The learning curve for minimally invasive Achilles repair using the "lumbar puncture needle and oval forceps" technique.

INTRODUCTION: An acute Achilles tendon rupture represents a common tendon injury, and its operative methods have been developed over the years. This study aimed to quantify the learning curve for the minimally invasive acute Achilles tendon rupture repair. METHODS: From May 2020 to June 2022, sixty-seven patient cases who received minimally invasive tendon repair were reviewed. Baseline data and operative details were collected. The cumulative summation (CUSUM) control chart was used for the learning curve analyses. Achilles tendon rupture score (ATRS), American Orthopedic Foot and Ankle Society (AOFAS) ankle/hindfoot score, and visual analog scale (VAS) at 3/6/9/12 months were calculated to assess the clinical outcomes. RESULTS: Thirty-six cases underwent at least a year of follow up and were enrolled in this study. The gender ratio and average age were 80.5% and 32.5 years. The linear equation fitted well (R2 = 0.95), and CUSUM for operative time peaked in the 12th case, which was divided into the learning phase (n = 12) and master phase (n = 24). No significant difference was detected between the two groups in clinical variables, except for the operative time (71.1 ± 13.2 min vs 45.8 ± 7.2 min, p = 0.004). Moreover, we detected one case with a suture reaction and treated it properly. CONCLUSION: Minimally invasive Achilles repair provides an opportunity for early rehabilitation. Notably, the learning curve showed that the "lumbar puncture needle and oval forceps" technique was accessible to surgeons.

Molecular imaging of biological systems with a clickable dye in the broad 800- to 1,700-nm near-infrared window.

Fluorescence imaging multiplicity of biological systems is an area of intense focus, currently limited to fluorescence channels in the visible and first near-infrared (NIR-I; ∼700-900 nm) spectral regions. The development of conjugatable fluorophores with longer wavelength emission is highly desired to afford more targeting channels, reduce background autofluorescence, and achieve deeper tissue imaging depths. We have developed NIR-II (1,000-1,700 nm) molecular imaging agents with a bright NIR-II fluorophore through high-efficiency click chemistry to specific molecular antibodies. Relying on buoyant density differences during density gradient ultracentrifugation separations, highly pure NIR-II fluorophore-antibody conjugates emitting ∼1,100 nm were obtained for use as molecular-specific NIR-II probes. This facilitated 3D staining of ∼170-µm histological brain tissues sections on a home-built confocal microscope, demonstrating multicolor molecular imaging across both the NIR-I and NIR-II windows (800-1,700 nm).

IL-17A promotes cell migration and invasion of glioblastoma cells via activation of PI3K/AKT signalling pathway.

Glioblastomas (GBMs) are the most common of both benign and malignant primary brain tumours, in which the inflammatory and immunologic abnormalities are involved. Interleukin-17A (IL-17A) plays an important role in various inflammatory diseases and cancers. Several recent studies revealed that the expression of IL-17A was overexpressed in human GBMs tissue. However, the accurate role of IL-17A in GBMs remains unclear. In this study, we aimed to explore the effect of IL-17A on cell migration and invasion of GBMs and the mechanism by which the effects occurred. We found that exogenous IL-17A promoted significantly cell migration and invasion abilities in two GBMs cell lines (U87MG and U251) in a time-dependent manner. In addition, the protein expressions of PI3K, Akt and MMP-2/9 were increased in the GBMs cells challenged by IL-17A. Furthermore, a tight junction protein ZO-1 was down-regulated but Twist and Bmi1 were up-regulated. Treatment with a PI3K inhibitor (LY294002) significantly reduced the abilities of both migration and invasion in U87MG and U251 cells. LY294002 treatment also attenuated the IL-17A causing increases of protein levels of PI3K, AKT, MMP-2/9, Twist and the decreases of protein level of ZO-1 in the U87MG and U251 cells. Taken together, we concluded that IL-17A promotes the GBM cells migration and invasion via PI3K/AKT signalling pathway. IL-17A and its related signalling pathways may be potential therapeutic targets for GBM.

