overall contrast application was technically successful in 169/171 cases (98.8%). In the 6 groins in which no nodes were identifiable, transpedal MRL was successful. So overall 91/92 MRLs (98.9%) were clinically successful. No complications were recorded. Confirmation of the needle position for nodal MRL by sonographically controlled saline injection is a reliable technique with a high success rate of MRL.

Upscaling the porosity-permeability relationship of a microporous carbonate for Darcy-scale flow with machine learning.

The permeability of a pore structure is typically described by stochastic representations of its geometrical attributes (e.g. pore-size distribution, porosity, coordination number). Database-driven numerical solvers for large model domains can only accurately predict large-scale flow behavior when they incorporate upscaled descriptions of that structure. The upscaling is particularly challenging for rocks with multimodal porosity structures such as carbonates, where several different type of structures (e.g. micro-porosity, cavities, fractures) are interacting. It is the connectivity both within and between these fundamentally different structures that ultimately controls the porosity-permeability relationship at the larger length scales. Recent advances in machine learning techniques combined with both numerical modelling and informed structural analysis have allowed us to probe the relationship between structure and permeability much more deeply. We have used this integrated approach to tackle the challenge of upscaling multimodal and multiscale porous media. We present a novel method for upscaling multimodal porosity-permeability relationships using machine learning based multivariate structural regression. A micro-CT image of Estaillades limestone was divided into small 603 and 1203 sub-volumes and permeability was computed using the Darcy-Brinkman-Stokes (DBS) model. The microporosity-porosity-permeability relationship from Menke et al. (Earth Arxiv, https://doi.org/10.31223/osf.io/ubg6p , 2019) was used to assign permeability values to the cells containing microporosity. Structural attributes (porosity, phase connectivity, volume fraction, etc.) of each sub-volume were extracted using image analysis tools and then regressed against the solved DBS permeability using an Extra-Trees regression model to derive an upscaled porosity-permeability relationship. Ten test cases of 3603 voxels were then modeled using Darcy-scale flow with this machine learning predicted upscaled porosity-permeability relationship and benchmarked against full DBS simulations, a numerically upscaled Darcy flow model, and a Kozeny-Carman model. All numerical simulations were performed using GeoChemFoam, our in-house open source pore-scale simulator based on OpenFOAM. We found good agreement between the full DBS simulations and both the numerical and machine learning upscaled models, with the machine learning model being 80 times less computationally expensive. The Kozeny-Carman model was a poor predictor of upscaled permeability in all cases.

Menthol stimulates calcium absorption in the rumen but not in the jejunum of sheep.

Stimulation of Ca2+ absorption can counteract hypocalcemia at the onset of lactation. The plant bioactive lipid compound (PBLC) menthol is an agonist for nonselective cation channels of the transient receptor potential (TRP) family. It acutely stimulated Ca2+ absorption in ruminal epithelia of nonadapted animals ex vivo and caused higher plasma Ca2+ concentrations in cows and sheep in vivo. To elucidate the pathway by which menthol feeding increases plasma Ca2+ level, the present study aimed to investigate the long-term dose-dependent effects of dietary menthol-rich PBLC on Ca2+ absorption and mRNA abundances of TRP channels in both rumen and jejunum. Twenty-four growing Suffolk sheep were equally distributed to a Con, PBLC-L, and PBLC-H group, which received 0, 80, and 160 mg/d of a menthol-rich PBLC. After 4 wk, ruminal and jejunal epithelia were analyzed for mRNA abundances of TRPA1, TRPV3, TRPV5-6, and TRPM6-8 genes. The Ca2+ flux rates and electrophysiological properties of epithelia from rumen and mid-jejunum were measured in Ussing chambers in the presence and absence of mucosal Na+. Acute changes in Ca2+ flux rates were measured after mucosal application of 50 µM menthol. Ruminal epithelia had quantifiable transcripts of TRPV3 = TRPM6 >TRPM7 >TRPA1 with no difference among feeding groups. Jejunum had quantifiable transcripts of TRPM7 >TRPA1 ≥ TRPM6 ≥ TRPV6 >TRPV5, where TRPA1, TRPV5, and TRPV6 tended to decrease linearly with increasing PBLC dose. Absorptive net flux of Ca2+ was detected only in the rumen, whereas jejunum showed a high passive permeability to Ca2+. Net flux rates of Ca2+ in the rumen increased in a quadratic manner (highest in PBLC-L animals) and were systematically decreased with the omission of mucosal Na+. Short-circuit current increased in both PBLC feeding groups compared with Con only in the rumen. Acute application of menthol-stimulated mucosal-to-serosal and net Ca2+ flux rates only in ruminal epithelia with higher stimulation in PBLC-fed animals. We conclude that Ca2+ transport is mainly active and transcellular in the rumen. It most likely involves TRPV3 that can be stimulated by menthol. Pre-feeding of menthol-rich PBLC enhances ruminal Ca2+ absorption and sensitizes it to acute stimulation by menthol. By contrast, intestinal Ca2+ absorption is not sensitive to menthol stimulation. Menthol could be used as a tool to enhance ruminal Ca2+ absorption and to prevent hypocalcemia in dairy cows.

