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Background Severe hepatosplenic complications arise in patients with chronic Schistosoma mansoni infection after heavy exposure to disease agents in endemic areas. These complications are rarely reported and, hence, underestimated. Case presentation We report on eight patients with severe morbidity associated with S. mansoni infection in Ituri Province, northeastern Democratic Republic of Congo (DRC). The patients were identified during a community-based survey in 2017; one patient was seen at the district hospital. After taking the patients’ history, a clinical examination and an abdominal ultrasonographical examination were performed. S. mansoni infection was diagnosed in fecal (Kato-Katz technique) and urine (point-of-case circulating cathodic antigen test) samples. These eight patients with severe intestinal and hepatosplenic complications were identified from four villages with high S. mansoni infection prevalence and related morbidity. The patients’ ages ranged from 19 to 57 years; four patients were women. Three patients reported hematemesis. Two patients were severely anemic. All patients reported non-specific abdominal symptoms, such as diarrhea (six patients), abdominal pain (seven patients), and blood in the stool (five patients), as well as weight loss (two patients). Abdominal ultrasonography revealed ascites in four patients. All patients had portal hypertension with hepatomegaly (seven patients) or splenomegaly (five patients). Of the six patients with a discernable liver parenchyma pattern, five displayed pattern F and three patient displayed pattern E. Liver parenchyma was not visible for two patients with severe ascites. An S. mansoni infection was confirmed in six patients, with infection intensity ranging from light to heavy. All S. mansoni positive patients were treated with praziquantel (40 mg/kg body weight) and referred to the district hospital for follow-up. One patient with severe ascites died two weeks after we saw her. Due to security and accessibility reasons, the villages could not be visited again and the patients were lost to follow-up. Conclusions Our observations of patients with severe schistosomiasis document the severe degree of endemicity of S. mansoni in the province and suggest an urgent need for adequate schistosomiasis control measures that target vulnerable population groups and address severe complications.

BackgroundControlling morbidity is the main target of schistosomiasis control. Yet only rarely do we assess morbidity linked to Schistosoma sp. infection. In the Democratic Republic of Congo (DRC), and particularly in the north-eastern Ituri province, morbidity associated with Schistosoma mansoni infection is unknown. For this reason, we aimed to assess intestinal and hepatosplenic morbidity associated with S. mansoni infection in Ituri province.Methods / Principal FindingsIn 2017, we conducted a cross-sectional study in 13 villages in Ituri province, DRC. S. mansoni infection was assessed with a Kato-Katz stool test (2 smears) and a point-of-care circulating cathodic antigen (POC-CCA) test in urine. A questionnaire was used to obtain demographic data and information about experienced intestinal morbidity. Each participant underwent an abdominal ultrasonography examination to diagnose hepatosplenic morbidity. Of the 586 study participants, 76.6% tested positive for S. mansoni. Intestinal morbidity, such as abdominal pain (52.7%), diarrhoea (23.4%) and blood in the stool (21.5%) in the previous two weeks, was very frequent. Hepatosplenic morbidity was demonstrated by abnormal liver parenchyma patterns (42.8%), hepatomegaly (26.5%), and splenomegaly (25.3%). Liver pathology (adjusted odds ratio [aOR] 1.20, 95% confidence interval [CI] 1.06–1.37, P=0.005) was positively and significantly associated with S. mansoni infection. Hepatomegaly (aOR 1.52, 95% confidence interval [CI] 0.99–2.32, P=0.053) and splenomegaly (aOR 1.12, 95% CI 0.73–1.72, P=0.619) were positively but not significantly associated with S. mansoni infection at the individual level. At the village level, S. mansoni prevalence was positively associated with the prevalence of hepatomegaly and splenomegaly. Higher S. mansoni infection intensities were associated with diarrhoea, blood in the stool, hepatomegaly, splenomegaly and with liver parenchyma, pathology patterns C, D, E and F. Four study participants were diagnosed with ascites and five reported hematemesis.Conclusions/SignificanceOur study documents a high burden of intestinal and hepatosplenic morbidity associated with S. mansoni infection status in Ituri province. The results call for targeted interventions to address both S. mansoni infection and related morbidity.Author SummarySchistosomiasis caused by Schistosoma mansoni is of great public health importance in sub-Saharan Africa. The World Health Organization (WHO) recommends that control efforts aim to reduce morbidity through large scale intervention programmes. However, intestinal and liver morbidity is rarely assessed in such control programmes. Hence, little is known about (i) the magnitude of the intestinal and liver morbidity burden in each community, or about (ii) the morbidity associated with S. mansoni infection, specifically. We conducted a (cross-sectional) study in which we assessed intestinal morbidity by questionnaire and liver morbidity by abdominal ultrasonography. Further, we determined the infection status of the study participants using standard diagnostic procedures (Kato-Katz technique and point-of-care cathodic circulating S. mansoni antigen [POC-CCA] test in urine). Among 586 study participants, six years and older, from 13 villages in Ituri province, DRC, we observed a high degree of intestinal (e.g. 23.4% with diarrhoea, 21.5% with blood in stool) and hepatosplenic morbidity (e.g. 42.8% with abnormal liver patterns C, D, E, and F, 26.5% with enlarged liver, 25.3% with enlarged spleen). S. mansoni infection was associated with liver and spleen enlargement. Likewise, S. mansoni infection intensity was linked to diarrhoea, to liver and spleen enlargement and to pathological changes in the liver parenchyma. At village level, we observed that the prevalence of enlarged liver and spleen among patients increased with the prevalence of S. mansoni infection. We conclude that the population of Ituri province carries an alarming burden of intestinal, liver and spleen morbidity associated with S. mansoni infection. Therefore, a comprehensive control programme to address this infection and disease burden is urgently required.

