Near-Temperature-Independent Electron Transport Well beyond Expected Quantum Tunneling Range via Bacteriorhodopsin Multilayers.

A key conundrum of biomolecular electronics is efficient electron transport (ETp) through solid-state junctions up to 10 nm, often without temperature activation. Such behavior challenges known charge transport mechanisms, especially via nonconjugated molecules such as proteins. Single-step, coherent quantum-mechanical tunneling proposed for ETp across small protein, 2-3 nm wide junctions, but it is problematic for larger proteins. Here we exploit the ability of bacteriorhodopsin (bR), a well-studied, 4-5 nm long membrane protein, to assemble into well-defined single and multiple bilayers, from ∼9 to 60 nm thick, to investigate ETp limits as a function of junction width. To ensure sufficient signal/noise, we use large area (∼10-3 cm2) Au-protein-Si junctions. Photoemission spectra indicate a wide energy separation between electrode Fermi and the nearest protein-energy levels, as expected for a polymer of mostly saturated components. Junction currents decreased exponentially with increasing junction width, with uniquely low length-decay constants (0.05-0.5 nm-1). Remarkably, even for the widest junctions, currents are nearly temperature-independent, completely so below 160 K. While, among other things, the lack of temperature-dependence excludes, hopping as a plausible mechanism, coherent quantum-mechanical tunneling over 60 nm is physically implausible. The results may be understood if ETp is limited by injection into one of the contacts, followed by more efficient charge propagation across the protein. Still, the electrostatics of the protein films further limit the number of charge carriers injected into the protein film. How electron transport across dozens of nanometers of protein layers is more efficient than injection defines a riddle, requiring further study.

Volumetric assessment of the nose after primary unilateral cleft rhinoplasty using Laberge's technique.

BACKGROUND: There is a lack of standardized surgery for cleft rhinoplasty. We felt that the technique described by Dr Louise Caouette Laberge is an ideal way to approach this problem, thus we tried to quantify the outcome of surgery by volumetric assessment. MATERIAL AND METHOD: We recorded 3D images using an Artec scanner and performed volume calculations of the cleft side and noncleft side of the nose. These readings were taken once in the preoperative and then 2 weeks postoperative. Another scan of the face was performed 2 years after the surgery to compare the volumes of the cleft and noncleft side nostril. RESULTS: Of the 31 patients with unilateral cleft lip operated on (mean age 3-8 months), we found a significant increase in the cleft side volume at 3 weeks postoperative from 3.95 mm3 to 5.65 mm3 (p < 0.001 on paired t-test). A repeat scan done on the study population at 2 years postoperative found that the mean volume of the cleft side was 30.43 mm3 (standard deviation [SD], 2.49) and that of the normal side was 30.82 mm3 (SD, 2.51). An independent t-test found that there was no significant difference between the two volumes (p > 0.05) CONCLUSION: The use of volumetric data in the evaluation of postoperative outcomes provides an objective criterion for assessing the aesthetics as well as the growth. Our study concludes that the Laberge technique provides a good aesthetic outcome with minimal scarring for the management of cleft nose and lip with the anterior palate.

Biotin Binding Hardly Affects Electron Transport Efficiency across Streptavidin Solid-State Junctions.

The electron transport (ETp) efficiency of solid-state protein-mediated junctions is highly influenced by the presence of electron-rich organic cofactors or transition metal ions. Hence, we chose to investigate an interesting cofactor-free non-redox protein, streptavidin (STV), which has unmatched strong binding affinity for an organic small-molecule ligand, biotin, which lacks any electron-rich features. We describe for the first time meso-scale ETp via electrical junctions of STV monolayers and focus on the question of whether the rate of ETp across both native and thiolated STV monolayers is influenced by ligand binding, a process that we show to cause some structural conformation changes in the STV monolayers. Au nanowire-electrode-protein monolayer-microelectrode junctions, fabricated by modifying an earlier procedure to improve the yields of usable junctions, were employed for ETp measurements. Our results on compactly integrated, dense, uniform, ∼3 nm thick STV monolayers indicate that, notwithstanding the slight structural changes in the STV monolayers upon biotin binding, there is no statistically significant conductance change between the free STV and that bound to biotin. The ETp temperature (T) dependence over the 80-300 K range is very small but with an unusual, slightly negative (metallic-like) dependence toward room temperature. Such dependence can be accounted for by the reversible structural shrinkage of the STV at temperatures below 160 K.

