Invasive slug Meghimatium pictum (Stoliczka, 1873) infected by Angiostrongylus costaricensis Morera & Céspedes, 1971, and the possible risk of human infection associated with grape consumption.

Many molluscs may be infected with angiostrongylid larvae. Following the histopathological diagnosis of abdominal angiostrongyliasis in a grape farmer from southern Brazil, molluscs in the area were investigated. During a nocturnal search, 245 specimens of slugs were collected and identified as the invasive Chinese slug Meghimatium pictum. Angiostrongylus costaricensis worms were recovered from mice that were experimentally infected with larvae obtained from 11 (4.5%) of the molluscs. This study presents the first report of M. pictum being identified as an intermediate host for A. costaricensis. Most of the slugs were collected from grape plants, which suggests that transmission may be associated with grape consumption.

[Combined convergent elbow dislocation with posterior luxation of the humeroulnar joint and radial head comminuted fracture in adults]. / Kombinierte konvergente Ellenbogenluxation mit posteriorer Luxation des Humeroulnargelenks und Radiuskopftrümmerfraktur beim Erwachsenen.

Transposition of the proximal radioulnar joint, so-called convergent elbow dislocation, is an extremely rare injury whereby the proximal radius crosses over the proximal ulnar and converges medially. This injury can occur in isolation or even less frequently in association with a posterior humeroulnar dislocation. Open reduction is almost always necessary. The diagnosis is frequently delayed as the injury is easily overlooked. In the literature, 13 cases in children and 2 in adults have so far been described. This is the first report of a combined elbow dislocation (posterior and convergent) with an initially diagnosed and definitively treated comminuted radial head fracture in adults.

[Diagnostics and treatment of olfactory dysfunction]. / Diagnostik und Therapie von Riechstörungen.

BACKGROUND: Dysosmia is one of the most common disorders in otorhinolaryngology. However, epidemiological data are lacking and treatment strategies are insufficiently standardized. OBJECTIVE: The aim of this study was to evaluate the frequency of causes of olfactory disorders and the different therapeutic approaches used in ENT departments in German-speaking countries. The results were also compared to findings of the survey in 2000. Furthermore, a systematic review of treatment strategies was conducted. MATERIALS AND METHODS: In 2010, a two-page survey addressing olfactory dysfunction was sent to all ENT departments in German-speaking countries. The literature review included sources such as PubMed, the Cochrane Library, and relevant guidelines. RESULTS: The diagnosis of dysosmia was made less frequently in ENT departments (decrease of 52%). The three most widely used therapeutic approaches were corticosteroids (topical and systemic) and systemic antibiotics. There is evidence in the literature showing a small to medium effect of topical steroids in sinonasal smell disorders. CONCLUSION: Since a 50% decrease in the prevalence of olfactory disturbances is unlikely, the lower patient numbers may relate to a more critical diagnosis. The use of olfactory training in clinics has increased significantly (from <6% to up to 23%). The use of topical steroids for sinonasal dysosmia is evidence based. Smell training is a safe and effective treatment strategy, especially in post-infectious and post-traumatic olfactory disorders.

Detection of ABCB5 tumour antigen-specific CD8+ T cells in melanoma patients and implications for immunotherapy.

ATP binding cassette subfamily B member 5 (ABCB5) has been identified as a tumour-initiating cell marker and is expressed in various malignancies, including melanoma. Moreover, treatment with anti-ABCB5 monoclonal antibodies has been shown to inhibit tumour growth in xenotransplantation models. Therefore, ABCB5 represents a potential target for cancer immunotherapy. However, cellular immune responses against ABCB5 in humans have not been described so far. Here, we investigated whether ABCB5-reactive T cells are present in human melanoma patients and tested the applicability of ABCB5-derived peptides for experimental induction of human T cell responses. Peripheral blood mononuclear cells (PBMNC) isolated from blood samples of melanoma patients (n = 40) were stimulated with ABCB5 peptides, followed by intracellular cytokine staining (ICS) for interferon (IFN)-γ and tumour necrosis factor (TNF)-α. To evaluate immunogenicity of ABCB5 peptides in naive healthy donors, CD8 T cells were co-cultured with ABCB5 antigen-loaded autologous dendritic cells (DC). ABCB5 reactivity in expanded T cells was assessed similarly by ICS. ABCB5-reactive CD8+ T cells were detected ex vivo in 19 of 29 patients, melanoma antigen recognised by T cells (MART-1)-reactive CD8+ T cells in six of 21 patients. In this small, heterogeneous cohort, reactivity against ABCB5 was significantly higher than against MART-1. It occurred significantly more often and independently of clinical characteristics. Reactivity against ABCB5 could be induced in 14 of 16 healthy donors in vitro by repeated stimulation with peptide-loaded autologous DC. As ABCB5-reactive CD8 T cells can be found in the peripheral blood of melanoma patients and an ABCB5-specific response can be induced in vitro in naive donors, ABCB5 could be a new target for immunotherapies in melanoma.

