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Abstract Purpose Combined immunomodulatory and antiviral treatment was administered to three patients with newly diagnosed HIV-associated primary central nervous system lymphoma (PCNSL) in an attempt to improve outcomes. Patients and methods Three patients from our institution who were recently diagnosed with HIV-associated PCNSL received intravenous azidothymidine (AZT) 1.6 gr. bid for two weeks, followed by oral AZT 250 mg bid from day 15. In addition, complementary highly active antiretroviral therapy (HAART) with a second nucleoside reverse transcriptase inhibitor (NRTI) plus one protease inhibitor (PI) and interleukin 2 (IL-2) subcutaneously 2 million units twice daily (bid) plus foscarnet 90 mg/kg bid were administered on days 1-14. One patient received anti-EpsteinBarr virus (EBV)-maintenance therapy with ganciclovir, followed by cidofovir 1. Results All patients experienced progressive disease while on induction therapy, and switched early to whole-brain radiation therapy (WBRT) as second linetreatment. No grade 3 or 4 toxicities were observed. Two patients died on days 50 and 166 respectively due to progressive disease. The third patient with histologically proven lymphoproliferation and only suspected PCNSL remained alive at 53 months. He was on HAART and remained clinically and neurologically stable. Conclusion Although IL-2, HAART, high-dose AZT and foscarnet are used for other HIV-related conditions, they did not demonstrate benefit in lymphoma remission for 2 HIVassociated PCNSL patients. The third patient went into delayed remission after additional radiotherapy and was in good clinical and neurological health status over 53 months after diagnosis.

Examines the transfer of the fungicide vinclozolin from treated to untreated plants via volatilization. Lactuca sativa; Spinacia oleracea; Lolium multiflorum.

Ultraviolet (UV) irradiation of the skin causes mutations that can promote the development of melanoma and nonmelanoma skin cancer. High-dose UVB exposure triggers a vigorous skin reaction characterized by inflammation resulting in acute sunburn. This response includes the formation of sunburn cells and keratinocytes (KC) undergoing programmed cell death (apoptosis) when repair mechanisms of DNA damage are inadequate. The primary objective of this research was to clarify the involvement of Langerhans cells (LC) in the development of acute sunburn following intense UVB skin irradiation. To address this, we subjected the dorsal skin of mice to a single high-dose UVB exposure and analyzed the immediate immune response occurring within the skin tissue. Acute sunburn triggered an activation of LC, coinciding with a rapid influx of neutrophils that produced TNF-α. Furthermore, our investigation unveiled a marked increase in DNA-damaged KC and the subsequent induction of apoptosis in these cells. Importantly, we demonstrate a crucial link between the inflammatory cascade, the initiation of apoptosis in DNA-damaged KC, and the presence of LC in the skin. LC were observed to modulate the chemokine response in the skin following exposure to UVB, thereby affecting the trafficking of neutrophils. Skin lacking LC revealed diminished inflammation, contained fewer TNF-α-producing neutrophils, and due to the prevention of apoptosis induction, a lingering population of DNA-damaged KC, presumably carrying the risk of enduring genomic alterations. In summary, our results underscore the pivotal role of LC in preserving the homeostasis of UVB-irradiated skin. These findings contribute to a deeper understanding of the intricate mechanisms underlying acute sunburn responses and their implications for UV-induced skin cancer., (© 2024 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.)

