Effect of UV-light exposure duration, light source, and aging on nitroguanidine (NQ) degradation product profile and toxicity.

Previous studies have reported increased aquatic toxicity of UV-degraded nitroguanidine (NQ), but many details underlying the dynamics of NQ degradation and toxicity remain unknown. These data gaps represent critical barriers to assessing the environmental relevance of laboratory-generated UV-degradation results and extrapolation to environmental risk. In the present study, the toxicity of NQ increased with increasing proportional degradation of the parent compound. Specifically, while the LC50 of undegraded NQ was 1485 mg/L, the toxicity at the lowest degradation level examined (7% parent compound degraded) increased by nearly two-orders of magnitude (LC50 = 17.3 mg/L) and increased by nearly three-orders of magnitude (LC50 = 6.23 mg/L) in the highest percent NQ degradation (90%) treatment. Similar LC50 values between immediately tested and aged (8-13 days) NQ degradation products suggested the degradation product(s) causing the toxicity were stable, although concentrations of nitrite and nitrate increased after aging. Finally, experiments where NQ was degraded in natural sunlight confirmed increased toxicity in environmentally relevant D. pulex exposures; however, the two-order of magnitude increase in toxicity (LC50 = 21.3 mg/L) at 53% degradation was less than NQ degraded by a laboratory photoreactor by a similar percentage (46% degraded). Identification of principal toxic agents in the UV-degraded NQ product mixture remains a critical data gap. Mass balance calculations were generated for our experimental results and literature values revealing difficulty in accounting for all NQ degradation products. Products with suspected high potency in D. pulex were identified which require further testing including: nitrosoguanidine, nitrosourea, and hydroxylamine. SYNOPSIS: The toxicity of NQ increased with increasing UV-degradation where toxicity-inducing degradation products were stable over 1-2 weeks; increased toxicity was validated from natural-sunlight degradation of NQ, however toxicity was lower than UV-photoreactor degraded NQ; and the identity of specific toxic UV-degradation products remains elusive where carefully-designed mass-balance experiments and toxicity testing are needed to provide definitive identification.

Is there a difference in outcomes between the first and second surgical procedures in patients who have bilateral shoulder operations?

BACKGROUND: Some patients who have shoulder surgery on 1 shoulder go on to have surgery on their contralateral shoulder. It is unclear whether the clinical improvements following the second surgical procedure are as significant as the improvements after the first surgical procedure. METHODS: All patients who underwent surgery on both shoulders performed by a single surgeon between March 2013 and June 2018 were eligible for inclusion. Visual analog scale (VAS) scores were obtained preoperatively and at 2 weeks, 6 weeks, 3 months, 6 months, 1 year, and 2 years for both shoulders. Scores were then compared based on hand dominance and which shoulder was treated first. Complications were also recorded. RESULTS: Overall, 105 patients (210 surgical procedures) were included. Of the patients, 66 underwent bilateral open shoulder surgery and 39 underwent bilateral arthroscopic shoulder surgery. There was a significant reduction in VAS scores from preoperative to postoperative levels following surgery (5.9 before surgery vs. 1.7 after surgery). We found no difference in VAS scores at any time point when comparing whether the dominant or nondominant shoulder was operated on first. Significantly higher VAS scores were observed at 2 weeks, 6 weeks, and 3 months following the first shoulder operation compared with the second; by 6 months and beyond, there was no longer a difference. CONCLUSION: Patients who undergo bilateral shoulder surgery have more pain in the first 3 months following their first shoulder operation compared with their second. However, there is no difference in pain scores at 6 months and beyond between shoulders.

Clinical and radiographic outcomes after Latarjet using suture-button fixation.