A whole cell biocatalyst for double oxidation of cyclooctane.

A novel whole cell cascade for double oxidation of cyclooctane to cyclooctanone was developed. The one-pot oxidation cascade requires only a minimum of reaction components: resting E. coli cells in aqueous buffered medium (=catalyst), the target substrate and oxygen as environmental friendly oxidant. Conversion of cyclooctane was catalysed with high efficiency (50% yield) and excellent selectivity (>94%) to cyclooctanone. The reported oxidation cascade represents a novel whole cell system for double oxidation of non-activated alkanes including an integrated cofactor regeneration. Notably, two alcohol dehydrogenases from Lactobacillus brevis and from Rhodococcus erythropolis with opposite cofactor selectivities and one monooxygenase P450 BM3 were produced in a coexpression system in one single host. The system represents the most efficient route with a TTN of up to 24363 being a promising process in terms of sustainability as well.

Identification of a new HLA-B*57 allele, HLA-B*57:71, by next-generation sequencing.

The sequence of a novel allele, HLA-B*57:71, differs from HLA-B*57:01:01 by three-nucleotide exchanges in exon 2.

Strong Anderson localization in cold atom quantum quenches.

Signatures of Anderson localization in the momentum distribution of a cold atom cloud after a quantum quench are studied. We consider a quasi-one-dimensional cloud initially prepared in a well-defined momentum state, and expanding for some time in a disorder speckle potential. Quantum interference generates a peak in the forward scattering amplitude which, unlike the common weak localization backscattering peak, is a signature of strong Anderson localization. We present a nonperturbative, and fully time resolved description of the phenomenon, covering the entire diffusion-to-localization crossover. Our results should be observable by present day experiments.

Randomized controlled trials of non-pharmacological interventions for healthy seniors: Effects on cognitive decline, brain plasticity and activities of daily living-A 23-year scoping review.

Little is known about the simultaneous effects of non-pharmacological interventions (NPI) on healthy older adults' behavior and brain plasticity, as measured by psychometric instruments and magnetic resonance imaging (MRI). The purpose of this scoping review was to compile an extensive list of randomized controlled trials published from January 1, 2000, to August 31, 2023, of NPI for mitigating and countervailing age-related physical and cognitive decline and associated cerebral degeneration in healthy elderly populations with a mean age of 55 and over. After inventorying the NPI that met our criteria, we divided them into six classes: single-domain cognitive, multi-domain cognitive, physical aerobic, physical non-aerobic, combined cognitive and physical aerobic, and combined cognitive and physical non-aerobic. The ultimate purpose of these NPI was to enhance individual autonomy and well-being by bolstering functional capacity that might transfer to activities of daily living. The insights from this study can be a starting point for new research and inform social, public health, and economic policies. The PRISMA extension for scoping reviews (PRISMA-ScR) checklist served as the framework for this scoping review, which includes 70 studies. Results indicate that medium- and long-term interventions combining non-aerobic physical exercise and multi-domain cognitive interventions best stimulate neuroplasticity and protect against age-related decline and that outcomes may transfer to activities of daily living.

Coherent forward scattering peak induced by Anderson localization.

Numerical simulations show that, at the onset of Anderson localization, the momentum distribution of a coherent wave packet launched inside a random potential exhibits, in the forward direction, a novel interference peak that complements the coherent backscattering peak. An explanation of this phenomenon in terms of maximally crossed diagrams predicts that the signal emerges around the localization time and grows on the scale of the Heisenberg time associated with the localization volume. Together, coherent back and forward scattering provide evidence for the occurrence of Anderson localization.

Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids.