Background: Tumor-targeted therapy causes impressive tumor regression, but the emergence of resistance limits long-term survival benefits in patients. Little information is available on the role of the myeloid cell network, especially dendritic cells (DC) during tumor-targeted therapy., Methods: Here, we investigated therapy-mediated immunological alterations in the tumor microenvironment (TME) and tumor-draining lymph nodes (LN) in the D4M.3A preclinical melanoma mouse model (harboring the V-Raf murine sarcoma viral oncogene homolog B (BRAF) V600E mutation) by using high-dimensional multicolor flow cytometry in combination with multiplex immunohistochemistry. This was complemented with RNA sequencing and cytokine quantification to characterize the immune status of the tumors. The importance of T cells during tumor-targeted therapy was investigated by depleting CD4 + or CD8 + T cells in tumor-bearing mice. Tumor antigen-specific T-cell responses were characterized by performing in vivo T-cell proliferation assays and the contribution of conventional type 1 DC (cDC1) to T-cell immunity during tumor-targeted therapy was assessed using Batf3 -/- mice lacking cDC1., Results: Our findings reveal that BRAF-inhibitor therapy increased tumor immunogenicity, reflected by an upregulation of genes associated with immune activation. The T cell-inflamed TME contained higher numbers of activated cDC1 and cDC2 but also inflammatory CCR2-expressing monocytes. At the same time, tumor-targeted therapy enhanced the frequency of migratory, activated DC subsets in tumor-draining LN. Even more, we identified a cDC2 population expressing the Fc gamma receptor I (FcγRI)/CD64 in tumors and LN that displayed high levels of CD40 and CCR7 indicating involvement in T cell-mediated tumor immunity. The importance of cDC2 is underlined by just a partial loss of therapy response in a cDC1-deficient mouse model. Both CD4 + and CD8 + T cells were essential for therapy response as their respective depletion impaired therapy success. On resistance development, the tumors reverted to an immunologically inert state with a loss of DC and inflammatory monocytes together with the accumulation of regulatory T cells. Moreover, tumor antigen-specific CD8 + T cells were compromised in proliferation and interferon-γ-production., Conclusion: Our results give novel insights into the remodeling of the myeloid landscape by tumor-targeted therapy. We demonstrate that the transient immunogenic tumor milieu contains more activated DC. This knowledge has important implications for the development of future combinatorial therapies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

This article is part of the Dendritic Cell Guidelines article series, which provides a collection of state-of-the-art protocols for the preparation, phenotype analysis by flow cytometry, generation, fluorescence microscopy and functional characterization of mouse and human dendritic cells (DC) from lymphoid organs and various nonlymphoid tissues. DC are sentinels of the immune system present in almost every mammalian organ. Since they represent a rare cell population, DC need to be extracted from organs with protocols that are specifically developed for each tissue. This article provides detailed protocols for the preparation of single-cell suspensions from various mouse nonlymphoid tissues, including skin, intestine, lung, kidney, mammary glands, oral mucosa and transplantable tumors. Furthermore, our guidelines include comprehensive protocols for multiplex flow cytometry analysis of DC subsets and feature top tricks for their proper discrimination from other myeloid cells. With this collection, we provide guidelines for in-depth analysis of DC subsets that will advance our understanding of their respective roles in healthy and diseased tissues. While all protocols were written by experienced scientists who routinely use them in their work, this article was also peer-reviewed by leading experts and approved by all coauthors, making it an essential resource for basic and clinical DC immunologists., (© 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)

Obesity is a complex disease highly related to diet and lifestyle and is associated with low amount of thermogenic adipocytes. Therapeutics that regulate brown adipocyte recruitment and activity represent interesting strategies to fight overweight and associated comorbidities. Recent studies suggest a role for several fatty acids and their metabolites, called lipokines, in the control of thermogenesis. The purpose of this work was to analyze the role of several lipokines in the control of brown/brite adipocyte formation. We used a validated human adipocyte model, human multipotent adipose-derived stem cell model (hMADS). In the absence of rosiglitazone, hMADS cells differentiate into white adipocytes, but convert into brite adipocytes upon rosiglitazone or prostacyclin 2 (PGI2) treatment. Gene expression was quantified using RT-qPCR and protein levels were assessed by Western blotting. We show here that lipokines such as 12,13-diHOME, 12-HEPE, 15dPGJ2 and 15dPGJ3 were not able to induce browning of white hMADS adipocytes. However, both fatty acid esters of hydroxy fatty acids (FAHFAs), 9-PAHPA and 9-PAHSA potentiated brown key marker UCP1 mRNA levels. Interestingly, CTA2, the stable analog of thromboxane A2 (TXA2), but not its inactive metabolite TXB2, inhibited the rosiglitazone and PGI2-induced browning of hMADS adipocytes. These results pinpoint TXA2 as a lipokine inhibiting brown adipocyte formation that is antagonized by PGI2. Our data open new horizons in the development of potential therapies based on the control of thromboxane A2/prostacyclin balance to combat obesity and associated metabolic disorders.