Direct Evidence for Coupled Surface and Concentration Quenching Dynamics in Lanthanide-Doped Nanocrystals.

Luminescence quenching at high dopant concentrations generally limits the dopant concentration to less than 1-5 mol% in lanthanide-doped materials, and this remains a major obstacle in designing materials with enhanced efficiency/brightness. In this work, we provide direct evidence that the major quenching process at high dopant concentrations is the energy migration to the surface (i.e., surface quenching) as opposed to the common misconception of cross-relaxation between dopant ions. We show that after an inert epitaxial shell growth, erbium (Er3+) concentrations as high as 100 mol% in NaY(Er)F4/NaLuF4 core/shell nanocrystals enhance the emission intensity of both upconversion and downshifted luminescence across different excitation wavelengths (980, 800, and 658 nm), with negligible concentration quenching effects. Our results highlight the strong coupling of concentration and surface quenching effects in colloidal lanthanide-doped nanocrystals, and that inert epitaxial shell growth can overcome concentration quenching. These fundamental insights into the photophysical processes in heavily doped nanocrystals will give rise to enhanced properties not previously thought possible with compositions optimized in bulk.

A small-molecule dye for NIR-II imaging.

Fluorescent imaging of biological systems in the second near-infrared window (NIR-II) can probe tissue at centimetre depths and achieve micrometre-scale resolution at depths of millimetres. Unfortunately, all current NIR-II fluorophores are excreted slowly and are largely retained within the reticuloendothelial system, making clinical translation nearly impossible. Here, we report a rapidly excreted NIR-II fluorophore (∼90% excreted through the kidneys within 24 h) based on a synthetic 970-Da organic molecule (CH1055). The fluorophore outperformed indocyanine green (ICG)-a clinically approved NIR-I dye-in resolving mouse lymphatic vasculature and sentinel lymphatic mapping near a tumour. High levels of uptake of PEGylated-CH1055 dye were observed in brain tumours in mice, suggesting that the dye was detected at a depth of ∼4 mm. The CH1055 dye also allowed targeted molecular imaging of tumours in vivo when conjugated with anti-EGFR Affibody. Moreover, a superior tumour-to-background signal ratio allowed precise image-guided tumour-removal surgery.

Single Chirality (6,4) Single-Walled Carbon Nanotubes for Fluorescence Imaging with Silicon Detectors.

Postsynthetic single-walled carbon nanotube (SWCNT) sorting methods such as density gradient ultracentrifugation, gel chromatography, and electrophoresis have all been inspired by established biochemistry separation techniques designed to separate subcellular components. Biochemistry separation techniques have been refined to the degree that parameters such as pH, salt concentration, and temperature are necessary for a successful separation, yet these conditions are only now being applied to SWCNT separation methodologies. Slight changes in pH produce radically different behaviors of SWCNTs inside a density gradient, allowing for the facile separation of ultrahigh purity (6,4) SWCNTs from as-synthesized carbon nanotubes. The (6,4) SWCNTs are novel fluorophores emitting below ≈900 nm and can be easily detected with conventional silicon-based charge-coupled device detectors without the need for specialized InGaAs cameras. The (6,4) SWCNTs are used to demonstrate their potential as a clinically relevant NIR-I fluorescence stain for the immunohistochemical staining of cells and cancer tissue sections displaying high endothelial growth factor receptor levels.

Fluorescence Imaging In Vivo at Wavelengths beyond 1500†nm.

Compared to imaging in the visible and near-infrared regions below 900 nm, imaging in the second near-infrared window (NIR-II, 1000-1700 nm) is a promising method for deep-tissue high-resolution optical imaging in vivo mainly owing to the reduced scattering of photons traversing through biological tissues. Herein, semiconducting single-walled carbon nanotubes with large diameters were used for in vivo fluorescence imaging in the long-wavelength NIR region (1500-1700 nm, NIR-IIb). With this imaging agent, 3-4 µm wide capillary blood vessels at a depth of about 3 mm could be resolved. Meanwhile, the blood-flow speeds in multiple individual vessels could be mapped simultaneously. Furthermore, NIR-IIb tumor imaging of a live mouse was explored. NIR-IIb imaging can be generalized to a wide range of fluorophores emitting at up to 1700 nm for high-performance in vivo optical imaging.

