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Objective: Venous thoracic outlet syndrome (VTOS), a compression syndrome of the subclavian vein at the costoclavicular junction, is commonly treated with first rib resection. This invasive procedure carries a risk of serious complications. The purpose of this single-center cross-sectional study was to evaluate the long-term outcome of non-bony decompression by resection of the subclavius muscle and tendon and to provide a detailed description of the procedure., Methods: Patients who underwent rib-sparing decompression for VTOS between July 2014 and September 2023 were analyzed using clinical and radiological examinations. Patient-reported measures were used to assess functional disability and residual symptoms (Disabilities of the Arm, Shoulder and Hand-DASH) and disease-specific quality of life and symptoms (VEINES-QOL/SYM)., Results: Ten patients were included in the study. Seven were treated for Paget-Schroetter syndrome and three for McCleery syndrome. At a mean follow-up of 45.4 (standard deviation [SD] 31.0) months, all patients reported significant resolution of initial symptoms with patent vasculature on Doppler ultrasonography. All patients had a Villalta post-thrombotic syndrome score of <4, indicating the absence of post-thrombotic syndrome. A mean DASH score of 3.8 (SD 5.3) indicated minimal functional disability. Patients reported minimal overall impact on their quality of life, as reflected by a mean VEINES-QOL score of 92.6 (SD 8.9), and low severity of venous symptoms, as indicated by a mean VEINES-SYM score of 92.7 (SD 9.8)., Conclusion: Our analysis suggests that non-bony decompression with resection of the subclavius muscle and tendon is a safe and effective intervention for the definitive treatment of VTOS that is less invasive than first rib resection., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Projects for workplace health promotion (WHP) for back pain traditionally focus exclusively on work-related but not on leisure-time stress on the spine. We developed a comprehensive WHP project on the back health of hospital workers regardless of the physical characteristics of their work and compared its effects on sedentary and physically active hospital workers., Methods: Study assessments were carried out before and six months after participation in the WHP intervention. The primary outcome parameter was back pain (Oswestry Disability Index, ODI). Anxiety (Generalized Anxiety Disorder-7), work ability (Work Ability Index), depression (Patient Health Questionnaire-9), stress (Perceived Stress Scale-10), and quality of life (Short Form-36) were assessed via questionnaires as secondary outcome parameters. Physical performance was measured via the 30 seconds Sit-to-Stand test (30secSTS)., Results: Sixty-eight healthcare workers with non-specific back pain were included in the evaluation study of the WHP project "Back Health 24/7/365". After six months, back pain, physical performance, and self-perceived physical functioning (SF-36 Physical Functioning subscale) improved significantly in both groups. Not a single parameter showed an interaction effect with the group allocation., Conclusions: A comprehensive WHP-intervention showed significant positive effects on hospital workers regardless of the physical characteristics of their work.