BACKGROUND: Latarjet has become a common treatment option for patients with shoulder instability in the setting of bone loss. The coracoid is commonly secured with screws. METHODS: All patients who underwent Latarjet with suture-button fixation with minimum 1-year follow-up were eligible for inclusion. Preoperative demographic and clinical outcome data including American Shoulder and Elbow Surgeons (ASES), Single Assessment Numerical Evaluation (SANE), and Visual Analog Scale (VAS) were recorded and compared with postoperative scores. Radiographs were reviewed for signs of nonunion. Complications were recorded. RESULTS: Overall 21 patients (76% male, average age: 30.4 ± 11.3 years) underwent Latarjet with suture-button fixation. Significant improvements at 1 year were seen in ASES (P < 0.001), SANE (P < 0.001), and VAS (P = 0.011) scores compared with preoperative scores. Of the 21 patients who had reached 1-year follow-up, 17 (81%) reached 2-year follow-up. For the 17 patients who reached 2-year follow-up, there were significant improvements in ASES (P = 0.001), SANE (P = 0.001), and VAS (P = 0.005) scores from preoperative values. When isolating the 17 patients with 2-year follow-up, there were no significant differences between their 1-year and 2-year ASES (P = 0.73), SANE (P = 0.17), and VAS (P = 0.37) scores. Overall, 3 patients (14%) sustained a complication (one redislocation, one with coracoid migration and a fibrous union, and one superior labral tear requiring biceps tenodesis and superior labral repair). CONCLUSION: Suture-button fixation of the coracoid during the Latarjet provides encouraging clinical and radiographic outcomes at 1 and 2 years.

Massive and Microscopic: Autoethnographic Affects in the Time of COVID.

This essay uses several of the prompts from the Massive::Microscopic experiment as a jumping off point for considering how affect theory and critical autoethnography offer us a framework for understanding, creating, and acting together in the time of COVID. Through stories of cloud-watching, mindfulness meditation, and other encounters with atmospheres and movements, we connect individual experiences of the pandemic to Buddhist understandings of a universal "we." As a research practice committed to joining microscopic with macro lived experience, critical autoethnography offers a speculative method for collective reckoning with our infinitesimal selves in relation to the infinite of a pandemic.

Outpatient versus inpatient anatomic total shoulder arthroplasty: outcomes and complications.

BACKGROUND: Total shoulder arthroplasty (TSA) is an effective treatment option for glenohumeral arthritis. Historically, this surgical procedure was performed on an inpatient basis. There has been a recent trend in performing TSA on an outpatient basis in the proper candidates. METHODS: All patients who underwent outpatient TSA performed by a single surgeon between 2015 and 2017 were included. Demographic information and clinical outcome scores, as well as data on complications, readmissions, and revision surgical procedures, were recorded. This group of patients was then compared with a matched cohort of patients who underwent inpatient TSA over the same period. RESULTS: Overall, 94 patients (average age, 60.4 years; 67.0% male patients) underwent outpatient TSA and were included. Patients who underwent outpatient TSA showed significant improvement in all clinical outcome scores at both 1 and 2 years postoperatively. The control group consisted of 77 patients who underwent inpatient TSA (average age, 62.6 years; 53.2% male patients). No significant differences in complications or improvements in clinical outcome scores were found between the inpatient and outpatient groups. CONCLUSION: TSA performed in an outpatient setting is a safe and reliable procedure that provides significant improvement in clinical outcome scores and no difference in complication rates compared with inpatient TSA.

Subscapularis Repair During Reverse Total Shoulder Arthroplasty Using a Stem-Based Double-Row Repair: Sonographic and Clinical Outcomes.