A new method regulates bone fracture tissue exosome lncRNA-mRNA to promote mesenchymal stem cell proliferation and migration.

Post-injury adaptation (PIA) is a simple and convenient method to promote bone healing, but its mechanism is unclear. This study was to discuss the role of fracture site tissue exosomes lncRNAs-mRNAs networks on PIA promoting bone mesenchymal stem cells (BMSCs) proliferation and migration. Firstly, the effects of PIA accelerating BMSCs proliferation and migration were confirmed by rat fracture model and bone fracture environment in vitro. Besides, the fracture site tissue exosomes were isolated and authenticated. Then the tissue exosomes were the key factor in PIA promoting BMSCs proliferation and migration authenticated by in vitro and in vivo experiments. The high throughput sequencing and RT-PCR were used to analyze the tissue exosomes lncRNAs-mRNAs networks. It was found that PIA treatment upregulated 118 lncRNAs, 295 mRNAs, and downregulated 111 lncRNAs, 2706 mRNAs in tissue exosomes. A total 12,211 genes were the target genes. Akt1, Actb and Uba52 were the hub mRNAs in tissue exosomes. In additions, tissue-derived exosomes of PIA treated rats upregulated 49 genes, 3 lncRNAs and downregulated 28 genes, 1 lncRNA in BMSCs. Kif11 was the hub gene. Overall, PIA promoted BMSCs proliferation and migration in the early stage of fracture healing, which was closely related to the fracture site tissue exosomes. Akt1, Actb and Uba52 were the hub mRNAs in the exosomes. Besides, Kif11 might be the key gene in BMSC regulated by tissue-derived exosomes of PIA treated rats.

Comparison of operatively and nonoperatively treated isolated mason type II radial head fractures: a systematic review and meta-analysis.

BACKGROUND: Radial head fractures are the most common bony injury of the elbow in adults. The current literature does not agree on whether isolated stable type II radial head fractures should be treated operatively or nonoperatively. This review aims to determine the preferred treatment for Mason type II radial head fractures and compare the outcomes of conservative and surgical treatment. METHODS: Our study used PRISMA guidelines and conducted a thorough search of multiple electronic databases, including PubMed, Cochrane, Embase, Web of Science, CNKI, and Wanfang databases, initially identifying 545 relevant publications on surgical and conservative treatment of Mason type II radial head fractures. The final search date for this study is July 7, 2024.Through a comprehensive meta-analysis, we evaluated several outcomes, including functional scores (DASH, OES, and MEPS scores), clinical outcomes (elbow flexion, elbow extension deficit, elbow pronation, and elbow supination), and complication rate (total complications and elbow pain). The mean difference (MD) was compared for continuous outcomes, and the odds ratios (ORs) were compared for categorical outcomes. RESULT: A total of 271 patients from 4 studies met the inclusion criteria. Among them, 142 patients received surgical treatment and 129 patients received non-surgical treatment. The study found no statistically significant differences between surgical and non-surgical treatments in DASH, OES, MEPS, elbow flexion, elbow extension impairment, and elbow pain. Compared with surgical treatment, non-surgical treatment was associated with greater elbow pronation (OR = -3.10, 95% CI = [-4.96, -1.25], P = 0.55, I2 = 0%) and a lower complication rate (OR = 5.54, 95% CI = [1.79, 17.14], P = 0.42, I2 = 0%). CONCLUSION: Based on the current evidence, conservative management of isolated Mason II radial head fractures yields favorable therapeutic outcomes with a low incidence of complications.

Formaldehyde-free and durable phosphorus-containing cotton flame retardant with -N=P-(N)3- and reactive ammonium phosphoric acid groups.