Background: Botulinum toxin injection is the accepted standard treatment for synkinesis and gustatory hyperlacrimation in patients with facial paralysis. However, poor injection accuracy can result in inconsistent treatment outcomes, variable treatment durations, and complications. Ultrasound guidance should increase injection accuracy in the facial region; however, this has not been proven., Methods: Twenty-six hemifaces of nonembalmed cadavers were studied in a randomized split-face manner. Ink was injected with ultrasound or landmark guidance into the lacrimal gland and three common synkinetic muscles: the orbicularis oculi, depressor anguli oris, and mentalis. Injection accuracy was evaluated using several measures., Results: Using ultrasound guidance, most ink (>50%) was found inside the correct target in 88% of cases, compared with 50% using landmark guidance ( P < 0.001). This was most pronounced in the lacrimal gland (62% versus 8%), depressor anguli oris (100% versus 46%), and mentalis (100% versus 54%) ( P < 0.05). All ink was found inside the correct target (no ink outside) in 65% using ultrasound guidance versus 29% without ( P < 0.001). Injection accuracy (any ink in target) was 100% when using ultrasound guidance versus 83% without ( P < 0.01). Twenty-three percent of the landmark-guided depressor anguli oris injections stained the facial artery ( P = 0.22)., Conclusions: Ultrasound guidance significantly increased injection accuracy and reduced the amount of ink lost in the surrounding tissue compared with landmark guidance. Clinical trials are needed to explore the effects of ultrasound guidance on treatment outcome, duration, and complications in patients with facial paralysis., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Background: Myectomies of the lower lip depressor muscles have unexplained high failure rates. This study aimed to examine the depressor anguli oris (DAO) muscle using high-resolution ultrasound to identify potential anatomical explanations for surgical failures and to determine the accuracy of utilizing preoperative ultrasound assessment to improve myectomies., Methods: Anatomical features of DAO and the surrounding anatomy were examined in 38 hemifaces of human body donors using high-resolution ultrasound and dissection., Results: The ultrasound and dissection measurements showed the DAO muscle width to be 16.2 ± 2.9 versus 14.5 ± 2.5 mm, respectively, and the location of the lateral muscle border 54.4 ± 5.7 versus 52.3 ± 5.4 mm lateral to the midline. In 60% of the cases, the facial artery was either completely covered by lateral DAO muscle fibers or was found to be in direct contact with the lateral border. Significant muscle fiber continuity was present between the DAO and surrounding muscles in 5% of cases, whereas continuity between the depressor labii inferioris and surrounding muscles was considerably more common and pronounced., Conclusions: High-resolution ultrasound can accurately reveal important preoperative anatomical information in myectomies. Two potential explanations for the surgical failures were discovered: an overlap of lateral DAO muscle fibers over the facial artery could lead to inadequate resections and continuity with the surrounding muscles might lead to muscle function takeover despite adequate resections. Both can be uncovered preoperatively by the surgeon through a brief, directed ultrasound examination, which may allow for modification of the surgical plan to reduce surgical failure., Competing Interests: Declaration of Competing Interest The authors declare that they have no financial conflicts of interest., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

The discovered light modulation capabilities of diatom silicious valves make them an excellent toolkit for photonic devices and applications. In this work, a reproducible surface-enhanced Raman scattering (SERS) enhancement was achieved with hybrid substrates employing diatom silica valves coated with an ultrathin uniform gold film. Three structurally different hybrid substrates, based on the valves of three dissimilar diatom species, have been compared to elucidate the structural contribution to SERS enhancement. The comparative analysis of obtained results showed that substrates containing cylindrical Aulacoseira sp. valves achieved the highest enhancement, up to 14-fold. Numerical analysis based on the frequency domain finite element method was carried out to supplement the experimental results. Our results demonstrate that diatom valves of different shapes can enhance the SERS signal, offering a toolbox for SERS-based sensors, where the magnitude of the enhancement depends on valve geometry and ultrastructure.

Background  The temporalis muscle flap transfer with fascia lata augmentation (FLA) is a promising method for smile reconstruction after facial palsy. International literature lacks a detailed anatomical analysis of the temporalis muscle (TPM) combined with fascia lata (FL) augmentation. This study aims to describe the muscle's properties and calculate the length of FL needed to perform the temporalis muscle flap transfer with FLA. Methods  Twenty nonembalmed male (m) and female (f) hemifacial cadavers were dissected to investigate the temporalis muscle's anatomy. Results  The calculated minimum length of FL needed is 7.03cm (f) and 5.99cm (m). The length of the harvested tendon is 3.16cm/± 1.32cm (f) and 3.18/± 0.73cm (m). The length of the anterior part of the temporalis muscle (aTPM) is 4.16/± 0.80cm (f) and 5.30/± 0.85cm (m). The length of the posterior part (pTPM) is 5.24/± 1.51cm (f) and 6.62/± 1.03cm (m). The length from the most anterior to the most posterior point (aTPMpTPM) is 8.60/± 0.98cm (f) and 10.18/± 0.79cm (m). The length from the most cranial point to the distal tendon (cTPMdT) is 7.90/± 0.43cm (f) and 9.79/± 1.11cm (m). Conclusions  This study gives basic information about the temporalis muscle and its anatomy to support existing and future surgical procedures in their performance. The recommended minimum length of FL to perform a temporalis muscle transfer with FLA is 7.03cm for female and 5.99cm for male, and minimum width of 3 cm. We recommend harvesting some extra centimeters to allow adjusting afterward., Competing Interests: Conflict of Interest C.H.J.T. is an editorial board member of the journal but was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported., (The Korean Society of Plastic and Reconstructive Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: Donor nerve options for lower lip reanimation are limited in patients undergoing oncological resection of the facial nerve. The ansa cervicalis nerve (ACN) is an advantageously situated donor with great potential but has not been examined in detail. In the current study, the anatomical technical feasibility of selective ACN to marginal mandibular nerve (MMN) transfer for restoration of lower lip tone and symmetry was explored. A clinical case is presented., Methods: Dissections were conducted in 21 hemifaces in non-embalmed human cadavers. The maximal harvestable length of ACN was measured and transfer to MMN was simulated. A 28-year-old male underwent ACN-MMN transfer after parotidectomy (carcinoma) and was evaluated 12 months post-operatively (modified Terzis' Lower Lip Grading Scale [25 observers] and photogrammetry)., Results: The harvestable length of ACN was 100 ± 12 mm. A clinically significant anatomical variant ("short ansa") was present in 33% of cases (length: 37 ± 12 mm). Tensionless coaptation was possible in all cases only when using a modification of the surgical technique in "short ansa" cases (using an infrahyoid muscle nerve branch as an extension). The post-operative course of the clinical case was uneventful without complications, with improvement in tone, symmetry, and function at the lower lip at 12-month post-operative follow-up., Conclusions: Selective ACN-MMN nerve transfer is anatomically feasible in facial paralysis following oncological ablative procedures. It allows direct nerve coaptation without significant donor site morbidity. The clinical case showed good outcomes 12 months post-operatively. A strategy when encountering the "short ansa" anatomical variant in clinical cases is proposed., (© 2022 The Authors. Microsurgery published by Wiley Periodicals LLC.)