BACKGROUND: Treatment of the subscapularis in reverse total shoulder arthroplasty (RTSA) is a controversial topic, with conflicting evidence regarding outcomes after repair. PURPOSE/HYPOTHESIS: The purpose of this study was to report clinical and sonographic outcomes of a through-implant double-row suture technique for subscapularis repair in RTSA and to compare clinical outcomes and range of motion (ROM) between patients with an intact subscapularis tendon repair versus those whose tendon repair was not intact. The authors hypothesized that the novel repair technique would find more than 80% of tendons intact on ultrasound, with significant improvement in clinical outcome scores and ROM. The authors also hypothesized that patients with an intact subscapularis tendon repair would have better clinical outcomes compared with those with a nonintact tendon repair. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The study included all patients who underwent RTSA by 1 of 2 surgeons between August 2016 and March 2017 with the through-implant double-row suture technique for subscapularis repair. Subscapularis tendon integrity was assessed postoperatively via ultrasound at minimum 1-year follow-up. American Shoulder and Elbow Surgeons (ASES), Single Assessment Numeric Evaluation (SANE), and pain visual analog scale (VAS) scores were recorded at the final follow-up visit in addition to ROM measures. RESULTS: A total of 48 patients (31 males, 17 females; mean age, 68.9 ± 7.4 years; mean follow-up, 13.8 ± 2.1 months) were included. On ultrasound, the subscapularis was intact in 83.3% of patients. Regarding preoperative versus postoperative outcome scores, the ASES score (mean ± SD) significantly improved from 38.3 ± 14.7 to 81.9 ± 13.6, the SANE score significantly improved from 29.8 ± 24.2 to 75.5 ± 21.0, and the VAS pain score significantly improved from 5.9 ± 2.1 to 1.2 ± 1.6 (P < .001 for all). Forward flexion and external rotation significantly improved. No significant difference existed in clinical outcome scores or ROM between patients with intact versus torn subscapularis tendons based on ultrasound. CONCLUSION: Subscapularis repair using a stem-based double-row repair technique during RTSA demonstrated an overall healing rate of 83.3%, as evidenced by ultrasound examination at short-term follow-up. Integrity of subscapularis repair did not affect clinical outcome or ROM.

Outpatient vs. inpatient reverse total shoulder arthroplasty: outcomes and complications.

BACKGROUND: Reverse total shoulder arthroplasty (RTSA) is an effective treatment option for many shoulder conditions. Historically, this surgical procedure was performed on an inpatient basis. There has been a recent trend to perform RTSA on an outpatient basis in proper candidates. METHODS: All patients who underwent outpatient RTSA performed by a single surgeon between 2015 and 2017 were included. Demographic information and clinical outcome scores (American Shoulder and Elbow Surgeons, visual analog scale, and Single Assessment Numeric Evaluation scores), as well as data on complications, readmission, and revision surgery, were recorded. This group of patients was then compared with a cohort of patients who underwent RTSA in the inpatient setting during the same period. RESULTS: Overall, 241 patients (average age, 68.9 years; 52.3% female patients) underwent outpatient RTSA and were included. Patients who underwent outpatient RTSA showed significant improvements in all clinical outcome scores at both 1 and 2 year postoperatively (all P < .0001). The control group of patients who underwent RTSA as inpatients consisted of 373 patients (average age, 72 years; 66% female patients). Significantly more controls had diabetes (P = .007), and controls had a higher body mass index (P = .022). No significant differences existed in improvements in clinical outcome scores between the inpatient and outpatient groups. Complication rates were significantly lower for outpatient cases than for inpatient controls (7.0% vs. 12.7%, P = .023). CONCLUSION: RTSA performed in an outpatient setting is a safe and reliable procedure that provides significant improvements in clinical outcome scores with fewer complications compared with inpatient RTSA.

Identifying degradation products responsible for increased toxicity of UV-Degraded insensitive munitions.