A flame retardant (FR) hexachlorocyclotriphosphazene diethylenetriamine ammonium phosphoric acid (HDAPA) was synthesized. Vertical flammability test and limiting oxygen index (LOI) results showed that cotton samples finished with HDAPA solutions (15 % and 20 %) could pass vertical flame retardancy test, and LOIs reached 30.1 % and 35.4 % even after 50 laundering cycles according to AATCC 61-2013 3A washing standard (3A), performing flame retardancy and washing durability. Meanwhile, Fourier transform infrared and X-ray photoelectron spectroscopy analyses suggested that HDAPA was grafted on cotton fibers through -P(=O)-O-C covalent bond. Total heat release (1.98 MJ/m2) and char residue (16.2 %) of HDAPA treated cotton were much lower than those (4.26 MJ/m2, 3.2 %) of untreated cotton. Thermogravimetry results showed HDAPA changed thermal decomposition pathway of cotton fabric, which was further supported by thermogravimetric-Fourier infrared spectrometer results, revealing HDAPA performed a condensed phase flame retardancy mechanism. Scanning electron microscopy implied HDAPA entered amorphous region of cotton fibers to react with cellulose. Mechanical properties of HDAPA treated cotton decreased a little. Although the synthesis process used formaldehyde but no free formaldehyde released. In consequence, the aforementioned results indicated that the introduction of -N=P-(N)3- and -P(=O)(O-NH4+)2 groups to FR was an viable method to improve flame retardancy and durability.

A cationic, durable, P/N-containing starch-based flame retardant for cotton fabrics.

A cationic, durable flame retardant for cotton fabrics, 6-(2-(dimethoxy phosphoryl)-2-(trimethyl ammonium)) methoxy-2-methoxy-polysaccharide ammonium phosphate (DTPAP), was synthesized. Its structure was verified by NMR and FTIR spectroscopy. According to the FTIR spectra and X-ray photoelectron spectroscopy (XPS), DTPAP formed P(=O)-O-C bonds with cellulose molecules and firmly grafted to cotton fabrics, giving the fabric a high durability. DTPAP-25-treated fabrics passed the vertical flame test (VFT), and the limiting oxygen index (LOI) was 43.9 %. After 50 laundering cycles (LCs), the DTPAP-25-treated fabrics had an LOI of 29.9 %, passed the VFT, and retained their flame retardancy. EDS data showed that, compared with engrafted cationic ammonium phosphate flame retardants, the DTPAP-treated fabrics contained fewer metal ions. Cone calorimetry data showed that DTPAP-25-treated fabrics did not display concentrated heat release. The results suggested that DTPAP exhibited a condensed-phase flame retardant mechanism, and the introduction of cations into the ammonium phosphate flame retardant reduced ion exchange, which improved the durability.

Self-assembly of semiconducting single-walled carbon nanotubes into dense, aligned rafts.

Highly pure semiconducting single-walled carbon nanotubes (SWNTs) are separated from bulk materials and self-assembled into densely aligned rafts. Microscopy and spectroscopy reveals ∼100 SWNTs per micrometer within the rafts. Short channel field-effect transistors (FETs) from tens of purely semiconducting SWNTs within a submicrometer channel width achieve unprecedented on-currents (up to 121 µA) with high on/off ratios. The results demonstrate densely aligned semiconducting SWNTs for high-performance nanoelectronics.

Biological imaging using nanoparticles of small organic molecules with fluorescence emission at wavelengths longer than 1000 nm.

Embedded in a polymer: A hydrophobic organic molecule that fluoresces in the near-infrared II (NIR-II) region was made water-soluble and biocompatible by its embedment in a polymer nanoparticle, which was then coated with hydrophilic poly(ethylene glycol) chains. The resulting nanoparticles exhibit bright fluorescence in the NIR-II window and high photostability in aqueous media and were used for in vivo imaging in mice.

Efficiency evaluation and nonlinear multi-objective optimization of forestry industry transformation in the Heilongjiang state-owned forest region.