Reports of spontaneous regressions of metastases and the demonstration of tumor-reactive cytotoxic T lymphocytes indicate the importance of the host's immune system in controlling the devastating course of metastatic renal cell carcinoma. Recent research indicates that immunization with hybrids of tumor and antigen presenting cells results in protective immunity and rejection of established tumors in various rodent models. Here, we present a hybrid cell vaccination study of 17 patients. Using electrofusion techniques, we generated hybrids of autologous tumor and allogeneic dendritic cells that presented antigens expressed by the tumor in concert with the co-stimulating capabilities of dendritic cells. After vaccination, and with a mean follow-up time of 13 months, four patients completely rejected all metastatic tumor lesions, one presented a 'mixed response', and two had a tumor mass reduction of greater 50%. We also demonstrate induction of HLA-A2-restricted cytotoxic T cells reactive with the Muc1 tumor-associated antigen and recruitment of CD8+ lymphocytes into tumor challenge sites. Our data indicate that hybrid cell vaccination is a safe and effective therapy for renal cell carcinoma and may provide a broadly applicable strategy for other malignancies with unknown antigens.

[Prerequisites for a new health care model for elderly people with multiple morbidities: results and conclusions from 3 years of research in the PRISCUS consortium]. / Voraussetzungen für ein neues Versorgungsmodell für ältere Menschen mit Multimorbidität: Ergebnisse und Schlussfolgerungen aus 3-jähriger Forschung im PRISCUS-Verbund.

BACKGROUND: The concurrent presence or manifestation of multiple chronic conditions, i.e. multimorbidity, poses a challenge to affected patients and their relatives, physicians, and practitioners, and to the health care system in general. Aiming to improve medical care for different chronic diseases, the Chronic Care Model also appears to be suited for multimorbidity. The established research consortium PRISCUS is trying to create some of the prerequisites for a new care model for multimorbid, elderly patients oriented along the lines of the Chronic Care Model. METHODS AND RESULTS: Four out of seven subprojects of the research consortium provide an overview of some of their findings. Topics in a sports medicine subproject were the assessment of physical activity by means of a newly developed questionnaire and the development and feasibility testing of an exercise program for elderly people with chronic conditions and mobility impairment. Partners from family medicine implemented geriatric assessment in a primary care setting and evaluated its consequences. In a pharmacological subproject, potentially inappropriate medication as well as drug-drug interactions and dosing errors were addressed. The health economic subproject investigated quality of life impairment due to multiple chronic diseases and the effects of multimorbidity on costs. CONCLUSIONS: The results of the PRISCUS research consortium allow a better description of consequences of multimorbidity and illustrate at least some new approaches towards prevention, diagnosis, and treatment of patients suffering from multimorbidity. Ongoing projects will test the efficacy of a physical activity program and a new complex intervention to reduce potentially inappropriate medication in the elderly. With this, the research consortium will create some prerequisites for a new health care model for patients with multimorbidity comparable to the Chronic Care Model.

Light quality and dormancy overcoming in seed germination of Echium plantagineum L. (Boraginaceae).

Light is considered a factor that influences the seed germination of many weed species, and it can signal whether the environmental conditions are favorable or are not favorable for germination. We aimed to study if there is an influence of light quality and dormancy overcoming in seed germination of Echium plantagineum L. We carried out a 2 x 6 factorial experiment, with and without dormancy overcoming with potassium nitrate followed by immersion in gibberellic acid; six light qualities, obtained through the light filters: blue, green, red, far-red, white light and absence of light. The evaluations performed were germination speed index (GSI), average germination time (AGT), germination at the four and 14 days after seeding (DAS), accumulated germination and relative frequency of germination. We observed significant interaction among the light qualities and seed dormancy overcoming or not for the studied variables. There was no significant effect of light qualities, in the evaluated variables, when performing dormancy overcoming, presenting germination above 90% in all the light qualities. However, without dormancy overcoming, we observed greater GSI, germination at four and 14 DAS for the red light filter with 5, 4, 29 and 45%, respectively. When the seeds were submitted to the absence of light, and without dormancy overcoming, there was only 7% of germination at 14 DAS. The seeds of E. plantagineum presented greater germination under incidence of red light, without dormancy overcoming, being classified as preferably positively photoblastics, provided that the dormancy is not overcome.

Self-peptide released from class II HLA-DR1 exhibits a hydrophobic two-residue contact motif.