Characterization and in vitro evaluation of a vaginal gel containing Lactobacillus crispatus for the prevention of gonorrhea.

The increasing resistance of Neisseria gonorrhoeae to any current antibiotic treatment and the difficulties associated with the use of prevention means such as condom urge the need for alternative methods to prevent this sexually transmitted infection. In this work, a prevention strategy based on the use of a vaginal gel containing Lactobacilli was assessed in vitro. A Lactobacillus crispatus strain (ATCC 33197) was selected based on the published data on its ability to inhibit Neisseria gonorrhoeae. Its probiotic properties were first characterized. Then, a thermo-sensitive hydrogel containing 21.5% of poloxamer 407, 1% of sodium alginate and 9log10 CFU of Lactobacillus crispatus per gel sample (5 g) was developed. The gelation temperature and the rheological characteristics of this formulation appeared suitable for a vaginal administration. Lactobacillus crispatus was viable in the gel for six months although a large amount of the bacteria was not culturable. The ability of Lactobacillus crispatus to inhibit Neisseria gonorrhoeae was still observed with the gel. Such system, thus, appeared promising for the prevention of gonorrhea.

Prevalence of enteroparasitic infections and related hormonal and immunological repercussions that may compromise students' physical performance.

The aim of this study was to evaluate the prevalence of enteroparasitic infections in students and their hormonal and immunological repercussions on physical development. Students of basic education of both sexes were evaluated. Parasitological stool tests were performed using the Hoffman and Kato-Katz methods. The students were divided into two groups: a control group (negative parasitological examination, N=25) and an infected group (positive parasitological test, N=25). Anthropometric variables (height, weight, and BMI), concentrations of hormones (melatonin and cortisol), cytokine/chemokine levels (IL-1ß, IL-6, IL-8, IL-10, IL-12, IL-17 and TNF-α) and physical performance (aerobic capacity, upper- and lower-limb muscle strength and abdominal performance) were evaluated. The prevalence of parasitic infection among the students was 7.98%. No anthropometric differences were observed among the groups. IL-2 and TNF-α levels were higher and IL-8 levels were lower in serum from students who were positive for parasitic infection. Serum from students who were positive for parasitic infection showed higher levels of melatonin than that from parasitenegative students. No differences were observed in cortisol levels. Students who were positive for parasitic infection presented greater lower-limb strength and lower abdominal performance than parasite-negative students. In the parasitic infection group, IL-12 was positively correlated with melatonin. In the parasitic infection group, IL-8 showed a positive correlation with aerobic capacity, while IL-17 and TNF-α showed a positive correlation with abdominal performance. These data suggest that parasitic infections determine the profile of inflammatory cytokines and that melatonin may be involved in the control of this process to minimize tissue damage. Additionally, students' difficulty in practising physical exercises can be an indication of enteroparasitic infection.

Does the range of motion in the bovine interphalangeal joints change with flooring condition? A pilot study using biplane high-speed fluoroscopic kinematography.