Analysis of clinical and patient-reported outcomes in post-ELAPE perineal reconstruction with IGAP flap - A 5-year review.

BACKGROUND: Extralevator abdominoperineal excisions (ELAPE) are now the accepted treatment option for low rectal cancers, which result in large perineal defects necessitating reconstruction. The aim of our study was to assess the clinical outcomes as well as the quality-of-life parameters (QOLP) following these reconstructions. METHODS: A series of 27 patients who underwent ELAPE and immediate reconstruction with inferior gluteal artery perforator flaps (IGAP) between December 2013 to December 2018 were retrospectively analysed on patient demographics, disease and treatment, complications, and QOLP. RESULTS: With a mean age of 71.6 years, all patients had low rectal cancers and underwent ELAPE (24 open, 3 lap-assisted) and immediate IGAP flap reconstruction. The follow-up period was 1 year. The overall perineal early minor complication rate was 25.9% and the early major complication rate of 14.8%. QOLP, such as tolerance to sit, perineal pain, perineal aesthetics, showed high patient satisfaction of 77.7%, 40.74%, and 66.6%, respectively at 1 year. The perineal hernia rate was 14.8% with all patients being female (p 0.0407; significant). CONCLUSION: IGAP flaps are a reliable option for reconstructing post-ELAPE defects with good patient satisfaction and outcomes.

Molecularly resolved, label-free nucleic acid sensing at solid-liquid interface using non-ionic DNA analogues.

Nucleic acid-based biosensors, where the capture probe is a nucleic acid, e.g., DNA or its synthetic analogue xeno nucleic acid (XNA), offer interesting ways of eliciting clinically relevant information from hybridization/dehybridization signals. In this respect, the application of XNA probes is attractive since the drawbacks of DNA probes might be overcome. Within the XNA probe repertoire, peptide nucleic acid (PNA) and morpholino (MO) are promising since their backbones are non-ionic. Therefore, in the absence of electrostatic charge repulsion between the capture probe and the target nucleic acid, a stable duplex can be formed. In addition, these are nuclease-resistant probes. Herein, we have tested the molecularly resolved nucleic acid sensing capacity of PNA and MO capture probes using a fluorescent label-free single molecule force spectroscopy approach. As far as single nucleobase mismatch discrimination is concerned, both PNA and MO performed better than DNA, while the performance of the MO probe was the best. We propose that the conformationally more rigid backbone of MO, compared to the conformationally flexible PNA, is an advantage for MO, since the probe orientation can be made more upright on the surface and therefore MO can be more effectively accessed by the target sequences. The performance of the XNA probes has been compared to that of the DNA probe, using fixed nucleobase sequences, so that the effect of backbone variation could be investigated. To our knowledge, this is the first report on molecularly resolved nucleic acid sensing by non-ionic capture probes, here, MO and PNA.

Successful patient outcome following surgery of carotid body tumor and temporary hypoglossal nerve dysfunction.

Carotid body tumors, also known as paragangliomas or chemodectomas, are rare tumors. They are mostly benign slow-growing tumors arising from neural crest cells, but can give rise to complications because of their location and close relation to carotid vessels and cranial nerves. A 40-year male patient diagnosed with a carotid body tumor is discussed along with a review of cranial nerve complications associated with the management of carotid body tumors. This case highlights the complete recovery after a temporary hypoglossal nerve deficit following surgery. Another important aspect is that syncopal attacks might occur in carotid body tumors and early surgery is required to prevent complications.

Ulnar-Basilic Arteriovenous Fistula for Hemodialysis Access: Utility as the "Second Procedure" after Radio Cephalic Fistula.