Peptide fragments of foreign and self-proteins are of great immunologic importance as their binding to major histocompatibility complex (MHC) class I or II molecules makes an interaction with a corresponding T cell receptor possible. Recently, allele-specific peptide sequence motifs proved to be responsible for MHC binding, no matter whether self- or non-self-antigens were involved. Up to now, all investigated human class II-associated peptides were derived from foreign antigenic proteins. Therefore, we undertook sequence and binding analyses with a 16-mer self-peptide (SP3) that has been eluted from HLA-DR1. Here we demonstrate, by synthetic polyalanine-based 13-mer analogues of SP3, that two bulky hydrophobic anchor residues with relative spacing i, i + 8 are sufficient for high affinity binding. This is consistent with the hydrophobic i, i + 8 binding pattern recently found for DR-restricted T cell epitopes. Nevertheless, highly helical alanine-based design peptides with anchor spacing i, i + 9 exhibit maximal affinity, whereas replacement of alanine by helix destabilizing proline abrogates binding. Thus, a two-residue contact motif is the common minimal requirement of self- and foreign peptides for high affinity anchoring to HLA-DR1. In contrast to class I, the anchor spacing of DR1-associated peptides seems to bear some variability due to conformational diversity.

Efficacy and safety of levetiracetam for outpatient alcohol detoxification.

INTRODUCTION: Anticonvulsant drugs are increasingly being used for alcohol detoxification in in- and outpatient settings. The aim of this study was to examine the efficacy, medical safety and mid-term outcome of levetiracetam, a drug with no marked liver toxicity, for outpatient alcohol detoxification. METHODS: This was an open-label observational study. After screening eligibility for outpatient alcohol detoxification, patients were seen daily for 5 days and received levetiracetam in a flexible dosage regime between 500 and 4 000 mg/d for a maximum of 7 days. Diazepam was used as a rescue medication. The severity of alcohol withdrawal was evaluated daily using the ALCOHOL WITHDRAWAL SYNDROME SCALE (AWSS). Mid-term treatment outcome was assessed at a 6-month follow-up. RESULTS: A total number of 131 consecutively admitted alcohol-dependent patients received an outpatient detoxification treatment, 122 (93.1%) completed the programme successfully. The mean initial dose of levetiracetam was 1 850 mg/d. Alcohol withdrawal syndrome as indicated by the AWSS score decreased clearly over 5 days. Overall, the medication was well tolerated. There was no treatment discontinuations due to side effects of levetiracetam. No serious medical complications, especially seizures or deliria, were observed during the detoxification. At the 6-month follow-up, 57 patients (43.5%) were still abstinent. Patients with previous detoxifications had a significant higher risk for relapse (HR=1.88; p=0.016; CI 95%: 1.12-3.14) than patients without previous treatments. DISCUSSION: The findings of this study provide some evidence that levetiracetam is an efficacious and safe treatment option for outpatient alcohol detoxification. Further randomised, controlled trials including mid- and long-term follow-ups are needed to confirm these findings.

Tenascin is a cytoadhesive extracellular matrix component of the human hematopoietic microenvironment.

Tenascin is a large extracellular matrix (ECM) glycoprotein found in restricted tissue locations in the adult organism. It is copiously synthesized in regenerative organs or regenerating tissues and by certain tumors. We have analyzed the expression of tenascin in human long term bone marrow cultures as well as in cryostat sections of native bone marrow and found it strongly expressed by the stromal cells of the microenvironment. Two different protein subunits of 280 and 220 kD were detected by immunoblotting. These two forms are derived most likely from two different mRNA splice variants of 6 and 8 kb detected by Northern blotting. The in vivo analysis of cryostat sections showed a codistribution with other ECM molecules such as fibronectin and collagen type III in the microenvironment surrounding the maturing hematopoietic cells. Using two independent cell adhesion assays tenascin could be shown to function as a cytoadhesive molecule for hematopoietic cells. These data suggest a direct involvement of tenascin in the retention of hematopoietic progenitor cells in the stroma.

E-cadherin is functionally involved in the maturation of the erythroid lineage.