Degradation of insensitive munitions (IMs) by ultraviolet (UV) light has become a topic of concern following observations that some UV-degradation products have increased toxicity relative to parent compounds in aquatic organisms. The present investigation focused on the Army's IM formulation, IMX-101, which is composed of three IM constituents: 2,4-dinitroanisole (DNAN), 3-nitro-1,2,4-triazol-5-one (NTO), and nitroguanidine (NQ). The IM constituents and IMX-101 were irradiated in a UV photo-reactor and then administered to Daphnia pulex in acute (48 h) exposures comparing toxicities relative to the parent materials. UV-degradation of DNAN had little effect on mortality whereas mortality for UV-degraded NTO and NQ (and associated degradation products) increased by factors of 40.3 and 1240, respectively, making UV-degraded NQ the principle driver of toxicity when IMX-101 is UV-degraded. Toxicity investigations for specific products formed during UV-degradation of NQ, confirmed greater toxicity than the parent NQ for degradation products including guanidine, nitrite, ammonia, nitrosoguanidine, and cyanide. Summation of the individual toxic units for the complete set of individually measured UV-degradation products identified for NQ only accounted for 25% of the overall toxicity measured in the exposures to the UV-degraded NQ product mixture. From these toxic unit calculations, nitrite followed by CN- were the principal degradation products contributing to toxicity. Given the underestimation of toxicity using the sum toxic units for the individually measured UV-degradation products of NQ, we conclude that: (1) other unidentified NQ degradation products contributed principally to toxicity and/or (2) synergistic toxicological interactions occurred among the NQ degradation product mixture that exacerbated toxicity.

Designing Highly Crystalline Multifunctional Multicolor Luminescence Nanosystem for Tracking Breast Cancer Heterogeneity.

Breast tumor heterogeneity is responsible for the death of ~ 40,000 women in 2017 in USA. Triple-negative breast cancers (TNBCs) are very aggressive and it is the only breast cancer subgroup still lacking effective therapeutic. As a result, early stage detection of TNBC is vital and it will have huge significant in the clinics. Driven by the need, here we report the design of highly crystalline antibody-conjugated multifunctional multicolor luminescence nanosystem derived from naturally available popular tropical fruits mango and prune, which have capability to track breast cancer heterogeneity via selective separation and accurate identification of TNBC and HER-2 (+) or ER/PR (+) breast cancer cells selectively and simultaneously. A detailed synthesis and characterization of multifunctional multicolor nanosystems from tropical fruits has been reported. Experimental results show that by changing the fruits, multicolor luminescent carbon dots (LCDs) can be developed and is mainly due to the formation of highly crystalline nano dots with different heavy metal doping and also due to the presence of different types of surface functional groups. Experimental data presented show that multifunctional multicolor nanoprobe can be used for highly selective and simultaneous capturing of targeted TNBCs, HER2(+) or ER(+) breast cancer cells and the capture efficiency can be as high as 98%. Reported data indicate that multicolor fluorescence imaging can be used for mapping hetergenous breast cancer cells simultaneously, and it can distinguish targeted TNBCs from non-targeted HER-2 (+) or ER/PR (+) breast cancer. Our finding suggests excellent possibility of designing multicolor nanosystems from natural fruits for tracking cancer heterogeneity in clinics.

Impact of Nursing Education on Phlebotomy Blood Loss and Hospital-Acquired Anemia: A Quality Improvement Project.

BACKGROUND: Phlebotomy blood loss resulting in hospital-acquired anemia remains a significant problem in the critically ill population. A quality improvement project focused on decreasing phlebotomy blood loss and increasing nursing knowledge regarding blood conservation strategies was undertaken in the intensive care unit of a community hospital. METHODS: The project followed a quasi-experimental design. Data were gathered using electronic chart review and surveys before and after educational sessions. Intensive care unit nurses attended educational sessions focused on increasing knowledge regarding phlebotomy blood loss, hospital-acquired anemia, blood conservation strategies, and utilization of blood conservation devices. RESULTS: The study showed a statistically significant increase in nursing knowledge regarding hospital-acquired anemia, phlebotomy blood loss, and blood conservation device use (P < .001) and a statistically significant change in blood conservation device application practice in the posteducation period when compared with the preeducation period (P = .016). CONCLUSION: The findings of this project support the added value of dedicated blood conservation education to nurses to promote increased knowledge, increased blood conservation device utilization, and decreases in phlebotomy blood loss.