Objective: Classical ATP-independent non-shivering thermogenesis enabled by uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) is activated, but not essential for survival, in the cold. It has long been suspected that futile ATP-consuming substrate cycles also contribute to thermogenesis and can partially compensate for the genetic ablation of UCP1 in mouse models. Futile ATP-dependent thermogenesis could thereby enable survival in the cold even when brown fat is less abundant or missing., Methods: In this study, we explore different potential sources of UCP1-independent thermogenesis and identify a futile ATP-consuming triglyceride/fatty acid cycle as the main contributor to cellular heat production in brown adipocytes lacking UCP1. We uncover the mechanism on a molecular level and pinpoint the key enzymes involved using pharmacological and genetic interference., Results: ATGL is the most important lipase in terms of releasing fatty acids from lipid droplets, while DGAT1 accounts for the majority of fatty acid re-esterification in UCP1-ablated brown adipocytes. Furthermore, we demonstrate that chronic cold exposure causes a pronounced remodeling of adipose tissues and leads to the recruitment of lipid cycling capacity specifically in BAT of UCP1-knockout mice, possibly fueled by fatty acids from white fat. Quantification of triglyceride/fatty acid cycling clearly shows that UCP1-ablated animals significantly increase turnover rates at room temperature and below., Conclusion: Our results suggest an important role for futile lipid cycling in adaptive thermogenesis and total energy expenditure., (Copyright © 2022 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Activation of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) upon cold stimulation leads to substantial increase in energy expenditure to defend body temperature. Increases in energy expenditure after a high-caloric food intake, termed diet-induced thermogenesis, are also attributed to BAT. These properties render BAT a potential target to combat diet-induced obesity. However, studies investigating the role of UCP1 to protect against diet-induced obesity are controversial and rely on the phenotyping of a single constitutive UCP1-knockout model. To address this issue, we generated a novel UCP1-knockout model by Cre-mediated deletion of exon 2 in the UCP1 gene. We studied the effect of constitutive UCP1 knockout on metabolism and the development of diet-induced obesity. UCP1 knockout and wild-type mice were housed at 30°C and fed a control diet for 4 wk followed by 8 wk of high-fat diet. Body weight and food intake were monitored continuously over the course of the study, and indirect calorimetry was used to determine energy expenditure during both feeding periods. Based on Western blot analysis, thermal imaging and noradrenaline test, we confirmed the lack of functional UCP1 in knockout mice. However, body weight gain, food intake, and energy expenditure were not affected by loss of UCP1 function during both feeding periods. We introduce a novel UCP1-KO mouse enabling the generation of conditional UCP1-knockout mice to scrutinize the contribution of UCP1 to energy metabolism in different cell types or life stages. Our results demonstrate that UCP1 does not protect against diet-induced obesity at thermoneutrality. NEW & NOTEWORTHY We provide evidence that the abundance of UCP1 does not influence energy metabolism at thermoneutrality studying a novel Cre-mediated UCP1-KO mouse model. This model will be a foundation for a better understanding of the contribution of UCP1 in different cell types or life stages to energy metabolism.

Extrahepatic tissues which oxidise ketone bodies also have the capacity to accumulate them under particular conditions. We hypothesised that acetyl-coenzyme A (acetyl-CoA) accumulation and altered redox status during low-flow ischaemia would support ketone body production in the heart. Combining a Langendorff heart model of low-flow ischaemia/reperfusion with liquid chromatography coupled tandem mass spectrometry (LC-MS/MS), we show that β-hydroxybutyrate (β-OHB) accumulated in the ischaemic heart to 23.9 nmol/gww and was secreted into the coronary effluent. Sodium oxamate, a lactate dehydrogenase (LDH) inhibitor, increased ischaemic β-OHB levels 5.3-fold and slowed contractile recovery. Inhibition of β-hydroxy-β-methylglutaryl (HMG)-CoA synthase (HMGCS2) with hymeglusin lowered ischaemic β-OHB accumulation by 40%, despite increased flux through succinyl-CoA-3-oxaloacid CoA transferase (SCOT), resulting in greater contractile recovery. Hymeglusin also protected cardiac mitochondrial respiratory capacity during ischaemia/reperfusion. In conclusion, net ketone generation occurs in the heart under conditions of low-flow ischaemia. The process is driven by flux through both HMGCS2 and SCOT, and impacts on cardiac functional recovery from ischaemia/reperfusion., Competing Interests: RL Ross T. Lindsay is affiliated with BioPharmaceuticals R&D, AstraZeneca Ltd. The author has no financial interests to declare. SD, DK, DM, JW, CC, JG, AM No competing interests declared, (© 2021, Lindsay et al.)