Objectives: As per standard guidelines, the recommended order of arteriovenous fistula (AVF) creation for hemodialysis (HD) access is radiocephalic (RC), followed by proximal elbow fistulas and arteriovenous graft. Although ulnar-basilic (UB) fistula has been an alternative to RC-AVF, still this procedure searches clear recommendations. We present here our experience on UB-AVF as the preferred "second procedure" instead of proximal fistula after the RC-AVF. Methods: Forty-two UB-AVF were created in nonfeasible and failed RC-AVF cases between 2016 and 2018. They were reviewed retrospectively and outcomes were compared with 480 RC-AVF constructed within the same period. Results: The primary patency at 18 months was 73.8%, 69.6% and mean maturation time was 33.7±6.6 days, 32.1±4.7 days for UB-AVF and RC-AVF respectively (p>0.05). Conclusion: Our altered order of preference enabled us to create all the first-time fistula in the distal forearm, providing all the advantages of distal fistula like RC-AVF and avoiding proximal fistula, improved patient convenience and short-term benefit. In an inference that may be used for references and needs support from a larger sample and longer duration study from other centers, UB-AVF may be considered as the second option after RC-AVF depending on the clinical scenario.

How stable are the collagen and ferritin proteins for application in bioelectronics?

One major obstacle in development of biomolecular electronics is the loss of function of biomolecules upon their surface-integration and storage. Although a number of reports on solid-state electron transport capacity of proteins have been made, no study on whether their functional integrity is preserved upon surface-confinement and storage over a long period of time (few months) has been reported. We have investigated two specific cases-collagen and ferritin proteins, since these proteins exhibit considerable potential as bioelectronic materials as we reported earlier. Since one of the major factors for protein degradation is the proteolytic action of protease, such studies were made under the action of protease, which was either added deliberately or perceived to have entered in the reaction vial from ambient environment. Since no significant change in the structural characteristics of these proteins took place, as observed in the circular dichroism and UV-visible spectrophotometry experiments, and the electron transport capacity was largely retained even upon direct protease exposure as revealed from the current sensing atomic force spectroscopy experiments, we propose that stable films can be formed using the collagen and ferritin proteins. The observed protease-resistance and robust nature of these two proteins support their potential application in bioelectronics.

Lower Extremity Marjolin's Ulcer Reconstruction With Free Anterolateral Thigh Flap: A Case Series of 11 Patients.

Background Marjolin's ulcer (MU) of lower extremities usually presents with scar contracture and functional disability. They often follow an aggressive course and poor outcome, and require early radical removal. Split-thickness skin grafts, local flaps, or amputation are commonly practiced surgical options for MU. Though free flaps are gaining popularity for various oncoplastic reconstruction, they are not frequently used for MU. A free anterolateral thigh (ALT) flap may have a beneficial role as it provides simultaneous coverage for a large defect after radical tumor and scar excision. Methods Between January 2015 and December 2018, 11 patients with lower limb MU reconstructed with free ALT flap were reviewed retrospectively for the surgical procedure, recurrences, and functional outcomes. Results Mean dimensions of the defect and flaps were 8 cm × 6 cm and 18.91 cm × 11 cm, respectively, and total flap coverage was obtained in nine cases. Marginal flap loss was noted in one and residual contracture in two cases. Functional improvement of the limb was achieved in all cases. Recurrence or disease-related mortality was not seen in any patient after a mean follow-up of 35.82 months. Conclusions Free ALT flap reconstruction of MU of extremity facilitates most radical tumor and scar-contracture removal and thus reduces the chances of re-ulceration. It facilitates local radiotherapy protocol with the provision of immediate durable coverage. Thus, it has a beneficial role other than a secondary reconstructive procedure. Moreover, an added benefit may be obtained with a "flow-through' flap" to avoid amputation and improve functional outcomes.

Management of ulcerated finger pad tophi.