Siliceous diatom frustules present a huge variety of shapes and nanometric pore patterns. A better understanding of the light modulation by these frustules is required to determine whether or not they might have photobiological roles besides their possible utilization as building blocks in photonic applications. In this study, we propose a novel approach for analyzing the near-field light modulation by small pennate diatom frustules, utilizing the frustule of Gomphonema parvulum as a model. Numerical analysis was carried out for the wave propagation across selected 2D cross-sections in a statistically representative 3D model for the valve based on the finite element frequency domain method. The influences of light wavelength (vacuum wavelengths from 300 to 800 nm) and refractive index changes, as well as structural parameters, on the light modulation were investigated and compared to theoretical predictions when possible. The results showed complex interference patterns resulting from the overlay of different optical phenomena, which can be explained by the presence of a few integrated optical components in the valve. Moreover, studies on the complete frustule in an aqueous medium allow the discussion of its possible photobiological relevance. Furthermore, our results may enable the simple screening of unstudied pennate frustules for photonic applications.

Background: In MR-based radiotherapy (RT), MRI images are co-registered to the planning CT to leverage MR image information for RT planning. Especially in brain stereotactic RT, where typical CTV-PTV margins are 1-2 mm, high registration accuracy is critical. Several factors influence the registration accuracy, including the acquisition setup during MR simulation and the registration methods., Purpose: In this work, the impact of the MRI acquisition setup and registration method was evaluated in the context of brain RT, both geometrically and dosimetrically., Methods and Materials: MRI of 20 brain radiotherapy patients was acquired in two MRI acquisition setups (RT and diagnostic). Three different automatic registration tools provided by three treatment planning systems were used to rigidly register both MRIs and CT in addition to the clinical registration. Segmentation-based evaluation using Hausdorff Distance (HD)/Dice Similarity Coefficient and landmark-based evaluation were used as evaluation metrics. Dose-volume-histograms were evaluated for target volumes and various organs at risks., Results: MRI acquisition in the RT setup provided a similar head extension as compared to the planning CT. The registration method had a more significant influence than the acquisition setup (Wilcoxon signed-rank test, p<0.05). When registering using a less optimal registration method, the RT setup improved the registration accuracy compared to the diagnostic setup (Difference: ΔMHD = 0.16 mm, ΔHD P95 = 0.64 mm, mean Euclidean distance (ΔmEuD) = 2.65 mm). Different registration methods and acquisition setups lead to the variation of the clinical DVH. Acquiring MRI in the RT setup can improve PTV and GTV coverage compared to the diagnostic setup., Conclusions: Both MRI acquisition setup and registration method influence the MRI-CT registration accuracy in brain RT patients geometrically and dosimetrically. MR-simulation in the RT setup assures optimal registration accuracy if automatic registration is impaired, and therefore recommended for brain RT., Competing Interests: Declaration of Competing Interest Universitätsklinikum Erlangen, Strahlenklinik and Siemens Healthineers (Erlangen, Germany) have institutional research contracts not related to this specific work. Christoph Bert and Florian Putz act as speakers in training courses of Siemens Healthineers., (Copyright © 2022. Published by Elsevier GmbH.)