Scope: Brown and brite adipocytes within the mammalian adipose organ provide non-shivering thermogenesis and thus, have an exceptional capacity to dissipate chemical energy as heat. Polyunsaturated fatty acids (PUFA) of the n3-series, abundant in fish oil, have been repeatedly demonstrated to enhance the recruitment of thermogenic capacity in these cells, consequently affecting body adiposity and glucose tolerance. These effects are scrutinized in mice housed in a thermoneutral environment and in a human dietary intervention trial., Methods and Results: Mice are housed in a thermoneutral environment eliminating the superimposing effect of mild cold-exposure on thermogenic adipocyte recruitment. Dietary fish oil supplementation in two different inbred mouse strains neither affects body mass trajectory nor enhances the recruitment of brown and brite adipocytes, both in the presence and absence of a β3-adrenoreceptor agonist imitating the effect of cold-exposure on adipocytes. In line with these findings, dietary fish oil supplementation of persons with overweight or obesity fails to recruit thermogenic adipocytes in subcutaneous adipose tissue., Conclusion: Thus, the authors' data question the hypothesized potential of n3-PUFA as modulators of adipocyte-based thermogenesis and energy balance regulation., (© 2020 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.)

Metabolites of omega-6 and omega-3 polyunsaturated fatty acids are important signaling molecules implicated in the control of adipogenesis and energy balance regulation. Some of these metabolites belonging to the group of oxylipins have been associated with non-shivering thermogenesis in mice mediated by brown or brite adipose tissue. We aimed to identify novel molecules with thermogenic potential and to clarify the relevance of these findings in a translational context. Therefore, we characterized and compared the oxylipin profiles of murine and human adipose tissues with different abundance of brown or brite adipocytes. A broad panel of 36 fatty acid metabolites was quantified in brown and white adipose tissues of C57BL/6J mice acclimatized to different ambient temperatures and in biopsies of human supraclavicular brown and white adipose tissue. The oxylipin profile of murine brite adipose tissue was not distinguishable from white adipose tissue, suggesting that adipose tissue browning in vivo is not associated with major changes in the oxylipin metabolism. Human brown and white adipose tissue also exhibited similar metabolite profiles. This is in line with previous studies proposing human brown adipose tissue to resemble the nature of murine brite adipose tissue representing a heterogeneous mixture of brite and white adipocytes. Although the global oxylipin profile served as a marker for the abundance of thermogenic adipocytes in bona fide brown but not white adipose tissue, we identified 5-HETE and 5,6-EET as individual compounds consistently associated with the abundance of brown or brite adipocytes in human BAT and murine brite fat. Further studies need to establish whether these candidates are mere markers or functional effectors of thermogenic capacity., (Copyright © 2020 Dieckmann, Maurer, Fromme, Colson, Virtanen, Amri and Klingenspor.)

Fatty acids are essential contributors to adipocyte-based non-shivering thermogenesis by acting as activators of uncoupling protein 1 and serving as fuel for mitochondrial heat production. Novel evidence suggests a contribution to this thermogenic mechanism by their conversion to bioactive compounds. Mammalian cells produce a plethora of oxylipins and endocannabinoids, some of which have been identified to affect the abundance or thermogenic activity of brown and brite adipocytes. These effectors are produced locally or at distant sites and signal toward thermogenic adipocytes via a direct interaction with these cells or indirectly via secondary mechanisms. These interactions are evoked by the activation of receptor-mediated pathways. The endogenous production of these compounds is prone to modulation by the dietary intake of the respective precursor fatty acids. The effect of nutritional interventions on uncoupling protein 1-derived thermogenesis may thus at least in part be conferred by the production of a supportive oxylipin and endocannabinoid profile. The manipulation of this system in future studies will help to elucidate the physiological potential of these compounds as novel, endogenous regulators of non-shivering thermogenesis.