Finger pad tophi are an unusual but not very rare presentation of uncontrolled gout. Unlike tophaceous lesions of other locations, finger pad tophi are often difficult to diagnose at presentation due to resemblance to a variety of nodular lesions, coexistence with other connective tissue disorders and sometimes occurrence in asymptomatic hyperuricemia. They also pose a therapeutic dilemma due to a lack of clear treatment guidelines. Several case reports of finger pad tophi have been published before, focusing mainly on diagnosis and medical management. We discuss here a case of thumb pad tophi as primary presentation of undiagnosed asymptomatic hyperuricemia and treated surgically with excision and full-thickness skin graft along with urate-lowering therapy. This article highlights the diagnosis and treatment of finger pad tophi. We also discuss the surgical management of tophaceous lesions of hands and digits.

The Revolving Door Flap: Revisiting an Elegant but Forgotten Flap for Ear Defect Reconstruction.

Background The revolving door flap, although well described in the literature, is not widely used in general plastic surgery practice. The flap has been used for anterior auricular and conchal defects and is considered elegant for its unique flap design and peculiarity of flap harvest. However, due to its use for a very specific purpose and unique flap harvest technique that may be difficult to grasp, the flap is not very popular in reconstructive practice. Objectives This study aims to evaluate the understanding and learning curve of the revolving door flap, assess surgical outcome, and reemphasize its utility and elegance in reconstruction of ear defects. Methodology This is a case series of nine surgeries performed between January 2014 and 2018. Three cases were performed by the senior author and six cases by two junior authors. Patients were observed for complications and aesthetic outcomes. Results The mean dimension of the flaps was 27.22 mm × 22.78 mm. The mean operative time was 56.56 minutes (standard deviation 22.50, standard error of the mean 7.5). Flap congestion was noted in three cases postoperatively which resolved completely by the second week. Major "pinning" of the ear was noted in four cases. Conclusion Though infrequently performed, the revolving door flap has an easy learning curve once the proper harvest technique and flap movement has been grasped. The flap harvest is convenient, safe, and yields predictable results. Not only is total or partial flap loss extremely rare, the flap is sensate, color match is good, auricular contour is maintained, and the donor site can be closed primarily and remains well hidden.

Electron Transport in Muscle Protein Collagen.

In recent times, collagen, which is one of the most abundant proteins in animals, has appeared to be an attractive candidate for biomaterial applications, for example, in medical implants and wearable electronics. This is because collagen is water-insoluble, biocompatible, and nontoxic. In addition, films of different sizes and shapes can be made using this protein as it is malleable and elastic in nature. However, its electron transport capacity or its absence has remained largely untested so far. Therefore, in this work, the electron transport behavior of collagen has been studied in both film and single-fiber states in a local probe configuration using current-sensing atomic force spectroscopy (CSAFS). From the CSAFS analyses, the electronic (transport) band gap of collagen has been estimated. It has been found that collagen behaves as a wide band gap semiconductor (near-insulating) in a variety of experimental conditions. The transition to a semiconducting material with a low electronic band gap and a nearly 1000-fold enhancement of current (picoampere to nanoampere level) occurs by metal ion treatment (here, Fe3+) of the native collagen. To the best of our knowledge, this is the first report of a molecular level study of the electron transport behavior of collagen proteins and estimation of transport band gap values of collagen and metalated collagen.

Nanoscale On-Silico Electron Transport via Ferritins.