This study had 2 objectives. The first objective was to investigate motion patterns and the range of motion of the bovine proximal and distal interphalangeal joints on concrete during the stance phase. The second objective was to determine whether the range of motion and the locomotive stability of the interphalangeal joints differ on concrete and 3 different commercially available rubber mats (Karera, Kura, and Pedikura; Kraiburg Elastik GmbH & Co. KG, Tittmoning, Germany). Biplane high-speed fluoroscopic kinematography (72 ± 2.5 kV and 112.5 ± 12.5 mA, refresh rate 500 frames per second, shutter 0.5 ms) was applied to record 1 stance phase of the right forelimb of 2 Holstein Friesian heifers (15 mo old, 440 ± 10 kg; ± standard deviation) on each flooring. Three-dimensional digital animations were generated with a marker-supported manual animation technique based on the recordings and computer tomographic bone models. The mean maximum range of motion of each of the 4 interphalangeal joints in terms of flexion/extension, abduction/adduction, and internal/external rotation were calculated as well as the mean number of local extrema as a measure of stability during the stance phase. The main degree of freedom in all interphalangeal joints was flexion and extension with a range of motion of 17.7 to 25.9°. The second largest degree of freedom differed between abduction/adduction (7.7-10.0°) and internal/external rotation (6.5-9.6°) depending on the joint. Remarkably, although smaller, these extrasagittal directions still contribute to the overall motion to a considerable degree. In addition, the interphalangeal joints of the lateral digit showed a tendency to move less during the stance phase than their medial counterparts. Comparing concrete to the rubber mats, the interphalangeal joints tend to have to cover a larger range of motion on concrete with the exception of the distal interphalangeal joint in terms of flexion/extension. The unyielding surface of concrete seems to force the flexible parts of the animal-ground-interaction into extended motion. Furthermore, there tends to be more instability in all 3 degrees of freedom in all 4 joints on concrete, implying a greater effort of the soft tissues to achieve a balanced motion. Detailed biomechanical research contributes to the development of adequate flooring systems by evaluating the mechanical strain on claws and joints and working toward lameness prevention and thus animal welfare.

Effect of different flooring types on pressure distribution under the bovine claw - an ex vivo study.

BACKGROUND: Mechanical interactions between hard floorings and the sole of bovine claws can be reasonable to cause traumatic claw lesions. In this ex vivo study, the direct kinetic impact of concrete and three types of rubber mats on the sole of dairy cattle claws was analyzed. In order to apply uniform loads, isolated distal hind limbs of adult Holstein Friesian dairy cows were functionally trimmed according to the Dutch method and attached to a load applicator. Kinetic data were recorded using a thin, foil-based pressure measurement system (Hoof™ System, Tekscan®). RESULTS: On concrete, the load distribution between the lateral and medial claw was less balanced than on the rubber floorings. The loaded area was significantly smaller on concrete (32.2 cm2) compared to all rubber mats (48.3-58.0 cm2). Average pressures (Pav) and maximum pressures (Pmax) were significantly higher on concrete (Pav 44.7 N/cm2; Pmax 130.3 N/cm2) compared to the rubber floorings (Pav 24.9-29.7 N/cm2; Pmax 71.9-87.2 N/cm2). Pressure peaks occurred mainly in plantar and abaxial parts of the lateral claw and in apical and plantar regions of the medial claw. Load distribution displayed a widely unloaded slope region, but considering the pressure distribution under the claw, none of the zones showed a generally lower pressure exposure. CONCLUSIONS: Altogether, rubber floorings lead to a significant mechanical relief of the sole compared to concrete. Furthermore, relevant differences between the tested rubber mats could be determined. Therefore the used system may be applied to compare further flooring types.

Validation of biplane high-speed fluoroscopy combined with two different noninvasive tracking methodologies for measuring in vivo distal limb kinematics of the horse.