Multifunctional hybrid graphene oxide for circulating tumor cell isolation and analysis.

Even in 21st century, >90% cancer-associated deaths are caused by metastatic disease. Circulating tumor cells (CTCs), which circulate in the blood stream after release from primary tumors, extravasate and form fatal metastases in different organs. Several clinical trials indicate that CTCs can be used as a liquid biopsy of tumors for early diagnosis of cancers. Since CTCs are extremely rare and exhibit heterogeneous biology due to epithelial-mesenchymal transition (EMT), oncologists continue to face enormous challenges in using CTCs as a true "liquid biopsy" for cancer patients. Recent advancements in nanoscience allow us to design nano-architectures with the capability of targeted CTCs isolation and identification. In the current review, we discuss contribution from different groups on the development of graphene oxide based nanoarchitecture for effective isolation and accurate identification of CTCs from whole blood. In the last few years, using zero-dimensional (0D), two dimensional (2D) and three dimensional (3D) multifunctional hybrid graphene oxide (GO), different types of nanoarchitectures have been designed. These nanoarchitectures represent a highly powerful platform for CTC diagnosis. We discuss the major design criteria that have been used to develop hybrid GO nanoarchitectures for selective capture and accurate identification of heterogeneous CTCs from whole blood. At the end, we conclude with the promises, major challenges, and prospect to clinically translate the identification of CTCs using GO based nanotechnology.

Fluorescent, Magnetic Multifunctional Carbon Dots for Selective Separation, Identification, and Eradication of Drug-Resistant Superbugs.

The emergence of drug-resistant superbugs remains a major burden to society. As the mortality rate caused by sepsis due to superbugs is more than 40%, accurate identification of blood infections during the early stage will have a huge significance in the clinical setting. Here, we report the synthesis of red/blue fluorescent carbon dot (CD)-attached magnetic nanoparticle-based multicolor multifunctional CD-based nanosystems, which can be used for selective separation and identification of superbugs from infected blood samples. The reported data show that multifunctional fluorescent magneto-CD nanoparticles are capable of isolating Methicillin-resistant Staphylococcus aureus (MRSA) and Salmonella DT104 superbug from whole blood samples, followed by accurate identification via multicolor fluorescence imaging. As multidrug-resistant (MDR) superbugs are resistant to antibiotics available in the market, this article also reports the design of antimicrobial peptide-conjugated multicolor fluorescent magneto-CDs for effective separation, accurate identification, and complete disinfection of MDR superbugs from infected blood. The reported data demonstrate that by combining pardaxin antimicrobial peptides, magnetic nanoparticles, and multicolor fluorescent CDs into a single system, multifunctional CDs represent a novel material for efficient separation, differentiation, and eradication of superbugs. This material shows great promise for use in clinical settings.

Development of a SERS Probe for Selective Detection of Healthy Prostate and Malignant Prostate Cancer Cells Using ZnII.

Even in the 21st century, prostate cancer remains the second leading cause of cancer-related death for men. Since a normal prostate gland has a high ZnII content and there are huge differences in ZnII content between healthy and malignant prostate cancer cells, mobile zinc can be used as a biomarker for prostate cancer prediction. A highly efficient surface enhanced Raman spectroscopy (SERS) probe using a p-(imidazole)azo)benzenethiol attached gold nanoparticle as a Raman reporter, which has the capability to identify prostate cancer cells based on ZnII sensing, has been designed. A facile synthesis, characterization and evaluation of a ZnII sensing Raman probe are described. Reported data indicate that after binding with ZnII , Raman reporter attached to a gold nanoparticle forms an assembly structure, which allows selective detection of ZnII even at 100 ppt concentration. Theoretical full-wave finite-difference time-domain (FDTD) simulations have been used to understand the enhancement of the SERS signal. The SERS probe is highly promising for in vivo sensing of cancer, where near-IR light can be easily used to avoid tissue autofluorescence and to enhance tissue penetration depth. Reported data show that the SERS probe can distinguish metastatic cancer cells from normal prostate cells very easily with a sensitivity as low as 5 cancer cells mL-1 . The probe can be used as a chemical toolkit for determining mobile ZnII concentrations in biological samples.