With the deepening of the concept of sustainable development of the whole society, protecting forest resources has become a crucial task of the current society. The present forestry industrial structure of Heilongjiang state-owned forest areas has undergone significant changes, and the transformation of the forestry industry has become increasingly prominent. How to deepen the forestry industry transformation and improve its efficiency has become an important research direction in forest areas. This work first analyzes the data envelopment method, and further designs the evaluation method of forestry transformation efficiency in forest areas. Then, the evaluation index system of forestry industry transformation efficiency in Heilongjiang state-owned forest areas is built. The relevant nonlinear multi-objective optimization (MOO) constraints are designed. Relevant data are quoted to evaluate the efficiency of the forestry industry transformation in the Heilongjiang state-owned forest areas. The results show that: (1) During 2015-2021, the average value of the scale, technical, and comprehensive production efficiencies of Heilongjiang state-owned forest areas were 0.765, 0.53, and 0.399, all of which were less than 1. And they were in a relatively ineffective state. (2) The overall industrial transformation of state-owned forest areas was optimistic. The technical efficiency decreased slightly in 2017, while the pure technical efficiency was greater than 1 in 2016 and 2018. The efficiency value increased to the peak by the end of 2021. (3) In the transformation of the forestry industry in state-owned forest areas, the influence of the industrial economy and resource protection subsystems was the first and backward, and the contribution of the social development subsystem was in the middle. (4) In the MOO problem, the forest area should be planned according to the proportion of public welfare, multi-functional, and commercial forests: 35.2%, 38.8%, and 26%, respectively. This work provides an essential reference for protecting forest resources and contributes to the transformation and development of the social forestry industry.

Long Non-Coding RNAs Within Macrophage-Derived Exosomes Promote BMSC Osteogenesis in a Bone Fracture Rat Model.

Purpose: To investigate the effect of macrophage exosomal long non-coding (lnc)RNAs on bone mesenchymal stem cell (BMSC) osteogenesis and the associated mechanism. Methods: Rat BMSCs and spleen macrophages were co-cultured with serum derived from the fracture microenvironment of rat tibia. BMSC osteogenesis was evaluated using Alizarin red staining and the expression of BMP-2, RUNX2, OPN, and OC mRNA. BMSC osteogenesis was evaluated after co-culture with macrophages stimulated using hypoxic conditions or colony-stimulating factor (CSF). The uptake of macrophage-derived exosomes by BMSCs was evaluated using the exosome uptake assay. High-throughput sequencing and bioinformatics analyses were performed to identify key lncRNAs in the macrophage exosomes. The effect of lncRNA expression levels on BMSC osteogenesis was also assessed using a lncRNA overexpression plasmid and siRNA technology. M1 and M2 macrophages were distinguished using flow cytometry and the key exosomal lncRNA was detected by in situ hybridization. Results: In the fracture microenvironment, macrophages (stimulated using either hypoxia or CSF) significantly increased the osteogenic ability of BMSCs. We showed that BMSCs assimilated macrophage-derived vesicles and that the inhibition of exosomal secretion significantly attenuated the macrophage-mediated induction of BMSC osteogenesis. The hypoxia condition led to the up-regulation of 310 lncRNAs and the down-regulation of 575 lncRNAs in macrophage exosomes, while CSF stimulation caused the up-regulation of 557 lncRNAs and the down-regulation of 407 lncRNAs. In total, 108 lncRNAs were co-up-regulated and 326 lncRNAs were co-down-regulated under both conditions. We eventually identified LOC103691165 as a key lncRNA that promoted BMSC osteogenesis and was expressed at similar levels in both M1 and M2 macrophages. Conclusion: In the fracture microenvironment, M1 and M2 macrophages promoted BMSC osteogenesis by secreting exosomes containing LOC103691165.

The Role of Combined Inflammatory Biomarkers in the Diagnosis of High- and Low-Virulence FRI Among High-Risk Lower Extremity Fractures.