Rapid progress in micro- and nanotechnologies such as lab-on-a-chip (microfluidic networks, sensors, actuators, and connectors), soft lithography (replica moulding, microcontact printing and affinity contact printing), and stretchable transparent electronics has strongly benefitted from high-performance polymers like poly(dimethyl)siloxane (PDMS) that are suited for high-fidelity microsystem construction and rapid prototyping. While basic PDMS has been a unique enabling material, recent progress in tailoring PDMS to specific requirements will render this material even more valuable in the future. Basic PDMS is elastic, transparent, biocompatible, gas-permeable, and forms conformal contact with surfaces. Surface modifications of PDMS, inducing properties such as hydrophilicity, electrical conductivity, anti-fouling, energy harvesting, and energy storage (supercapacitors) are of major interest. Bulk modifications can alter PDMS properties such as elasticity, electrical and thermal conductivity. Such bulk modified PDMS composite materials can be created by embedding free molecules (e.g., dyes), nanoparticles (graphene, carbon nanotubes, and various other of organic and inorganic nature) or microparticles, or by altering the composition of the prepolymers before polymerization. Both, surface and bulk modifications of PDMS open avenues to a multitude of tuneable characteristics optimized for a diverse set of applications ranging from integrated micro- (lab-on-a-chip) to macro-systems (biomedical devices and epidermal electronics). In microfluidic systems design exploiting modified PDMS, a key aspect of this review, the unique features of these materials permit rapid, easy, and reproducible construction without the need for elaborate facilities and trained personnel as compared to other materials like silicon. This review focuses on recent progress in modification strategies to alter deliberately PDMS surface and bulk properties, especially for microfluidic, biological, flexible electronics, e-skin, and self-healing applications.