REASON FOR PERFORMING STUDY: Biplane high-speed fluoroscopy is a new method for gait analysis of the equine distal extremity. This is the first study validating the noninvasive tracking possibilities (Autoscoping and Scientific Rotoscoping) taking equine anatomy into account. OBJECTIVES: To determine the resolution with which Autoscoping and Scientific Rotoscoping depict motion of the equine phalanges in comparison to the invasive gold standard marker-based registration. STUDY DESIGN: Comparative ex vivo study. METHODS: In 5 distal extremities of slaughtered ponies, 3 or 4 tantalum beads with 1 mm diameter were implanted in each of the proximal, middle and distal phalangeal bones. Three-dimensional models of the bones were reconstructed using computed tomographic data (120 kV, 50 mA, slice thickness 1 mm, increment 0.5). The beads were digitally removed from the bone models. Biplane fluoroscopic videos were taken at 69.5 ± 3.5 kV, 102.5 ± 22.5 mA, 500 frames/s and 0.5 ms shutter speed. The 5 specimens were moved in the trial field of the biplane fluoroscopic setup in a step-like motion (simulation of landing, main stance phase, lift-off). Marker-based registration, Autoscoping and Scientific Rotoscoping were carried out. For statistical analysis agreement was computed as percentiles, mean and s.d. RESULTS: The medians of Scientific Rotoscoping ranged from 0.16 to 0.66 mm in translations and 0.43 to 2.78° in rotations, while values for Autoscoping were 0.13-0.70 mm and 0.28-2.39° respectively. With 2 exceptions, all differences between methods were statistically significant. Scientific Rotoscoping is more time efficient than Autoscoping and results in smaller maximum errors. MAIN LIMITATIONS: The experimental set-up was specifically designed to accommodate in vivo requirements. Autoscoping was not manually corrected but rather expected to work automatically. CONCLUSIONS: It is possible to noninvasively apply both Autoscoping and Scientific Rotoscoping for gait analysis of the equine phalanges with high precision. The summary is available in Chinese - see supporting information.

Validation of 2 noninvasive, markerless reconstruction techniques in biplane high-speed fluoroscopy for 3-dimensional research of bovine distal limb kinematics.

Lameness severely impairs cattle's locomotion, and it is among the most important threats to animal welfare, performance, and productivity in the modern dairy industry. However, insight into the pathological alterations of claw biomechanics leading to lameness and an understanding of the biomechanics behind development of claw lesions causing lameness are limited. Biplane high-speed fluoroscopic kinematography is a new approach for the analysis of skeletal motion. Biplane high-speed videos in combination with bone scans can be used for 3-dimensional (3D) animations of bones moving in 3D space. The gold standard, marker-based animation, requires implantation of radio-opaque markers into bones, which impairs the practicability for lameness research in live animals. Therefore, the purpose of this study was to evaluate the comparative accuracy of 2 noninvasive, markerless animation techniques (semi-automatic and manual) in 3D animation of the bovine distal limb. Tantalum markers were implanted into each of the distal, middle, and proximal phalanges of 5 isolated bovine distal forelimbs, and biplane high-speed x-ray videos of each limb were recorded to capture the simulation of one step. The limbs were scanned by computed tomography to create bone models of the 6 digital bones, and 3D animation of the bones' movements were subsequently reconstructed using the marker-based, the semi-automatic, and the manual animation techniques. Manual animation translational bias and precision varied from 0.63 ± 0.26 mm to 0.80 ± 0.49 mm, and rotational bias and precision ranged from 2.41 ± 1.43° to 6.75 ± 4.67°. Semi-automatic translational values for bias and precision ranged from 1.26 ± 1.28 mm to 2.75 ± 2.17 mm, and rotational values varied from 3.81 ± 2.78° to 11.7 ± 8.11°. In our study, we demonstrated the successful application of biplane high-speed fluoroscopic kinematography to gait analysis of bovine distal limb. Using the manual animation technique, kinematics can be measured with sub-millimeter accuracy without the need for invasive marker implantation.

[Dyspnoea after complication-free tracheostomy]. / Atemnot nach komplikationsloser Tracheotomie.