Objective: The aim of this study is to evaluate the diagnostic accuracy of infection-related biomarkers in high-risk lower limb injury patients with fracture-related infection (FRI) caused by high-/low-virulence microorganisms. Methods: This study was a retrospective analysis of patients with high-risk lower extremity fractures (including tibial plateau, calcaneus, and Pilon fractures) who underwent open reduction internal fixation (ORIF) surgery from January 2017 to February 2022. Peripheral blood samples were collected within 24 hours of admission, and the following information was evaluated: gender, age, BMI, smoking, comorbidities, injury information, surgical details, values for serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), as well as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR). Results: A total of 576 patients receiving lower extremity fracture surgery were included in this study. Fifty-one patients (8.85%) were identified as FRI, and 28 (54.9%) of these 51 cases were further classified as high-virulence group. The median levels of CRP, ESR, NLR, and MLR were significantly higher in the FRI group than in the non-FRI group (p < 0.01). Similarly, the marginally significantly higher levels of CRP and NLR presented in the high-virulence group, compared to the low-virulence group (p < 0.1). The AUC areas of CRP, NLR, and CRP+NLR were 0.826, 0.650, and 0.873, respectively. We calculated the optimal cut-off points for CRP+NLR as diagnostic markers of high-virulent infection was 0.377. Conclusion: This study showed the incidence of FRI in high-risk lower extremity fractures was 8.9%, and identified preoperative serum biomarkers, including CRP, ESR, NLR, and PLR, as useful tools for assisting in the diagnosis of infection. Additionally, the combination of CRP with NLR played a discriminating clinical role in postoperative infections caused by different virulence. Level of Evidence: Clinical study.

Comparative Analysis of Eccentric Glenosphere in Reverse Total Shoulder Arthroplasty: A Computer Simulation Study.

Objective: The aim was to evaluate the effects of different glenosphere eccentricities on impingement, range of motion (ROM), and muscle length during standard activities in reverse total shoulder arthroplasty (RSA). Methods: In this study, we utilized computational modeling techniques to create native shoulder and shoulder models undergoing RSA and simulate shoulder movements in all abduction-adduction, flexion-extension, and rotation. We tested a total of 36 different glenosphere configurations, which included three different inferior tilts (0°, +10°, +20°) and two different lateral offsets (0 mm and +4 mm), as well as six different glenosphere eccentricities (concentricity, inferior, posterior, anterior, anteroinferior, and posteroinferior). We evaluated the maximum impingement-free ROM, impingement sites, and muscle lengths. Results: All glenosphere configurations exceeded 50% of native shoulder ROM in three planes and total global ROM. In abduction-adduction, there was no significant difference among the different glenosphere eccentricities (p > 0.05). In flexion-extension, the posteroinferior eccentricity had the maximum ROM among the different eccentricities, but no significant difference among the different glenosphere eccentricities (p > 0.05). In rotation, there was a significant difference overall, and anteroinferior eccentricity had a significant advantage over concentricity (p < 0.05). In total global ROM, anteroinferior eccentricity had a significant advantage over concentricity when lateral offset was 0 mm (p < 0.05). In all models of glenosphere eccentricities, only the elongation of the infraspinatus muscle was statistically significant (p < 0.05). Conclusion: Glenosphere eccentricity significantly influenced rotation, total global ROM, and the length of the subscapularis muscle. Among them, anteroinferior offset achieved the maximum ROM in abduction-adduction, rotation, and total global activities. Both anteroinferior and inferior glenoid eccentricity showed significant advantages over the concentricity in rotation and total global ROM. Level of Evidence: Basic Science Study; Computer Modeling.

Intrawound application of vancomycin reduces the proportion of fracture-related infections in high-risk tibial plateau fractures.