Background: Conventional rabies pre-exposure prophylaxis (PrEP) and Japanese encephalitis (JE) primary series vaccination regimens each require up to 4 weeks to complete and, thus, may not be feasible for individuals who need these immunizations on short notice. This Phase 3b, randomized, controlled, observer-blind study evaluated the immunogenicity and safety of concomitant administration of a purified chick embryo cell culture rabies vaccine and an inactivated, adsorbed JE vaccine according to an accelerated (1 week) regimen when compared with the conventional regimens (4 weeks). This report describes the kinetics of immune responses up to 1 year after vaccination., Methods: A total of 661 healthy adults (18 to ≤65 years) were randomized into the following accelerated or conventional vaccine regimens: Rabies + JE-Conventional, Rabies + JE-Accelerated, Rabies-Conventional and JE-Conventional. Immunogenicity was assessed by virus neutralization tests. Safety and tolerability were also evaluated., Results: Irrespective of rabies vaccination regimen, ≥97% of subjects had adequate levels of rabies virus neutralizing antibody (RVNA) concentrations (≥0.5 IU/ml) up to Day 57, with percentages of subjects with RVNA concentrations ≥0.5 IU/ml at Day 366 ranging between 68% in the Rabies + JE-Accelerated group and 80% of subjects in the Rabies-Conventional group. The Rabies + JE-Accelerated group revealed high JE neutralizing antibody titers at all-time points. At Day 366, the percentage of subjects with antibody titers indicative of seroprotection (PRNT50 titers ≥1:10) remained high across JE vaccine groups (86-94%)., Conclusions: The accelerated PrEP rabies and JE vaccination regimens, once licensed, could represent a valid alternative in the short-term to currently recommended conventional regimens. The concomitant administration of these two vaccines does not compromise immune responses to any of the vaccine antigens particularly when aiming for short-term protection. Further evidence will clarify the need for and timing to administration of rabies vaccine booster doses in subjects primed with an accelerated PrEP regimen. (NCT01662440)., (© International Society of Travel Medicine, 2016. All rights reserved. Published by Oxford University Press. For permissions, please e-mail: journals.permissions@oup.com.)

Background: International travel contributes to the spread of multidrug-resistant microorganisms including extended spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). We assessed the proportion of faecal carriers of ESBL-PE among 211 patients with gastrointestinal symptoms who returned to Berlin, Germany, after international travel., Methods: ESBL-PE were screened for on chromogenic agar, antimicrobial susceptibility testing was performed, and ESBL-genes were genotyped. Travel-related data were assessed by questionnaire., Results: Diarrhoea, abdominal pain and nausea were the main symptoms. Half of the travellers carried ESBL-PE (97% Escherichia coli); the proportion was highest for returnees from India (72%) and mainland Southeast Asia (59%), and comparatively lower for Africa (33%) and Central America (20%). Co-resistance to fluoroquinolones (particularly in isolates from India), gentamicin and cotrimoxazole was frequent but all isolates were carbapenem-susceptible. ESBL-PE carriage decreased with increasing timespan from return to presentation, and with age. At revisit of initially ESBL-PE positive patients half a year later, 28% (17/61) of the individuals were still carriers, CTX-M groups being congruent with the initial isolates. CTX-M groups 9 and 1/9, vegetarian diet and cat ownership tended to be associated with ESBL-PE carriage upon revisit., Conclusions: Travellers, particularly those returning from India and Southeast Asia, constitute a relevant source of potential spread of ESBL-PE. Carriage declines over time but ESBL-PE persist for at least 6 months in a substantial proportion of individuals. Both genetic characteristics of the bacteria and lifestyle factors seem to contribute to persistent carriage of ESBL-PE. A recent, extra-European travel history argues for ESBL-PE screening and contact precautions for patients admitted to hospital., (© International Society of Travel Medicine, 2016. All rights reserved. Published by Oxford University Press. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The current Japanese encephalitis (JE) vaccination regimen requires two doses and 4 weeks to complete, which may not always be feasible for travelers on short notice. One of the primary endpoints of this phase III study was to demonstrate noninferiority of immune responses to a JE vaccine following an accelerated 1-week JE vaccination regimen administered concomitantly with a rabies vaccine as compared to a standard 4-week JE regimen alone. In addition, the immunogenicity of concomitant administration of JE and rabies vaccines following standard regimens was evaluated, as well as the tolerability and safety profile of each regimen under study., Methods: Healthy adults aged 18 to ≤65 years were randomized to regimens with an accelerated or standard schedule: JE+rabies-standard (n = 167), JE+rabies-accelerated (n = 217) or JE-standard (n = 56). Immunogenicity against JE antigen was assessed by a 50% plaque reduction neutralization test (PRNT50 ) titer of ≥1 : 10, measured 28 days after last active vaccine (LAV) administration. Solicited reactions were collected 7 days after each vaccination; spontaneously reported adverse events (AEs) and serious AEs were monitored up to day 57. This paper reports results until day 57., Results: Noninferiority of immune responses was established for JE+rabies-accelerated compared to the JE-standard regimen 28 days after LAV administration. Overall, 99% and 100% of subjects in the JE+rabies-accelerated and JE-standard groups, respectively, achieved PRNT50 titers of ≥1 : 10 at 28 days after LAV administration. No impact of concomitant rabies vaccination was observed either on immune responses or on the safety profile of the JE vaccine., Conclusions: This was the first randomized, controlled trial that demonstrated the strong short-term immunogenicity of a new, accelerated, 1-week JE-regimen, which was noninferior to that of the standard regimen, with a satisfactory tolerability and safety profile and no impact of concomitant rabies vaccination. This accelerated regimen, if licensed, could potentially be a valid alternative for individuals requiring a primary series of JE vaccination and rabies pre-exposure prophylaxis on short notice., (© 2015 International Society of Travel Medicine.)