HISTORY: A 70-year-old woman had been under oncological supervision for several years because of breast cancer with bone and lymph node metastases. For several weeks she had been treated for increasing vocal cord paresis of uncertain cause, requiring a tracheostomy, a speech cannula being inserted after eight days. Several days later the patient began to complain of dyspnea, but repeated inspection and cleaning of the cannula failed to reveal its cause. The increasingly anxious patient was given a benzodiazepine preparation to calm her. She was then transferred to the intensive care unit because of worsening respiratory insufficiency and impaired consciousness. DIAGNOSIS AND COURSE: A fiberoptic bronchoscopy was performed immediately, which revealed a black foreign body immediately distal to the tip of the tracheal cannula. The cannula was removed and the slightly sedated patient at once coughed up a large amount of bronchial secretion and a long, curved and fairly firm blood clot. Control bronchoscopy now revealed a flat, slightly hemorrhagic ulcer on the dorsal tracheal wall at the point where the cannula tip had made contact with the tracheal wall. CONCLUSION: Even trained personnel may have difficulty in recognizing intratracheal thrombi in patients with a tracheostomy. It is thus essential that an endoscopy is performed in patients with obstructive symptoms after a tracheostomy.

[Biphasic mesothelioma in a Swiss Braunvieh cow: clinical, histological, immunohistochemical and electron microscopical findings]. / Biphasisches Mesotheliom bei einer Braunviehkuh: Klinische, histomorphologische, immunhistochemische und elektronenmikroskopische Befunde.

A 10-year-old Swiss Braunvieh cow near term was referred to our clinic because of severe abdominal distension, which caused loss of demarcation between the udder and ventral abdominal wall. Ultrasonographic examination revealed marked ascites and multiple echogenic nodules in the greater omentum. Based on the findings, non-inflammatory ascites attributable to neoplasia was diagnosed. Rupture of the prepubic tendon from the pubic symphysis was also suspected. Because of a grave prognosis, parturition was induced and a live calf was delivered. The cow was euthanized and a postmortem examination was carried out. The abdominal cavity contained 248.5 litres of clear fluid. The greater omentum was thickened and oedematous and regionally contained fluid-filled cystic structures, which varied in size with a maximum diameter of 10 centimetres. Based on the histological, immunohistochemical and electron microscopical findings, biphasic mesothelioma with cyst formation affecting the entire abdominal cavity was diagnosed.

Tea catechins' affinity for human cannabinoid receptors.

Among the many known health benefits of tea catechins count anti-inflammatory and neuroprotective activities, as well as effects on the regulation of food intake. Here we address cannabimimetic bioactivity of catechin derivatives occurring in tea leaves as a possible cellular effector of these functionalities. Competitive radioligand binding assays using recombinant human cannabinoid receptors expressed in Chem-1 and CHO cells identified (-)-epigallocatechin-3-O-gallate, EGCG (K(i)=33.6 microM), (-)-epigallocatechin, EGC (K(i)=35.7 microM), and (-)-epicatechin-3-O-gallate, ECG (K(i)=47.3 microM) as ligands with moderate affinity for type 1 cannabinoid receptors, CB1. Binding to CB2 was weaker with inhibition constants exceeding 50 microM for EGC and ECG. The epimers (+)-catechin and (-)-epicatechin exhibited negligible affinities for both CB1 and CB2. It can be concluded that central nervous cannabinoid receptors may be targeted by selected tea catechins but signaling via peripheral type receptors is less likely to play a major role in vivo.

[Despite all--do we have an appropriate substitute for amalgam?].

The ultimate success or failure of a restored tooth is largely dependent on clinical management. Clinicians may choose from a number of restorative materials, different clinical techniques and cavity preparation procedures. Composite resin has been used for nearly 50 years as a restorative material in dentistry. The use of this material has recently increased as a result of patients' demands for esthetic restorations. Failure of dental restorations is a major concern in dental practice. Replacement of failed restorations constitutes the majority of operative work. Clinicians should be aware of the longevity of, and likely reasons for the failure of, direct posterior restorations. Higher failure rates were observed in resin-based composite restorations as compares amalgam restorations. Secondary caries was the main reason for failure. Posterior interproximal resin-based composite restorations should be considered with caution, and their limited long-term performance should be kept in mind. Patients should be informed about the potential longevity of restorative treatment for posterior teeth as they make decisions about treatment for their oral restorative needs.

