Crown ether decorated silicon photonics for safeguarding against lead poisoning.

Lead (Pb2+) toxification is a concerning, unaddressed global public health crisis that leads to 1 million deaths annually. Yet, public policies to address this issue have fallen short. This work harnesses the unique abilities of crown ethers, which selectively bind to specific ions. This study demonstrates the synergistic integration of highly-scalable silicon photonics, with crown ether amine conjugation via Fischer esterification in an environmentally-friendly fashion. This realizes an integrated photonic platform that enables the in-operando, highly-selective and quantitative detection of various ions. The development dispels the existing notion that Fischer esterification is restricted to organic compounds, facilitating the subsequent amine conjugation for various crown ethers. The presented platform is specifically engineered for selective Pb2+ detection, demonstrating a large dynamic detection range, and applicability to field samples. The compatibility of this platform with cost-effective manufacturing indicates the potential for pervasive implementation of the integrated photonic sensor technology to safeguard against societal Pb2+ poisoning.

Carpal Joint Malalignment With Distal Radius Malunion and Factors in Correction After Distal Radius Osteotomy.

Purpose: There is a paucity of data regarding recommendations on when to correct for distal radius malunions and if the initial severity of the radiographic outcomes is correlated with the ability to correct to baseline. We evaluated the effects of distal radius corrective osteotomy on preoperative carpal joint malalignment resulting from distal radius malunions, correlated injury severity and osteotomy timing to radiographic outcomes, and developed a straightforward classification system for predicting radiocarpal and midcarpal maladaptive patterns. Methods: A retrospective review included 26 patients (27 wrists) who reported initial closed treatment for a distal radius fracture and who subsequently underwent a corrective osteotomy for malunion. Data included patient demographics, range of motion, preoperative fracture deformity, fracture deformity correction, and preoperative and postoperative radiographic measurements of the radiocarpal and midcarpal alignment patterns. Results: Of 27 dorsally angulated malunions, 16 were classified as type 1 midcarpal adaptation and 11 as type 2 radiocarpal adaptation. The midcarpal group showed significant improvements in distal radius and carpal alignment parameters after surgery, except for the ulnar variance. The radiocarpal group showed significant improvements in distal radius and carpal alignment parameters, except for the radiolunate angle, radioscaphoid angle, and capitolunate angle. The radiocarpal group exhibited an overall decrease in range of motion compared with that of the midcarpal group. Severity of the fracture and time taken from injury to corrective osteotomy correlated with the ability to correct carpal radiographic parameters in dorsally angulated malunions of the distal radius, especially beyond 40 weeks. Conclusions: The severity of the initial fracture and time taken from injury to corrective osteotomy correlate with the ability to correct radiographic parameters in dorsally angulated malunions of the distal radius. Early correction of distal radius malunions is recommended, especially in radiocarpal malalignment patterns. A useful analysis for predicting midcarpal and radiocarpal adaptation patterns is the direct measurement of the distal articular surface of the radius to the lunate, termed the relative-radiolunate angle. Type of study/level of evidence: Therapeutic IV.

Combination vardenifil and tadalifil drug induced liver injury; case report and review of the literature of liver injury associated with phosphodiesterase type 5 inhibitors.

Background: Phosphodiesterase type 5 inhibitors (PDE5I) are prescribed for erectile dysfunction and pulmonary hypertension. Despite its widespread use, there are only seven cases of drug-induced liver injury (DILI) associated with PDE5I, none associated with vardenafil or avanafil. We report a patient who had taken vardenafil and tadalafil individually for several years without developing symptoms of liver injury. However, after taking vardenafil and tadalafil together on 2 consecutive days, he developed severe cholestasis. Methods: Causality was determined using Roussel Uclaf causality assessment method (RUCAM). Results: The patient is a 72-year-old White man in excellent health who drank 2 units of alcohol, three times/week. Previously, he had used vardenafil for more than 2 years and tadalafil for 3 months as single agent for erectile dysfunction without any complications. He took vardenafil and tadalafil for 2 consecutive days and 5 days later, he developed dyspepsia, loss of appetite, jaundice, and intense itching. Liver tests showed mixed cholestatic/hepatocellular pattern of injury. Histology showed marked cholestasis with minimal inflammation. He remained cholestatic for 5 weeks before a full recovery 2 months later. The patient then resumed vardenafil monotherapy with no recurrent liver dysfunction. RUCAM causality score 7 indicates that the combination of PDE5I is probable cause of liver injury. The similarities among the eight cases of PDE5I DILI include a relatively short latency, cholestatic histological features, and complete recovery. Biochemical pattern of liver injury is variable. Conclusions: PDE5I DILI is a rare event that can result in severe acute liver injury.