Due to the progressive spread of the dengue virus and a rising incidence of dengue disease, its rapid diagnosis is important for developing countries and of increasing relevance for countries in temperate climates. Recent advances in bioelectronics, micro- and nanofabrication technologies have led to new miniaturized point-of-care devices and analytical platforms suited for rapid detection of infections. Starting from the available tests for dengue diagnosis, this review examines emerging rapid, micro/nanotechnologies-based tools, including label-free biosensor methods, microarray and microfluidic platforms, which hold significant potential, but still need further development and evaluation. The epidemiological and clinical setting as key determinants for selecting the best analytical strategy in patients presenting with fever is then discussed. This review is aimed at the clinicians and microbiologists to deepen understanding and enhance application of dengue diagnostics, and also serves as knowledge base for researchers and test developers to overcome the challenges posed by this disease. From the Clinical Editor Dengue disease remains a significant problem in many developing countries. Unfortunately rapid diagnosis with easy and low cost tests for this disease is currently still not realized. In this comprehensive review, the authors highlighted recent advances in nanotechnology which would enable development in this field, which would result in beneficial outcomes to the population.

The electrokinetic transport behavior of lambda-DNA (48 kbp) in 20 nm-high fused-silica nanoslits in the presence of short-chain PVP is investigated. Mobility and video data show a number of phenomena that are typical of DNA transport through gels or polymer solutions, thus indicative of rigid migration obstacles in the DNA pathway. Calculations show that a several nanometer thin layer of wall-adsorbed PVP ('nano-gel') can provide such a rigid obstacle matrix to the DNA. Such ultrathin wall-adsorbed polymer layers represent a new type of matrix for electrokinetic DNA separation.

The development of nanostructure devices has opened the door to new DNA separation techniques and fundamental investigations. With advanced nanotechnologies, artificial gels (e.g. nanopillar arrays, nanofilters) can be manufactured with controlled and ordered geometries. This contrast with gels, where the pores are disordered and the range of available pore sizes is limited by the level of cross-linking and the mechanical properties of the gel. In this review, we recall the theories developed for free-solution and gel electrophoresis (extended Ogston model, biased reptation and entropic trapping) and from this perspective, suggestions for future concepts for fast DNA separation using nanostructures will be given.

The transport behavior of lambda-DNA (48 kbp) in fused silica nanoslits is investigated upon application of electrical fields of different strengths. The slit dimensions are 20 nm in height, 3 microm in width, and 500 microm in length. With fields of 30 kV/m or below, the molecules move fluently through the slits, while at higher electrical fields, the DNA molecules move intermittently, resulting in a strongly reduced mobility. We propose that the behavior can be explained by mechanical and/or field-induced dielectrophoretic DNA trapping due to the surface roughness in the nanoslits. The observation of preferential pathways and trapping sites of the lambda-DNA molecules through the nanoslits supports this hypothesis and indicates that the classical viscous friction models to explain the DNA movement in nanoslits needs to be modified to include these effects. Preliminary experiments with the smaller XbaI-digested litmus-DNA (2.8 kbp) show that the behavior is size-dependent, suggesting that the high field electrophoresis in nanoslits can be used for DNA separation.

Sensitive, specific and rapid diagnosis of infectious diseases is essential for effective and economic medical care. Focused medical treatment of the patient enabled by pathogen-specific diagnosis may benefit the patient, may reduce cost, and may minimize the risk of drug resistance development. The rapid progress in micro and nanotechnologies contributes to the development of novel diagnostic methods. This critical review assesses emerging nanotechnologies for diagnosis of bacterial infection in developed and developing countries on the background of the current state of the art and includes particular challenges and pitfalls posed by a number of specific pathogens.

This paper reports a novel approach for the formation of anti-inflammatory surface coating on a neural electrode. The surface coating is realized using a recombinant f88 filamentous bacteriophage, which displays a short platinum binding motif and a tumor necrosis factor alpha antagonist (TNF-α antagonist) on p3 and p8 proteins, respectively. The recombinant bacteriophages are immobilized on the platinum surface by a simple dip coating process. The selective and stable immobilization of bacteriophages on a platinum electrode is confirmed by quartz crystal microbalance with dissipation monitoring, atomic force microscope and fluorescence microscope. From the in vitro cell viability test, the inflammatory cytokine (TNF-α) induced cell death was prevented by presenting recombinant bacteriophage coating, albeit with no significant cytotoxic effect. It is also observed that the bacteriophage coating does not have critical effects on the electrochemical properties such as impedance and charge storage capacities. Thus, this approach demonstrates a promising anti-apoptotic as well as anti-inflammatory surface coating for neural implant applications.