Immuno-epidemiology of Schistosoma mansoni infections in endemic populations co-infected with soil-transmitted helminths: present knowledge, challenges, and the need for further studies.

This article reviews studies on epidemiological and immunological interactions between Schistosoma mansoni and soil-transmitted helminths (STH) in co-infected patients from endemic areas. In Brazil, co-infections with schistosomes and intestinal nematodes, such as Ascaris lumbricoides, Trichuris trichiura and the hookworms, are still common, especially in poor rural areas. Important factors in the co-occurrence of different helminth species are favorable environmental conditions supporting intermediate hosts and the survival of larval stages outside the human host, widespread poverty, and low levels of hygiene and sanitation. The few existing epidemiological surveys on helminth co-infections in humans indicate positive associations between schistosomes and STH, which means high prevalences of mixed infections, as well as higher intensities of infection in co-infected patients. However, these positive interactions appear to depend on the number of different helminth species present and on the intensity of infection in each individual. For the humoral immune response in co-infected patients, much cross-reactivity in antibody responses against antigenic preparations from schistosomes and STH is observed. Data on cellular immune responses in multiply infected patients are still scarce and additive effects on the cellular reactivity and the down-modulation of cytokines are proposed.

Structure of eukaryotic RNA polymerases.

The eukaryotic RNA polymerases Pol I, Pol II, and Pol III are the central multiprotein machines that synthesize ribosomal, messenger, and transfer RNA, respectively. Here we provide a catalog of available structural information for these three enzymes. Most structural data have been accumulated for Pol II and its functional complexes. These studies have provided insights into many aspects of the transcription mechanism, including initiation at promoter DNA, elongation of the mRNA chain, tunability of the polymerase active site, which supports RNA synthesis and cleavage, and the response of Pol II to DNA lesions. Detailed structural studies of Pol I and Pol III were reported recently and showed that the active center region and core enzymes are similar to Pol II and that strong structural differences on the surfaces account for gene class-specific functions.

Breakthrough infection of Trichosporon asahii during posaconazole treatment in a patient with acute myeloid leukaemia.

A neutropenic patient with acute myeloid leukaemia experienced a breakthrough infection of Trichosporon asahii during posaconazole treatment. After treatment was changed to a combination therapy with voriconazole and liposomal amphotericin B, the infection resolved. Posaconazole works effectively as an antifungal prophylaxis and salvage therapy in rare invasive fungal infections. This case however illustrates that breakthrough infections with T. asahii may occur during posaconazole treatment.

Stage-specific immune responses in human Necator americanus infection.

We describe how hookworms interact with their human hosts by comparing lymphocyte phenotyping, proliferative responses, and cytokine and chemokine secretion patterns in adults who are either mono-infected with Necator americanus or egg-negative controls resident in an area of high transmission in Brazil. Cellular immune responses against crude hookworm antigen extracts from different developmental stages were evaluated simultaneously. Principal component analysis (PCA) was used to reduce the standardized immune responses. Random effects multivariate regression was then used to investigate whether principal components (PC) differ between the two groups once potential confounders and effect modifiers have been accounted for. Although hookworm patients had reduced percentages of T and B cells, they had higher levels of activated CD4(+) T and CD19(+) B cells. This state of 'immune activation' coincided with lower proliferative responses, especially to third-stage larval antigen. Cytokine levels in mono-infected adults were also lower and characterized by a mixed Th1/Th2-type profile. Excretory/secretory antigen from adult worms was a potent modulator of the immune response, resulting in diminished TNF-alpha and IL-10 secretion in peripheral blood mononuclear cells (PBMC) from hookworm infected patients. We propose that the longevity of hookworms in their human hosts results from a stage-specific, down-modulation of the immune response.