Impact of surgical intervention on progression to end-stage renal disease in patients with posterior urethral valve.

BACKGROUND: Posterior urethral valve patients present with varied presentations at any age of life and have significant associated morbidity and require long-term follow-up and care. METHODS: This was a single-center ambispective cohort study carried out over a period of 2 years. Patient data regarding the symptoms, investigations, interventions, secondary complications were recorded and were followed up regularly during the study till either normalization of their creatinine level which was maintained up to one-year post-fulguration (non-CKD) or progression to end-stage renal disease (ESRD) requiring renal transplant. Various clinical factors were then compared between these groups. RESULTS: The age of presentation varies from 6 months antenatal period to a maximum of 34 years. Most common symptom was of lower urinary tract obstruction, followed by recurrent febrile UTI. The interval between disease presentation detection and PU valve fulguration ranged from 6 days to more than 5 years, median duration being 1 month. 85.7% patients had hydroureteronephrosis on initial USG. In VCUG, there was no significant difference found between the presence of reflux and poor renal outcome. Age of presentation greater than 2 years was seen in 52% of patients with CKD compared to only 10% patients in non-CKD group (significant, p value 0.02). Among patients who developed CKD, 60% of patients had PU valve fulguration after one month of disease presentation, while in contrast, among the non-CKD group, 80% of patients had it done within one month of disease presentation. (significant, p value 0.03). CONCLUSIONS: Late age of presentation, delayed fulguration with high initial creatinine, and failure of serum creatinine to return to normal after one-month post-fulguration are important risk factors in the progression of the disease to ESRD. Symptomatic improvement after interventions does not correlate with progression to ESRD. The number of interventions also does not predict progression to ESRD. Interventions should be chosen wisely on case to restore near-normal physiology and delay progression to ESRD.

Author Correction: Energetic costs regulated by cell mechanics and confinement are predictive of migration path during decision-making.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Energetic costs regulated by cell mechanics and confinement are predictive of migration path during decision-making.

Cell migration during the invasion-metastasis cascade requires cancer cells to navigate a spatially complex microenvironment that presents directional choices to migrating cells. Here, we investigate cellular energetics during migration decision-making in confined spaces. Theoretical and experimental data show that energetic costs for migration through confined spaces are mediated by a balance between cell and matrix compliance as well as the degree of spatial confinement to direct decision-making. Energetic costs, driven by the cellular work needed to generate force for matrix displacement, increase with increasing cell stiffness, matrix stiffness, and degree of spatial confinement, limiting migration. By assessing energetic costs between possible migration paths, we can predict the probability of migration choice. Our findings indicate that motility in confined spaces imposes high energetic demands on migrating cells, and cells migrate in the direction of least confinement to minimize energetic costs. Therefore, therapeutically targeting metabolism may limit cancer cell migration and metastasis.

Integration of sample preparation and analysis into an optofluidic chip for multi-target disease detection.

Detection of molecular biomarkers with high specificity and sensitivity from biological samples requires both sophisticated sample preparation and subsequent analysis. These tasks are often carried out on separate platforms which increases required sample volumes and the risk of errors, sample loss, and contamination. Here, we present an optofluidic platform which combines an optical detection section with single nucleic acid strand sensitivity, and a sample processing unit capable of on-chip, specific extraction and labeling of nucleic acid and protein targets in complex biological matrices. First, on-chip labeling and detection of individual lambda DNA molecules down to concentrations of 8 fM is demonstrated. Subsequently, we demonstrate the simultaneous capture, fluorescence tagging and detection of both Zika specific nucleic acid and NS-1 protein targets in both buffer and human serum. We show that the dual DNA and protein assay allows for successful differentiation and diagnosis of Zika against cross-reacting species like dengue.

Scalable Spatial-Spectral Multiplexing of Single-Virus Detection Using Multimode Interference Waveguides.

Simultaneous detection of multiple pathogens and samples (multiplexing) is one of the key requirements for diagnostic tests in order to enable fast, accurate and differentiated diagnoses. Here, we introduce a novel, highly scalable, photonic approach to multiplex analysis with single virus sensitivity. A solid-core multimode interference (MMI) waveguide crosses multiple fluidic waveguide channels on an optofluidic chip to create multi-spot excitation patterns that depend on both the wavelength and location of the channel along the length of the MMI waveguide. In this way, joint spectral and spatial multiplexing is implemented that encodes both spatial and spectral information in the time dependent fluorescence signal. We demonstrate this principle by using two excitation wavelengths and three fluidic channels to implement a 6x multiplex assay with single virus sensitivity. High fidelity detection and identification of six different viruses from a standard influenza panel is reported. This multimodal multiplexing strategy scales favorably to large numbers of targets or large numbers of clinical samples. Further, since single particles are detected unbound in flow, the technique can be broadly applied to direct detection of any fluorescent target, including nucleic acids and proteins.

Integrated hollow fiber membranes for gas delivery into optical waveguide based photobioreactors.

