The widespread distribution of smartphones, with their integrated sensors and communication capabilities, makes them an ideal platform for point-of-care (POC) diagnosis, especially in resourcelimited settings. Molecular diagnostics, however, have been difficult to implement in smartphones. We herein report a diffractionbased approach that enables molecular and cellular diagnostics. The D3 (digital diffraction diagnosis) system uses microbeads to generate unique diffraction patterns which can be acquired by smartphones and processed by a remote server. We applied the D3 platform to screen for precancerous or cancerous cells in cervical specimens and to detect human papillomavirus (HPV) DNA. The D3 assay generated readouts within 45 min and showed excellent agreement with gold-standard pathology or HPV testing, respectively. This approach could have favorable global health applications where medical access is limited or when pathology bottlenecks challenge prompt diagnostic readouts.T he rapid dissemination of electronic communication devices such as smartphones, tablets, and wearable electronics, all with integrated sensors, creates new possibilities for inexpensive point-of-care (POC) diagnostics and care delivery. One example is detecting cancer in low-and middle-income countries where limited resources and geographical constraints often lead to missed opportunities for intervention, resulting in mortalities even with treatable cancers (1). Current efforts to control cancer thus focus on implementing population-based early screening programs; a key element for success is a cost-effective, robust diagnostic platform that can be readily deployed into POC settings (2). Whereas conventional microscopy of human samples (smears, aspirates, biopsies, blood) is the most widely used to diagnose cancer, its POC adaptation is limited by inherent drawbacks such as bulky optics, requirements for trained microscopists, and operatordependent variability.Recent advances in digital sensors and computational approaches have introduced new microscopy techniques. Digital holography, in particular, has emerged as one alternative to conventional bright-field microscopy. Following the initial description of lens-free holography by Kreuzer's group (3), various diffractionbased imaging systems have been developed (4-8). The majority of recent work, however, is based on identifying targets by their inherent morphology (e.g., blood cells, bacteria, Caenorhabditis elegans) (4, 9-14). We reasoned that it would be possible to impart molecular specificity to improve disease detection and phenotyping akin to other molecular profiling strategies (15, 16).Here we describe a digital diffraction diagnostics (D3)-a computational analysis of distinct diffraction patterns generated by microbeads that bind to biological target of interest. The strategy can detect a broad range of targets (SI Appendix, Table S1): soluble proteins, nucleic acids, or cellular proteins. To provide effective POC operation at remote sites, we adopted a client-server model:...

Background Isoflurane may be protective in pre-clinical models of lung injury but its use in patients with lung injury remains controversial and the mechanism of its protective effects remains unclear. We hypothesized that this protection is mediated at the level of alveolar tight junctions and investigated the possibility in a two-hit model of lung injury that mirrors human acute respiratory distress syndrome. Methods Wild-type mice were treated with isoflurane one hour after exposure to nebulized endotoxin (n=8) or saline control (n=9) then allowed to recover for 24 hrs prior to mechanical ventilation (MV, tidal volume 15 mL/kg, 2 hrs) producing ventilator-induced lung injury. Mouse lung epithelial cells were similarly treated with isoflurane one hour after exposure to lipopolysaccharide. Cells were cyclically stretched the following day to mirror the MV protocol used in vivo. Results Mice treated with isoflurane following exposure to inhaled endotoxin and prior to MV exhibited significantly less physiologic lung dysfunction. These effects appeared to be mediated by decreased vascular leak, but not altered inflammatory indices. Mouse lung epithelial cells treated with lipopolysaccharide and cyclic stretch and lungs harvested from mice following treatment with lipopolysaccharide and MV had decreased levels of a key tight junction protein (i.e. zona occludens 1) that was rescued by isoflurane treatment. Conclusions Isoflurane rescued lung injury induced by a two-hit model of endotoxin exposure followed by MV by maintaining the integrity of the alveolar-capillary barrier possibly by modulating the expression of a key tight junction protein.

Objective Assess the effect of class III (body mass index [BMI, kg/m 2 ] 40-49.9) and class IV obesity (≥ 50) on clinical pregnancy and live birth outcomes after first oocyte retrieval and fresh embryo transfer cycle. Design Cohort study Setting Academic center Patients Patients undergoing their first oocyte retrieval with planned fresh embryo transfer in our clinic between 01/01/2012 and 12/31/2018. Patients were stratified by BMI: 18.5-24.9 (n = 4913), 25-29.9 (n = 1566) 30-34.9 (n = 559), 35-39.9 (n = 218), and ≥ 40 (n = 114). Intervention None Main outcome measure Live birth rate Results Following embryo transfer, there were no differences in pregnancy rates across all BMI groups (p value, linear trend = 0.86). However among pregnant patients, as BMI increased, a significant trend of a decreased live birth rate was observed (p value, test for linear trend = 0.004). Additionally, as BMI increased, a significant trend of an increased miscarriage rate was observed (p value, linear trend = < 0.001). Compared to the normal-weight cohort, women with a BMI ≥ 40 had a significantly higher rate of cancelled fresh transfers after retrieval (18.4% vs. 8.2%, OR 2.51; 95%CI 1.55-4.08). Among singleton deliveries, a significant trend of an increased c-section rate was identified as the BMI increased (p value, linear trend = <0.001). Conclusion Overall, patients with a BMI > 40 have worse IVF treatment outcomes compared to normal-weight patients. After embryo transfer, their pregnancy rate is comparable to normal-weight women; however, their miscarriage rate is higher, leading to a lower live birth rate for pregnant women in this population. Patients with a BMI > 40 have a c-section rate that is 50% higher than normal-weight patients.