Recent progress on the development of anisotropic gold nanoparticles: Design strategies and growth mechanism.

This review summarizes recent advances on design strategies for shape-controlled anisotropic gold nanoparticles. Detailed chemical mechanism has been discussed to understand the anisotropic growth. The effect of various chemical parameters and surface facets for the formation of different shaped anisotropic nanoparticles have been addressed.

Multifunctional Biochar for Highly Efficient Capture, Identification, and Removal of Toxic Metals and Superbugs from Water Samples.

According to the World Health Organization, more than two billion people in our world use drinking water sources which are not free from pathogens and heavy metal contamination. Unsafe drinking water is responsible for the death of several millions in the 21st century. To find facile and cost-effective routes for developing multifunctional materials, which has the capability to resolve many of the challenges associated with drinking water problem, here, we report the novel design of multifunctional fluorescence-magnetic biochar with the capability for highly efficient separation, identification, and removal of pathogenic superbugs and toxic metals from environmental water samples. Details of synthesis and characterization of multifunctional biochar that exhibits very good magnetic properties and emits bright blue light owing to the quantum confinement effect are reported. In our design, biochar, a carbon-rich low-cost byproduct of naturally abundant biomass, which exhibits heterogeneous surface chemistry and strong binding affinity via oxygen-containing group on the surface, has been used to capture pathogens and toxic metals. Biochar dots (BCDs) of an average of 4 nm size with very bright photoluminescence have been developed for the identification of pathogens and toxic metals. In the current design, magnetic nanoparticles have been incorporated with BCDs which allow pathogens and toxic metals to be completely removed from water after separation by an external magnetic field. Reported results show that owing to the formation of strong complex between multifunctional biochar and cobalt(II), multifunctional biochar can be used for the selective capture and removal of Co(II) from environmental samples. Experimental data demonstrate that multifunctional biochar can be used for the highly efficient removal of methicillin-resistant Staphylococcus aureus (MRSA) from environmental samples. Reported results also show that melittin, an antimicrobial peptide-attached multifunctional biochar, has the capability to completely disinfect MRSA superbugs after magnetic separation. A possible mechanism for the selective separation of Co(II), as well as separation and killing of MRSA, has been discussed.

Two-Photon Fluorescent Molybdenum Disulfide Dots for Targeted Prostate Cancer Imaging in the Biological II Window.

Molybdenum disulfide (MoS2) quantum dots (QDs) derived from this two-dimensional (2D) transition metal dichalcogenide are emerging zero-dimensional materials that possess very good optical properties. Bioimaging using light in the biological II window (950-1350 nm) is a next-generation approach that will allow clinicians to achieve deeper tissue imaging with better image contrast and reduced phototoxicity and photobleaching. This article reports the development of a water-soluble, zero-dimensional antibody-conjugated transition metal dichalcogenide MoS2 QD-based two-photon luminescence (TPL) probe for the targeted bioimaging of cancer cells in the biological II window. The data indicates that MoS2 QDs exhibit an extremely high two-photon absorption cross-section (σ = 58960 GM) and two-photon brightness (4.7 × 103 GM) because of the quantum confinement and edge effects. Experimental data show that anti-PSMA antibody-attached MoS2 QDs can be used for selective two-photon imaging of live prostate cancer cells using 1064 nm light because of the high two-photon brightness, very good photostability, and very good biocompatibility of these MoS2 QDs. The data demonstrate that the bioconjugated MoS2 QDs can distinguish targeted and nontargeted cells. This study illuminates the high two-photon brightness mechanism of MoS2 QDs and provides a zero-dimensional transition metal dichalcogenide-based selective TPL agent for high-efficiency live cell imaging.