Rapid, specific and sensitive diagnosis of infec- tious diseases is important for the rational, effective and economic treatment of the infection. Focused treatment of the patient with an accurate diagnosis may also contrib- ute to the minimization of drug resistance development. Rapidly evolving micro and nanotechnologies contribute to the development of new diagnostic modalities. This critical review provides an overview of current develop- ments in diagnostics for infectious disease enabled by nanotechnologies and includes a range of representative examples.

The paper gives a brief overview of nanofluidic theory, with an emphasis on transport processes in nanochannels. It subsequently reports on recent progress in nanofluidic research in the BIOS/Lab-on-a-Chip group, especially DNA electrophoresis in 20-nm high nanoslits, AC electroosmotic flow in nanochannels, and two-phase flow in nano/microfluidic devices.

Contains fulltext : 51378.pdf (Publisher’s version ) (Closed access) The H19 differentially methylated region (DMR) controls the allele-specific expression of both the imprinted H19 tumor-suppressor gene and the IGF2 growth factor. Hypermethylation of this DMR--and subsequently of the H19 promoter region--is a major cause of the clinical features of gigantism and/or asymmetry seen in Beckwith-Wiedemann syndrome or in isolated hemihypertrophy. Here, we report a series of patients with hypomethylation of the H19 locus. Their main clinical features of asymmetry and growth retardation are the opposite of those seen in patients with hypermethylation of this region. In addition, we show that complete hypomethylation of the H19 promoter is found in two of three patients with the full clinical spectrum of Silver-Russell syndrome. This syndrome is also characterized by growth retardation and asymmetry, among other clinical features. We conclude that patients with these clinical features should be analyzed for H19 hypomethylation.

Microfluidic systems represent a key-enabling platform for novel diagnostic tools for use at the point-of-care in clinical contexts as well as for evolving single cell diagnostics. The design of 3D microfluidic systems is an active field of development, but construction of true interconnected 3D microfluidic networks is still a challenge, in particular when the goal is rapid prototyping, accurate design and flexibility. We report a novel approach for the construction of programmable 3D microfluidic systems consisting of modular 3D template casting of interconnected threads to allow user-programmable flow paths and examine its structural characteristics and its modular function. To overcome problems with thread template casting reported in the literature, low-surface-energy polymer threads were used, that allow solvent-free production. Connected circular channels with excellent roundness and low diameter variability were created. Variable channel termination allowed programming a flow path on-the-fly, thus rendering the resulting 3D microfluidic systems highly customizable even after production. Thus, construction of programmable/reprogrammable fully 3D microfluidic systems by template casting of a network of interconnecting threads is feasible, leads to high-quality and highly reproducible, complex 3D geometries.

Capillary malformations (port-wine stains) are the most common vascular malformations occurring in 0.3% of live births. Most capillary malformations occur sporadically and present as a solitary lesion. Capillary malformations can also occur as a component of well-described syndromes. Familial occurrence of multiple capillary malformations has been described in the literature, suggesting autosomal dominant inheritance with variable expression in this subgroup. A hereditary basis underlying the development of solitary capillary malformations has not been found, but may well be possible. We have mapped a locus for an autosomal dominant disorder in a three-generation family that manifested itself with multiple cutaneous capillary malformations to chromosome 5q13-22. This locus spans 48 cM between the markers D5S647 and D5S659 and harbours several candidate genes. By defining the gene(s) responsible for capillary malformations, we will gain more insight in the pathogenesis of this disorder. It is likely that genes implicated in these familial cases may be involved in the more sporadic cases.