Background: For individuals traveling at short notice to rabies and Japanese encephalitis (JE) endemic countries, concomitant administration of travel vaccines within a short period is often required., Methods: The aim of this study was to determine whether an accelerated (one-week: Days 1-8) pre-exposure rabies (Rabipur(®), Novartis Vaccines) vaccination regimen administered concomitantly with a Japanese encephalitis (JE) vaccination (Ixiaro(®), Valneva) regimen, is non-inferior to the standard (four-week: Days 1, 8, 29) rabies regimen administered alone or concomitantly with the JE vaccine. Healthy adults (18 to ≤ 65 years) were randomized into Rabies + JE-Standard, Rabies + JE-Accelerated, Rabies-Standard and JE-Standard groups. Relative immunogenicity for rabies in each regimen was assessed using the rapid fluorescent focus inhibition test. Safety was evaluated up to and including Day 57., Results: Non-inferior immunogenicity for rabies was established between the Rabies + JE-Accelerated group compared to both the Rabies-Standard and Rabies + JE-Standard groups; as well as between the Rabies + JE-Standard regimen and the Rabies-Standard regimen. By Day 57, adequate neutralizing levels were achieved by 97-100% of subjects across all groups. Adverse events (AEs) were comparable for all groups., Conclusions: An accelerated pre-exposure rabies and JE vaccination regimen is non-inferior to the standard four-week rabies regimen and may thus provide a more convenient regimen for individuals traveling to endemic countries at short notice. NCT01662440., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Neurocysticercosis (NCC), the central nervous system infection by Taenia solium larvae, is a preventable and treatable cause of epilepsy. In Sub-Saharan Africa, the role of NCC in epilepsy differs geographically and, overall, is poorly defined. We aimed at contributing specific, first data for Rwanda, assessing factors associated with NCC, and evaluating a real-time PCR assay to diagnose NCC in cerebrospinal fluid (CSF)., Methodology/principal Findings: At three healthcare facilities in southern Rwanda, 215 people with epilepsy (PWE) and 51 controls were clinically examined, interviewed, and tested by immunoblot for cysticerci-specific serum antibodies. Additionally, CSF samples from PWE were tested for anticysticercal antibodies by ELISA and for parasite DNA by PCR. Cranial computer tomography (CT) scans were available for 12.1% of PWE with additional symptoms suggestive of NCC. The Del Brutto criteria were applied for NCC diagnosis. Cysticerci-specific serum antibodies were found in 21.8% of PWE and 4% of controls (odds ratio (OR), 6.69; 95% confidence interval (95%CI), 1.6-58.7). Seropositivity was associated with age and lack of safe drinking water. Fifty (23.3%) PWE were considered NCC cases (definitive, based on CT scans, 7.4%; probable, mainly based on positive immunoblots, 15.8%). In CSF samples from NCC cases, anticysticercal antibodies were detected in 10% (definitive cases, 25%) and parasite DNA in 16% (definitive cases, 44%). Immunoblot-positive PWE were older (medians, 30 vs. 22 years), more frequently had late-onset epilepsy (at age >25 years; 43.5% vs. 8.5%; OR, 8.30; 95%CI, 3.5-20.0), and suffered from significantly fewer episodes of seizures in the preceding six months than immunoblot-negative PWE., Conclusions/significance: NCC is present and contributes to epilepsy in southern Rwanda. Systematic investigations into porcine and human cysticercosis as well as health education and hygiene measures for T. solium control are needed. PCR might provide an additional, highly specific tool in NCC diagnosis.