A bio-conjugated chitosan wrapped CNT based 3D nanoporous architecture for separation and inactivation of Rotavirus and Shigella waterborne pathogens.

The United Nations (UN) estimates that more than one billion people in this world do not have access to safe drinking water due to microbial hazards and it kills more than 7.6 million children every year via waterborne diseases. Driven by the need for the removal and inactivation of waterborne pathogens in drinking water, we report the chemical design and details of microscopic characterization of a bio-conjugated chitosan attached carbon nanotube based three dimensional (3D) nanoporous architecture, which has the capability for effective separation and complete disinfection of waterborne pathogens from environmental water samples. In the reported design, chitosan, a biodegradable antimicrobial polysaccharide with an architecture-forming ability has been used for the formation of 3D pores as channels for water passage, as well as to increase the permeability on the inner and outer architectures for killing Rotavirus and Shigella waterborne pathogens. On the other hand, due to their large surface area, CNTs have been wrapped by chitosan to enhance the adsorption capability of the architecture for the separation and removal of pathogens from water. The reported data show that the anti-Rotavirus VP7 antibody and LL-37 antimicrobial peptide conjugated chitosan-CNT architecture can be used for efficient separation, identification and 100% eradication of Rotavirus and Shigella waterborne pathogens from water samples of different sources. A detailed mechanism for the separation and inactivation of waterborne pathogens using the bio-conjugated chitosan based 3D architecture has been discussed using microscopic and spectroscopic studies. Reported experimental data demonstrate that the multifunctional bio-conjugated 3D architecture has good potential for use in waterborne pathogen separation and inactivation technology.

Nanoarchitecture Based SERS for Biomolecular Fingerprinting and Label-Free Disease Markers Diagnosis.

Surface-enhanced Raman spectroscopy (SERS) fingerprinting is highly promising for identifying disease markers from complex mixtures of clinical sample, which has the capability to take medical diagnoses to the next level. Although vibrational frequency in Raman spectra is unique for each biomolecule, which can be used as fingerprint identification, it has not been considered to be used routinely for biosensing due to the fact that the Raman signal is very weak. Contemporary SERS has been demonstrated to be an excellent analytical tool for practical label-free sensing applications due its ability to enhance Raman signals by factors of up to 108-1014 orders of magnitude. Although SERS was discovered more than 40 years ago, its applications are still rare outside the spectroscopy community and it is mainly due to the fact that how to control, manipulate and amplify light on the "hot spots" near the metal surface is in the infancy stage. In this Account, we describe our contribution to develop nanoachitecture based highly reproducible and ultrasensitive detection capability SERS platform via low-cost synthetic routes. Using one-dimensional (1D) carbon nanotube (CNT), two-dimensional (2D) graphene oxide (GO), and zero-dimensional (0D) plasmonic nanoparticle, 0D to 3D SERS substrates have been designed, which represent highly powerful platform for biological diagnosis. We discuss the major design criteria we have used to develop robust SERS substrate to possess high density "hot spots" with very good reproducibility. SERS enhancement factor for 3D SERS substrate is about 5 orders of magnitude higher than only plasmonic nanoparticle and more than 9 orders of magnitude higher than 2D GO. Theoretical finite-difference time-domain (FDTD) stimulation data show that the electric field enhancement |E|2 can be more than 2 orders of magnitude in "hot spots", which suggests that SERS enhancement factors can be greater than 104 due to the formation of high density "hot spots" in 3D substrate. Next, we discuss the utilization of nanoachitecture based SERS substrate for ultrasensitive and selective diagnosis of infectious disease organisms such as drug resistance bacteria and mosquito-borne flavi-viruses that cause significant health problems worldwide. SERS based "whole-organism fingerprints" has been used to identify infectious disease organisms even when they are so closely related that they are difficult to distinguish. The detection capability can be as low as 10 CFU/mL for methicillin-resistant Staphylococcus aureus (MRSA) and 10 PFU/mL for Dengue virus (DENV) and West Nile virus (WNV). After that, we introduce exciting research findings by our group on the applications of nanoachitecture based SERS substrate for the capture and fingerprint detection of rotavirus from water and Alzheimer's disease biomarkers from whole blood sample. The SERS detection limit for ß-amyloid (Aß proteins) and tau protein using 3D SERS platform is several orders of magnitude higher than the currently used technology in clinics. Finally, we highlight the promises, major challenges and prospect of nanoachitecture based SERS in biomedical diagnosis field.