Compact algal reactors are presented with: (1) closely stacked layers of waveguides to decrease light-path to enable larger optimal light-zones; (2) waveguides containing scatterers to uniformly distribute light; and (3) hollow fiber membranes to reduce energy required for gas transfer. The reactors are optimized by characterizing the aeration of different gases through hollow fiber membranes and characterizing light intensities at different culture densities. Close to 65% improvement in plateau peak productivities was achieved under low light-intensity growth experiments while maintaining 90% average/peak productivity output during 7-h light cycles. With associated mixing costs of ∼ 1 mW/L, several magnitudes smaller than closed photobioreactors, a twofold increase is realized in growth ramp rates with carbonated gas streams under high light intensities, and close to 20% output improvement across light intensities in reactors loaded with high density cultures.

Optimal intensity and biomass density for biofuel production in a thin-light-path photobioreactor.

Production of competitive microalgal biofuels requires development of high volumetric productivity photobioreactors (PBRs) capable of supporting high-density cultures. Maximal biomass density supported by the current PBRs is limited by nonuniform distribution of light as a result of self-shading effects. We recently developed a thin-light-path stacked photobioreactor with integrated slab waveguides that distributed light uniformly across the volume of the PBR. Here, we enhance the performance of the stacked waveguide photobioreactor (SW-PBR) by determining the optimal wavelength and intensity regime of the incident light. This enabled the SW-PBR to support high-density cultures, achieving a carrying capacity of OD730 20. Using a genetically modified algal strain capable of secreting ethylene, we improved ethylene production rates to 937 µg L(-1) h(-1). This represents a 4-fold improvement over a conventional flat-plate PBR. These results demonstrate the advantages of the SW-PBR design and provide the optimal operational parameters to maximize volumetric production.

Stacked optical waveguide photobioreactor for high density algal cultures.

In this work, an ultracompact algal photobioreactor that alleviates the problem of non-optimal light distribution in current algae photobioreactor systems, by incorporating stacked layers of slab waveguides with embedded light scatterers, is presented. Poor light distribution in traditional photobioreactor systems, due to self-shading effects, is responsible for relatively low volumetric productivity. The optimal conditions for operating a 10-layer bioreactor are outlined. The bioreactor exhibits the ability to sustain uniform biomass growth throughout the bioreactor for 3 weeks, and demonstrates an 8-fold increase in biomass productivity. Using a genetically engineered algal strain, constant secreted ethylene production for over 45 days is also demonstrated. Since the stacked architecture leads to improved light distribution throughout the volume of the bioreactor, it reduces the need for culture mixing for optimum light distribution, and thereby potentially reducing operational costs.

In situ UV disinfection of a waveguide-based photobioreactor.

Compact waveguide-based photobioreactors with high surface area-to-volume ratios and optimum light-management strategies have been developed to achieve high volumetric productivities within algal cultures. The light-managing strategies have focused on optimizing sunlight collection, sunlight filtration, and light delivery throughout the entire bioreactor volume by using light-directing waveguides. In addition to delivering broad-spectrum or monochromatic light for algal growth, these systems present an opportunity for advances in photobioreactor disinfection by using germicidal ultraviolet (UV) light. Here, we investigated the efficacy of in situ, nonchemical UV treatment to disinfect a heterotrophic contaminant in a compact photobioreactor. We maintained a >99% pure culture of Synechocystis sp. PCC 6803 for an operating period exceeding 3 weeks following UV treatment of an intentionally contaminated waveguide photobioreactor. Without UV treatment, the culture became contaminated within only a few days (control). We developed a theoretical model to predict disinfection efficiency based on operational parameters and bioreactor geometry, and we verified it with experimental results to predict the disinfection efficiency of a Bacillus subtilis spore culture.

Optofluidic opportunities in global health, food, water and energy.

Optofluidics is a rapidly advancing field that utilizes the integration of optics and microfluidics to provide a number of novel functionalities in microsystems. In this review, we discuss how this approach can potentially be applied to address some of the greatest challenges facing both the developing and developed world, including healthcare, food shortages, malnutrition, water purification, and energy. While medical diagnostics has received most of the attention to date, here we show that some other areas can also potentially benefit from optofluidic technology. Whenever possible we briefly describe how microsystems are currently used to address these problems and then explain why and how optofluidics can provide better solutions. The focus of the article is on the applications of optofluidic techniques in low-resource settings, but we also emphasize that some of these techniques, such as those related to food production, food safety assessment, nutrition monitoring, and energy production, could be very useful in well-developed areas as well.

Gel-based optical waveguides with live cell encapsulation and integrated microfluidics.

In this Letter, we demonstrate a biocompatible microscale optical device fabricated from agarose hydrogel that allows for encapsulation of cells inside an optical waveguide. This allows for better interaction between the light in the waveguide and biology, since it can interact with the direct optical mode rather than the evanescent field. We characterize the optical properties of the waveguide and further incorporate a microfluidic channel over the optical structure, thus developing an integrated optofluidic system fabricated entirely from agarose gel.