Background: Schistosomiasis is common in many African regions and poses a risk for travelers and the local population. So far, schistosomiasis in travelers or expatriates returning from the Tanzanian bank of Lake Tanganyika has not been reported., Methods: We report a group of students who sought treatment with signs of acute schistosomiasis after having returned from Lake Tanganyika, Tanzania. Information as to travel and exposure as well as clinical and laboratory data were collected., Results: Schistosomiasis was diagnosed in 8 of 16 students from Berlin, Germany, who had returned from a 2- to 3-month stay of fieldwork in Kigoma District at Lake Tanganyika, Tanzania. All 16 students reported frequent freshwater exposure at the lake. Six patients showed signs of acute schistosomiasis and had fever, and some of them also had cough, weakness, headache, or abdominal pain. Eosinophilia was present in five of the six symptomatic individuals. Notably, two serologically enzyme-linked immunosorbent assay (ELISA)-positive individuals did not report or present with symptoms or abnormal laboratory parameters. Schistosoma mansoni eggs were found in one symptomatic and one asymptomatic individual each. Blood and stool samples from the other eight individuals who were equally exposed to freshwater yielded negative results., Conclusions: This is the first report of an outbreak of acute schistosomiasis imported from the Tanzanian shore of Lake Tanganyika and highlights the risk for travelers and the local population of acquiring the infection in that part of Tanzania. It provides arguments for routine serological screening for schistosomiasis in individuals who had prior freshwater contact in endemic areas, irrespective of symptoms or other laboratory findings., (© 2013 International Society of Travel Medicine.)

Shedding light on the matter: Rhenium(I) indolato complexes with highly potent visible-light-triggered antiproliferative activity (complex 1: EC50 light=0.1 μM vs EC50 dark=100 μM) in 2D- and 3D-organized cancer cells are reported and can be traced back to an efficient generation of singlet oxygen, causing rapid morphological changes and an induction of apoptosis., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Acute schistosomiasis constitutes a rare but serious condition in individuals experiencing their first prepatent Schistosoma infection. To circumvent costly and time-consuming diagnostics, an early and rapid diagnosis is required. So far, classic diagnostic tools such as parasite microscopy or serology lack considerable sensitivity at this early stage of Schistosoma infection. To validate the use of a blood based real-time polymerase chain reaction (PCR) test for the detection of Schistosoma DNA in patients with acute schistosomiasis who acquired their infection in various endemic regions we conducted a European-wide prospective study in 11 centres specialized in travel medicine and tropical medicine., Methods: Patients with a history of recent travelling to schistosomiasis endemic regions and freshwater contacts, an episode of fever (body temperature ≥38.5°C) and an absolute or relative eosinophil count of ≥700/μl or 10%, were eligible for participation. PCR testing with DNA extracted from serum was compared with results from serology and microscopy., Results: Of the 38 patients with acute schistosomiasis included into the study, PCR detected Schistosoma DNA in 35 patients at initial presentation (sensitivity 92%). In contrast, sensitivity of serology (enzyme immunoassay and/or immunofluorescence assay) or parasite microscopy was only 70% and 24%, respectively., Conclusion: For the early diagnosis of acute schistosomiasis, real-time PCR for the detection of schistosoma DNA in serum is more sensitive than classic diagnostic tools such as serology or microscopy, irrespective of the region of infection. Generalization of the results to all Schistosoma species may be difficult as in the study presented here only eggs of S. mansoni were detected by microscopy. A minimum amount of two millilitre of serum is required for sufficient diagnostic accuracy.