Genomic Characterization of Metformin Hepatic Response.

Metformin is used as a first-line therapy for type 2 diabetes (T2D) and prescribed for numerous other diseases. However, its mechanism of action in the liver has yet to be characterized in a systematic manner. To comprehensively identify genes and regulatory elements associated with metformin treatment, we carried out RNA-seq and ChIP-seq (H3K27ac, H3K27me3) on primary human hepatocytes from the same donor treated with vehicle control, metformin or metformin and compound C, an AMP-activated protein kinase (AMPK) inhibitor (allowing to identify AMPK-independent pathways). We identified thousands of metformin responsive AMPK-dependent and AMPK-independent differentially expressed genes and regulatory elements. We functionally validated several elements for metformin-induced promoter and enhancer activity. These include an enhancer in an ataxia telangiectasia mutated (ATM) intron that has SNPs in linkage disequilibrium with a metformin treatment response GWAS lead SNP (rs11212617) that showed increased enhancer activity for the associated haplotype. Expression quantitative trait locus (eQTL) liver analysis and CRISPR activation suggest that this enhancer could be regulating ATM, which has a known role in AMPK activation, and potentially also EXPH5 and DDX10, its neighboring genes. Using ChIP-seq and siRNA knockdown, we further show that activating transcription factor 3 (ATF3), our top metformin upregulated AMPK-dependent gene, could have an important role in gluconeogenesis repression. Our findings provide a genome-wide representation of metformin hepatic response, highlight important sequences that could be associated with interindividual variability in glycemic response to metformin and identify novel T2D treatment candidates.

Three-dimensional (3D) plasmonic hot spots for label-free sensing and effective photothermal killing of multiple drug resistant superbugs.

Drug resistant superbug infection is one of the foremost threats to human health. Plasmonic nanoparticles can be used for ultrasensitive bio-imaging and photothermal killing by amplification of electromagnetic fields at nanoscale "hot spots". One of the main challenges to plasmonic imaging and photothermal killing is design of a plasmonic substrate with a large number of "hot spots". Driven by this need, this article reports design of a three-dimensional (3D) plasmonic "hot spot"-based substrate using gold nanoparticle attached hybrid graphene oxide (GO), free from the traditional 2D limitations. Experimental results show that the 3D substrate has capability for highly sensitive label-free sensing and generates high photothermal heat. Reported data using p-aminothiophenol conjugated 3D substrate show that the surface enhanced Raman spectroscopy (SERS) enhancement factor for the 3D "hot spot"-based substrate is more than two orders of magnitude greater than that for the two-dimensional (2D) substrate and five orders of magnitude greater than that for the zero-dimensional (0D) p-aminothiophenol conjugated gold nanoparticle. 3D-Finite-Difference Time-Domain (3D-FDTD) simulation calculations indicate that the SERS enhancement factor can be greater than 104 because of the bent assembly structure in the 3D substrate. Results demonstrate that the 3D-substrate-based SERS can be used for fingerprint identification of several multi-drug resistant superbugs with detection limits of 5 colony forming units per mL. Experimental data show that 785 nm near infrared (NIR) light generates around two times more photothermal heat for the 3D substrate with respect to the 2D substrate, and allows rapid and effective killing of 100% of the multi-drug resistant superbugs within 5 minutes.