Background: Sacral neuromodulation (SNM) is a common treatment for patients with urinary and faecal incontinence. A close contact of the tined lead electrode with the targeted nerve is likely to improve functional outcome. The aim of this study was to compare the position of the SNM lead in relation to the sacral nerve by comparing different implantation techniques., Methods: This cadaver study was conducted at the Division of Anatomy of Vienna's Medical University in October 2020. We dissected 10 cadavers after bilateral SNM lead implantation (n = 20), using two different standardized implantation techniques. The cadavers were categorized as group A (n = 10), representing the conventional guided implantation group and group B (n = 10), where SNM implantation was conducted with the novel fluoroscopy-guided "H"-technique. The primary goal was to assess the distance between the sacral nerve and the lead placement., Results: The electrodes were inserted at a median angle of 58.5° (46-65°) in group A and 60° (50-65°) in group B, without reaching statistical significance. In 8 cadavers, the lead entered the S3 foramen successfully. The median distance of the lead to the nerve did not show a significant difference between both groups (E0: Group A: 0.0 mm vs. Group B: 0.0 mm, p = 0.969; E1: Group A: 0.0 mm vs. Group B: 0.5 mm p = 0.754; E2: Group A: 2.5 mm vs. Group B: 2.5 mm p = 1.000; E3: Group A: 3.5 mm vs. Group B: 4.0 mm p = 0.675). In 2 cases (20%) of the conventional group A, the lead was misplaced and located at the gluteal muscle. Perforation of the presacral fascia was observed in one lead placement in group A and in two placements in group B., Conclusions: Both standardized implantation techniques may ensure close electrode proximity to the targeted nerve. Misplacement of the electrode was more often observed with the conventional implantation technique., (© 2022. The Author(s).)

Purpose: (1) to improve the comprehension of the topographical position of the talar dome beneath the inferior articular surface of the tibia and, (2) to illustrate the changes of possible access to the articular surface of the talar dome during arthroscopic treatment of talar osteochondral defects in an anatomical model., Methods: Twenty matched pairs (n = 40) of anatomical ankle specimen were used. All specimens were mounted in a standardized fashion, 3-dimensional radiography was performed in 4 defined positions (maximum dorsiflexion, neutral position, noninvasive distraction, and maximum plantarflexion). All radiographs were analyzed and statistically compared., Results: Anterior accessibility was highest in maximum plantarflexion (medial: 49.20 ± 9.86%, lateral: 48.19 ± 8.85%), followed by non-invasive distraction (medial: 33.60 ± 7.96%, lateral: 31.98 ± 8.30%). Neutral position (medial: 19.34 ± 6.90%, lateral: 17.54 ± 6.63%) and dorsiflexion (medial: 15.36 ± 5.03%, lateral: 13.88 ± 4.33%) were not able to significantly increase accessibility. Posterior accessibility was greatest in maximum dorsiflexion (medial: 56.69 ± 9.65%, lateral: 46.82 ± 8.36%), followed by neutral position of the ankle joint (medial: 40.95 ± 8.28%, lateral: 31.06 ± 6.92%). Noninvasive distraction (medial: 31.41 ± 8.18%, lateral: 22.99 ± 7.63%) was still significantly better than plantarflexion (medial: 14.54 ± 5.10%, lateral: 13.89 ± 3.14%) and slightly increased accessibility to the talar dome. Medially, a central area of 5.89 ± 9.76% was accessible by maximum plantarflexion and maximum dorsiflexion from anterior and posterior, respectively, laterally a central blind spot of 4.99 ± 8.61% was detected., Conclusions: From an anatomical point of view, maximum joint positions of the ankle (i.e., plantarflexion and dorsiflexion) allow for better access to the talar dome in anterior and posterior ankle arthroscopy. Noninvasive distraction may increase accessibility in anterior approaches, but has no benefit from posterior., Clinical Relevance: This study provides insight into the morphology of the ankle joint in a standardized laboratory setup and illustrates the influence of different surgically relevant ankle joint positions. The presented data allow for better preoperative planning for the arthroscopic treatment of talar osteochondral defects., (Copyright © 2020 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