The chemical profiling of illicit drugs is an important analytical tool to support the work of investigating and law enforcement authorities. In our work, comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOFMS) combined with nontargeted, pixel-based data analysis was adapted for the chemical profiling of 3,4-methylenedioxymethamphetamine (MDMA). The validity and benefit of this approach was evaluated by analyzing a well-investigated set of MDMA samples. Samples were prepared according to a harmonized extraction protocol to ensure the comparability of the chemical signatures. The nontargeted approach comprises preprocessing followed by analysis of variances as a fast filter algorithm for selection of a variable subset followed by partial least squares discriminant analysis for reduction to promising marker compounds for discrimination of the samples according to their chemical profile. Forty-seven potential marker compounds were determined, covering most of the target impurities known from the harmonized one-dimensional profiling as well as other compounds not previously elucidated., (© 2012 American Academy of Forensic Sciences.)

We report a case of falciparum malaria in a traveler 9 days after successful treatment of ovale malaria. The underlying, cryptic mixed-species infection was primarily undetectable with standard laboratory diagnostics. This case highlights the limitations of these tests and the unpredictability of typical incubation periods in the individual case., (© 2012 International Society of Travel Medicine.)

The main objectives of the European project "Collaborative Harmonization of Methods for Profiling of Amphetamine Type Stimulants" (CHAMP) funded by the sixth framework programme of the European Commission, included the harmonization of MDMA profiling methods and the creation of a common database in a drug intelligence perspective. In the preliminary stages of this project, the participating laboratories analysed the physical characteristics, the chemical composition and the organic impurities of MDMA tablets, using the previously harmonized methods. The aim of the present work was to apply statistical treatments to the recorded data in order to evaluate their potential in the fight against drug trafficking. Comparable working procedures were applied on the different types of data. The first part of this article deals with organic impurities data, while the second part focuses on the potential of the physical characteristics. Organic impurities data were recorded by a harmonized Gas Chromatography/Mass Spectrometry (GC/MS) method previously developed. Statistical analysis provided a selection of pertinent variables among the 46 organic impurities identified in the chromatograms. Correlation coefficients were used to yield separation between populations of samples coming from the same synthesis batch and samples coming from different batches. It was shown that correlation measurements based on Pearson and cosine functions applied to the data pre-treated by normalisation to the sum of peak responses followed by the square root provided an excellent discrimination between the two populations. The statistical methods applied to organic impurities profiles proved to be excellent techniques to differentiate samples from different batches and to highlight operational links between samples.

Catatonic schizophrenia can be distinguished from paranoid schizophrenia by prominent behavioral and motor anomalies. As demonstrated in recent imaging studies, behavioral symptoms may be related to dysfunction in the ventral prefrontal cortex. However, the neuropsychological correlates of ventral prefrontal cortical dysfunction remain unclear. In an exploratory study, we investigated eight patients with catatonic schizophrenia and compared them with 19 patients with paranoid schizophrenia and 26 healthy subjects. The Iowa Gambling Task (IGT) and the Object Alternation Task (OAT) served as measures of ventral prefrontal cortical function. In addition, other prefrontal cortical tests such as a visual working memory task, a Go-NoGo task, and the Wisconsin Card Sorting Test, as well as attentional tasks, were included in the test battery. Catatonic patients showed significant deficits in the IGT characterized by an inability to shift from the initial preference for high-risk cards to a more advantageous strategy with low-risk cards. Moreover, catatonic patients showed significant deficits in the OAT. In conclusion, our preliminary results suggest a specific deficit in catatonic schizophrenia in those neuropsychological measures that are associated with ventral prefrontal cortical function.

Objective: The aim of the study was to validate a French adaptation of the 5th version of the Addiction Severity Index (ASI) instrument in a Swiss sample of illicit drug users., Participants and Setting: The participants in the study were 54 French-speaking dependent patients, most of them with opiates as the drug of first choice., Procedure: Analyses of internal consistency (convergent and discriminant validity) and reliability, including measures of test-retest and inter-observer correlations, were conducted., Results: Besides good applicability of the test, the results on composite scores (CSs) indicate comparable results to those obtained in a sample of American opiate-dependent patients. Across the seven dimensions of the ASI, Cronbach's alpha ranged from 0.42 to 0.76, test-retest correlations coefficients ranged from 0.48 to 0.98, while for CSs, inter-observer correlations ranged from 0.76 to 0.99., Conclusions: Despite several limitations, the French version of the ASI presents acceptable criteria of applicability, validity and reliability in a sample of drug-dependent patients., (Copyright 2004 S. Karger AG, Basel)