Silicon is a solid-state semiconducting material that has long been recognized as a technologically useful one, especially in electronics industry. However, its application in the next-generation metalloprotein-based electronics approaches has been limited. In this work, the applicability of silicon as a solid support for anchoring the iron-storage protein ferritin, which has a semiconducting iron nanocore, and probing electron transport via the ferritin molecules trapped between silicon substrate and a conductive scanning probe has been investigated. Ferritin protein is an attractive bioelectronic material because its size (X-ray crystallographic diameter ∼12 nm) should allow it to fit well in the larger tunnel gaps (>5 nm), fabrication of which is relatively more established, than the smaller ones. The electron transport events occurring through the ferritin molecules that are covalently anchored onto the MPTMS-modified silicon surface could be detected at the molecular level by current-sensing atomic force spectroscopy (CSAFS). Importantly, the distinct electronic signatures of the metal types (i.e., Fe, Mn, Ni, and Au) within the ferritin nanocore could be distinguished from each other using the transport band gap analyses. The CSAFS measurements on holoferritin, apoferritin, and the metal core reconstituted ferritins reveal that some of these ferritins behave like n-type semiconductors, while the others behave as p-type semiconductors. The band gaps for the different ferritins are found to be within 0.8 to 2.6 eV, a range that is valid for the standard semiconductor technology (e.g., diodes based on p-n junction). The present work indicates effective on-silico integration of the ferritin protein, as it remains functionally viable after silicon binding and its electron transport activities can be detected. Potential use of the ferritin-silicon nanohybrids may therefore be envisaged in applications other than bioelectronics, too, as ferritin is a versatile nanocore-containing biomaterial (for storage/transport of metals and drugs) and silicon can be a versatile nanoscale solid support (for its biocompatible nature).

Fast Bayesian inference of optical trap stiffness and particle diffusion.

Bayesian inference provides a principled way of estimating the parameters of a stochastic process that is observed discretely in time. The overdamped Brownian motion of a particle confined in an optical trap is generally modelled by the Ornstein-Uhlenbeck process and can be observed directly in experiment. Here we present Bayesian methods for inferring the parameters of this process, the trap stiffness and the particle diffusion coefficient, that use exact likelihoods and sufficient statistics to arrive at simple expressions for the maximum a posteriori estimates. This obviates the need for Monte Carlo sampling and yields methods that are both fast and accurate. We apply these to experimental data and demonstrate their advantage over commonly used non-Bayesian fitting methods.

Simultaneous measurement of mass and rotation of trapped absorbing particles in air.

We trap absorbing micro-particles in air by photophoretic forces generated using a single loosely focused Gaussian trapping beam. We measure a component of the radial Brownian motion of a trapped particle cluster and determine the power spectral density, mean squared displacement, and normalized position and velocity autocorrelation functions to characterize the photophoretic body force in a quantitative fashion for the first time. The trapped particles also undergo spontaneous rotation due to the action of this force. This is evident from the spectral density that displays clear peaks at the rotation and the particles' inertial resonance frequencies. We fit the spectral density to the well-known analytical function derived from the Langevin equation, measure the resonance and rotation frequencies, and determine the values for particle mass that we verify at different trapping laser powers with reasonable accuracy.

Using Brownian motion to measure shape asymmetry in mesoscopic matter using optical tweezers.

We propose a new method for quantifying shape asymmetry on the mesoscopic scale. The method takes advantage of the intrinsic coupling between rotational and translational Brownian motion (RBM and TBM, respectively) which happens in the case of asymmetric particles. We determine the coupling by measuring different correlation functions of the RBM and TBM for single, morphologically different, weakly trapped red blood cells in optical tweezers. The cells have different degrees of asymmetry that are controllably produced by varying the hypertonicity of their aqueous environment. We demonstrate a clear difference in the nature of the correlation functions both qualitatively and quantitatively for three types of cells having a varying degree of asymmetry. This method can have a variety of applications ranging from early stage disease diagnosis to quality control in microfabrication.

Simultaneous detection of rotational and translational motion in optical tweezers by measurement of backscattered intensity.

We describe a simple yet powerful technique of simultaneously measuring both translational and rotational motion of mesoscopic particles in optical tweezers by measuring the backscattered intensity on a quadrant photodiode (QPD). While the measurement of translational motion by taking the difference of the backscattered intensity incident on adjacent quadrants of a QPD is well known, we demonstrate that rotational motion can be measured very precisely by taking the difference between the diagonal quadrants. The latter measurement eliminates the translational component entirely and leads to a detection sensitivity of around 50 mdeg at S/N of 2 for angular motion of a driven microrod. The technique is also able to resolve the translational and rotational Brownian motion components of the microrod in an unperturbed trap and can be very useful in measuring translation-rotation coupling of micro-objects induced by hydrodynamic interactions.