High-speed 4 × 4 silicon photonic plasma dispersive switch, operating at the 2†µm waveband.

The escalating need for expansive data bandwidth, and the resulting capacity constraints of the single mode fiber (SMF) have positioned the 2-µm waveband as a prospective window for emerging applications in optical communication. This has initiated an ecosystem of silicon photonic components in the region driven by CMOS compatibility, low cost, high efficiency and potential for large-scale integration. In this study, we demonstrate a plasma dispersive 4 × 4 photonic switch operating at the 2-µm waveband with the highest switching speed. The demonstrated switch operates across a 45-nm bandwidth, with 10-90% rise and 90-10% fall time of 1.78 ns and 3.02 ns respectively. In a 4 × 4 implementation, crosstalk below -15 dB and power consumption lower than 19.15 mW across all 16 optical paths are indicated. This result brings high-speed optical switching to the portfolio of devices at the promising waveband.

Bridge Plating of a First Proximal Phalanx Intra-articular Base Fracture-Benefits Over External Fixation.

A 62-year-old right-handed man presented with an intra-articular fracture of the proximal phalanx base of the right thumb after a motor vehicle accident. Computed tomography revealed severe comminution, apex volar angulation, and minimal bone stock at the proximal phalanx base. The patient consented to open reduction internal fixation with a locking plate to bridge the fracture and cancellous bone grafting of the distal radius. The hardware was removed at 8 weeks, without complications. The patient began therapy, and at 19 weeks following the surgery, the patient's thumb metacarpophalangeal joint motion was 10° to 30° and the interphalangeal motion was 30° to 50°. Radiographs showed fracture union and proper alignment, with modest shortening. The patient was satisfied with this result. Bridge plating may be an alternative to external fixation for certain thumb fractures, with the potential to maintain alignment and articular congruity while permitting earlier return to activities of daily living and avoiding the risk of pin-track infections.

Modal gain characteristics of a two-section InGaAs/GaAs double quantum well passively mode-locked laser with asymmetric waveguide.

Monolithic two-section InGaAs/GaAs double quantum well (DQW) passively mode-locked lasers (MLLs) with asymmetric waveguide, consisting of the layers of p-doped AlGaAs waveguide and no-doped InGaAsP waveguide, emitting at ~ 1.06 µm, with a fundamental repetition rate at ~ 19.56 GHz have been demonstrated. Modal gain characteristics, such as a gain bandwidth and a gain peak wavelength of the MLL, as a function of the saturable absorber (SA) bias voltage (Va) as well as the injection current of gain section (Ig), were investigated by the Hakki-Paoli method. With the increase of Va, the lasing wavelength and net modal gain peak of the MLL both exhibited red-shifts to longer wavelength significantly, while the modal gain bandwidth was narrowed. Both the net modal gain bandwidth and gain peak of the MLL followed a polynomial distribution versus the reverse bias at the absorber section. In addition, for the first time, it was found that Va had an obvious effect on the modal gain characteristics of the MLL.

Optical frequency comb generation from a 1.65 µm single-section quantum well laser.

Optical frequency combs (OFCs) in the 1.65 µm wavelength band are promising for methane sensing and extended high-capacity optical communications. In this work, a frequency-modulated (FM) OFC is generated from a 1.65 µm single-section quantum well laser. This is characterized by a 1 kHz-wide beatnote signal at ∼19.4 GHz. Typical FM optical spectra are shown and optical linewidth of the OFC narrows through the mutual injection locking process in the comb formation. No distinct pulse train is observed on oscilloscope, which conforms with the FM operation. Furthermore, to add further evidence that four-wave mixing (FWM) is the driving mechanism of the comb formation, FWM frequency conversion characterization is conducted on a semiconductor optical amplifier (SOA) fabricated together with the tested laser. An efficiency of ∼-30 dB confirms the capability of FM mode locking.