Differentiation and proliferation of hematopoietic progenitors take place in the bone marrow and is a tightly controlled process. Cell adhesion molecules of the integrin and immunoglobulin families have been shown to be involved in these processes, but almost nothing was known about the involvement of the cadherin family in the hematopoietic system. A PCR screening of RNA of human bone marrow mononuclear cells with specific primers for classical cadherins revealed that E-cadherin, which is mainly expressed by cells of epithelial origin, is also expressed by bone marrow cells. Western blot analysis and immunofluorescence staining of bone marrow sections confirmed this unexpected finding. A more detailed analysis using immunoaffinity columns and dual color flow cytometry showed that the expression of E-cadherin is restricted to defined maturation stages of the erythropoietic lineage. Erythroblasts and normoblasts express E-cadherin, mature erythrocytes do not. A functional role of E-cadherin in the differentiation process of the erythroid lineage was indicated by antibody-inhibition studies. The addition of anti-E-cadherin antibody to bone marrow mononuclear cultures containing exogeneous erythropoietin drastically diminished the formation of erythropoietic cells. These data suggest a non-anticipated expression and function of E-cadherin in one defined hematopoietic cell lineage.

Dexamethasone affects inflammation but not trypsinogen activation in experimental acute pancreatitis.

BACKGROUND/AIMS: Trypsinogen activation and inflammation are early events in acute pancreatitis. This experimental study aimed to show the effects of dexamethasone on them. METHODS: Cerulein and taurocholate pancreatitis were induced in 2 groups of 12 Wistar rats each. Six animals per group were injected with dexamethasone 1 h prior to the induction of acute pancreatitis. Amylase, phospholipase A2, TNF-alpha, IL-6, IL-10, alpha2-antiplasmin in plasma and trypsinogen activation peptide (TAP) in urine were measured in healthy rats, then 0.5 and 6 h after pancreatitis induction. A severity score based on edema, necrosis and ascites was calculated at 6 h. TNF-alpha, IL-6 and IL-10 were measured 0.5 h after laparotomy in a control sham-operated group of 6 rats. RESULTS: Inflammatory markers increased early in the course of both mild and severe acute pancreatitis and were significantly lowered by dexamethasone. The severity score was higher in taurocholate than in cerulein pancreatitis. It was significantly decreased by dexamethasone only in rats with mild pancreatitis. TAP remained unchanged in mild pancreatitis compared to healthy animals but increased late in the course of taurocholate pancreatitis. Trypsinogen activation was not affected by dexamethasone at all. CONCLUSION: Inflammation occurred earlier than the increase in urinary TAP in severe pancreatitis in rats. Dexamethasone inhibited inflammation but had no influence on TAP levels in experimental mild and severe acute pancreatitis.

Comparison of two different measurement techniques of hippocampal resection length in temporal lobe epilepsy: results of a prospective study.

BACKGROUND: Magnetic resonance imaging (MRI) volumetry has evolved to a highly sensitive method for presurgical detection of hippocampal sclerosis in temporal lobe epilepsy (TLE). Seizure resolution and neuropsychological sequelae are believed to correlate with extent of resection. Therefore an easy volumetric method to determine extent of resection is desirable. The purpose of this work is to evaluate and compare two different measurement techniques for hippocampal resection length. METHODS: Sixty-one patients with a mean seizure history of 25.1 years and medically intractable TLE were included. They underwent MRI with sagittal acquired 3D T1-weighted spoiled gradient recalled echo sequence in 1 mm(3) isotropic voxel. Hippocampal resection length was calculated with two different methods. In the slice counting method (SCM) the number of consecutive 1-mm-thick slices containing resected hippocampus formation was counted. In the vector method (VM) the sum of the oblique and thus longer distances between the centre points of segmented hippocampal areas on each MRI slice were calculated. RESULTS: Since the hippocampus is a curved body, the resection lengths measured with VM were always larger than measured with SCM. The comparison of resection length expressed in "percent of total length" showed good agreement between the two methods, because unlike the absolute values of resection length, the percentage values are unaffected by the three-dimensional shape of the hippocampus. CONCLUSION: The easier and quicker method of "slice counting" may be used to determine resection length expressed in "percent of total length", giving reliable values for resection length but causing less volumetric work.

Double sigmoid colon perforation by a migrated biliary stent.

The case of a female patient with a covered double perforation of the sigmoid colon is described. The perforation was due to a migrated plastic biliary stent inserted 3 weeks earlier for benign biliary obstruction and was facilitated by the presence of expressed diverticulosis of the colon. The lack of peritonitis and the early surgical procedure allowed a successful primary reconstruction after the colonic resection. Since the use of biliary stents is constantly increasing, such complications as stent migration and perforation should always be kept in mind by surgeons.