INTRODUCTION: Despite the improvements in surgical techniques and the use of prophylactic intravenous antibiotics, the fracture-related infection (FRI) incidence after high-risk tibial plateau fractures remains high. This study aimed to evaluate the clinical effect of the intrawound application of vancomycin on the FRI after high-risk tibial plateau fracture surgery. METHODS: A total of 243 patients who underwent high-risk tibial plateau fracture surgery from May 2013 to June 2021 were retrospectively reviewed. Of these, 233 cases were enrolled. Considering the preoperative patient condition, surgeons applied vancomycin powder directly into the surgical site before wound closure in 105 cases (intrawound application of vancomycin powder with preoperative intravenous cephalosporin). The remaining 128 cases served as the control group (preoperative intravenous cephalosporin alone). Clinical data and surgical details were recorded. The Cox proportional hazards regression analysis was used to assess risk factors for FRI. The Kaplan-Meier method and the log rank test illustrated the infection status of patients based on the application of intrawound vancomycin. The primary outcome was an FRI within one year. Secondary outcomes included bacterial culture and vancomycin-related complications. RESULTS: Our study demonstrated a significant difference in the incidence of FRI between the vancomycin group and the control group (3.8% versus 10.9%; p=0.041). Multivariable Cox regression showed the intrawound application of vancomycin powder decreased the rate of FRI. There were no complications related to intrawound vancomycin observed during follow-up. The presence of Gram-positive FRI was higher in the control group compared with the vancomycin group. CONCLUSIONS: Intrawound application of vancomycin was associated with a significant lower rate of FRI after high-risk tibial plateau fracture surgery compared to the control group.

Pharmacokinetic/Pharmacodynamic Evaluation of Aztreonam/Amoxicillin/Clavulanate Combination against New Delhi Metallo-ß-Lactamase and Serine-ß-Lactamase Co-Producing Escherichia coli and Klebsiella pneumoniae.

This study aimed to examine specific niches and usage for the aztreonam/amoxicillin/clavulanate combination and to use population pharmacokinetic simulations of clinical dosing regimens to predict the impact of this combination on restricting mutant selection. The in vitro susceptibility of 19 New-Delhi metallo-ß-lactamase (NDM)-producing clinical isolates to amoxicillin/clavulanate and aztreonam alone and in co-administration was determined based on the minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC). The fractions of a 24-h duration that the free drug concentration was within the mutant selection window (fTMSW) and above the MPC (fT>MPC) in both plasma and epithelial lining fluid were determined from simulations of 10,000 subject profiles based on regimens by renal function categories. This combination reduced the MIC of aztreonam and amoxicillin/clavulanate to values below their clinical breakpoint in 7/9 K. pneumoniae and 8/9 E. coli, depending on the ß-lactamase genes detected in the isolate. In the majority of the tested isolates, the combination resulted in fT>MPC > 90% and fTMSW < 10% for both aztreonam and amoxicillin/clavulanate. Clinical dosing regimens of aztreonam and amoxicillin/clavulanate were sufficient to provide mutant restriction coverage for MPC and MIC ≤ 4 mg/L. This combination has limited coverage against NDM- and extended-spectrum ß-lactamase co-producing E. coli and K. pneumoniae and is not effective against isolates carrying plasmid-mediated AmpC and KPC-2. This study offers a potential scope and limitations as to where the aztreonam/amoxicillin/clavulanate combination may succeed or fail.

Chirality enriched (12,1) and (11,3) single-walled carbon nanotubes for biological imaging.

The intrinsic band gap photoluminescence of semiconducting single-walled carbon nanotubes (SWNTs) makes them promising biological imaging probes in the second near-infrared (NIR-II, 1.0-1.4 µm) window. Thus far, SWNTs used for biological applications have been a complex mixture of metallic and semiconducting species with random chiralities, preventing simultaneous resonant excitation of all semiconducting nanotubes and emission at a single well-defined wavelength. Here, we developed a simple gel filtration method to enrich semiconducting (12,1) and (11,3) SWNTs with identical resonance absorption at ~808 nm and emission near ~1200 nm. The chirality sorted SWNTs showed ~5-fold higher photoluminescence intensity under resonant excitation of 808 nm than unsorted SWNTs on a per-mass basis. Real-time in vivo video imaging of whole mouse body and tumor vessels was achieved using a ~6-fold lower injected dose of (12,1) and (11,3) SWNTs (~3 µg per mouse or ~0.16 mg/kg of body weight vs 1.0 mg/kg for unsorted SWNTs) than a previous heterogeneous mixture, demonstrating the first resonantly excited and chirality separated SWNTs for biological imaging.