Compact silicon photonic hybrid ring external cavity (SHREC)/InGaSb-AlGaAsSb wavelength-tunable laser diode operating from 1881-1947†nm.

In recent years, the 2 µm waveband has been gaining significant attention due to its potential in the realization of several key technologies, specifically, future long-haul optical communications near the 1.9 µm wavelength region. In this work, we present a hybrid silicon photonic wavelength-tunable diode laser with an operating range of 1881-1947 nm (66 nm) for the first time, providing good compatibility with the hollow-core photonic bandgap fiber and thulium-doped fiber amplifier. Room-temperature continuous-wave operation was achieved with a favorable on-chip output power of 28 mW. Stable single-mode lasing was observed with side-mode suppression ratio up to 35 dB. Besides the abovementioned potential applications, the demonstrated wavelength region will find critical purpose in H2O spectroscopic sensing, optical logic, signal processing as well as enabling the strong optical Kerr effect on Si.

Mutational Analysis of Lassa Virus Glycoprotein Highlights Regions Required for Alpha-Dystroglycan Utilization.

Lassa virus (LASV) is an enveloped RNA virus endemic to West Africa and responsible for severe cases of hemorrhagic fever. Virus entry is mediated by the glycoprotein complex consisting of a stable-signal peptide, a receptor-binding subunit, GP1, and a viral-host membrane fusion subunit, GP2. Several cellular receptors can interact with the GP1 subunit and mediate viral entry, including alpha-dystroglycan (αDG) and lysosome-associated membrane protein 1 (LAMP1). In order to define the regions within GP1 that interact with the cellular receptors, we implemented insertional mutagenesis, carbohydrate shielding, and alanine scanning mutagenesis. Eighty GP constructs were engineered and evaluated for GP1-GP2 processing, surface expression, and the ability to mediate cell-to-cell fusion after low-pH exposure. To examine virus-to-cell entry, 49 constructs were incorporated onto vesicular stomatitis virus (VSV) pseudoparticles and transduction efficiencies were monitored in HAP1 and HAP1-ΔDAG1 cells that differentially produce the αDG cell surface receptor. Seven constructs retained efficient transduction in HAP1-ΔDAG1 cells yet poorly transduced HAP1 cells, suggesting that they are involved in αDG utilization. Residues H141, N146, F147, and Y150 cluster at the predicted central core of the trimeric interface and are important for GP-αDG interaction. Additionally, H92A-H93A, 150HA, 172HA, and 230HA displayed reduced transduction in both HAP1 and HAP1-ΔDAG1 cells, despite efficient cell-to-cell fusion activity. These mutations may interfere with interactions with the endosomal receptor LAMP1 or interfere at another stage in entry that is common to both cell lines. Insight gained from these data can aid in the development of more-effective entry inhibitors by blocking receptor interactions.IMPORTANCE Countries in which Lassa virus is endemic, such as Nigeria, Sierra Leone, Guinea, and Liberia, usually experience a seasonal outbreak of the virus from December to March. Currently, there is neither a preventative vaccine nor a therapeutic available to effectively treat severe Lassa fever. One way to thwart virus infection is to inhibit interaction with cellular receptors. It is known that the GP1 subunit of the Lassa glycoprotein complex plays a critical role in receptor recognition. Our results highlight a region within the Lassa virus GP1 protein that interacts with the cellular receptor alpha-dystroglycan. This information may be used for future development of new Lassa virus antivirals.

Non-nucleoside inhibitors of HCV polymerase NS5B. Part 2: Synthesis and structure-activity relationships of benzothiazine-substituted quinolinediones.

A new series of benzothiazine-substituted quinolinediones were evaluated as inhibitors of HCV polymerase NS5B. SAR studies on this series revealed a methyl sulfonamide group as a high affinity feature. Analogues with this group showed submicromolar potencies in the HCV cell based replicon assay. Pharmacokinetic and toxicology studies were also performed on a selected compound (34) to evaluate in vivo properties of this new class of inhibitors of HCV NS5B polymerase.