The combined resection of skull-infiltrating tumours and immediate cranioplastic reconstruction predominantly relies on freehand-moulded solutions. Techniques that enable this procedure to be performed easily in routine clinical practice would be useful. A cadaveric study was developed in which a new software tool was used to perform single-stage reconstructions with prefabricated implants after the resection of skull-infiltrating pathologies. A novel 3D visualization and interaction framework was developed to create 10 virtual craniotomies in five cadaveric specimens. Polyether ether ketone (PEEK) implants were manufactured according to the bone defects. The image-guided craniotomy was reconstructed with PEEK and compared to polymethyl methacrylate (PMMA). Navigational accuracy and surgical precision were assessed. The PEEK workflow resulted in up to 10-fold shorter reconstruction times than the standard technique. Surgical precision was reflected by the mean 1.1±0.29mm distance between the virtual and real craniotomy, with submillimetre precision in 50%. Assessment of the global offset between virtual and actual craniotomy revealed an average shift of 4.5±3.6mm. The results validated the 'elective single-stage cranioplasty' technique as a state-of-the-art virtual planning method and surgical workflow. This patient-tailored workflow could significantly reduce surgical times compared to the traditional, intraoperative acrylic moulding method and may be an option for the reconstruction of bone defects in the craniofacial region., (Copyright © 2019 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Near-infrared sensitization of monolayer MoS 2 is here achieved via the covalent attachment of a novel heteroleptic nickel bis-dithiolene complex into sulfur vacancies in the MoS 2 structure. Photocurrent action spectroscopy of the sensitized films reveals a discreet contribution from the sensitizer dye centred around 1300 nm (0.95 eV), well below the bandgap of MoS 2 (2.1 eV), corresponding to the excitation of the monoanionic dithiolene complex. A mechanism of conductivity enhancement is proposed based on a photo-induced flattening of the corrugated energy landscape present at sulfur vacancy defect sites within the MoS 2 due to a dipole change within the dye molecule upon photoexcitation. This method of sensitization might be readily extended to other functional molecules that can impart a change to the dielectric environment at the MoS 2 surface under stimulation, thereby extending the breadth of detector applications for MoS 2 and other transition metal dichalcogenides.

Recently, we proposed a [metal|insulator|semiconductor|insulator|metal] (MISIM) photocell, as a novel architecture for high-speed organic photodetectors. The electric polarization in the S layer, induced by modulated light illumination, propagates into the outside circuit as a polarization current through the I layers, without any carrier transfer across the interfaces. In the present work, we examined the MISIM photocells consisting of zinc-phthalocyanine(ZnPc)-C60 bilayers for the S layer and Parylene C for the two I layers, to understand the fundamental aspects of the MISIM photocells, such as current polarity and modulation-frequency dependence. It was found that, in such devices, the current polarity was primarily determined by the polarization in the S layer, which was induced by the donor-acceptor charge-transfer upon illumination. Furthermore, the ON and OFF current, which appeared in the periods of illumination-on and -off, respectively, exhibited significantly different dependence on the modulation frequency. This was well-explained by an imbalance between a quick polarization in the S layer during illumination and its slow relaxation in the dark.

Background: Percutaneous, transverse distal metatarsal osteotomy with K-wire fixation (the Bösch technique) is an established technique for hallux valgus correction. Nevertheless, the risk of damaging the anatomical structures during the operation is unknown., Methods: Forty fresh-frozen anatomical foot specimens with hallux valgus deformity underwent a percutaneous corrective procedure. Specimens of group A (n = 20) were operated by an experienced surgeon while specimens of group B (n = 20) were done by untrained residents., Results: The dorsal cutaneous nerve was injured in 1 of 20 cases in group A and 6 of 20 cases in group B ( P = .037). There was a significant difference in overall complication rate between specimens of group A and group B ( P = .043)., Conclusions: The results show an increased risk of perioperative injury of the dorsal cutaneous branch of the deep peroneal nerve as well as a significant effect of the surgeon's experience on the overall complication rate., Clinical Relevance: Results of this study are highly relevant for all surgeons who perform percutaneous, minimally invasive hallux valgus surgery to avoid damage to the peripheral nerves. In addition, the data suggest an intensive training for surgeons before minimally invasive hallux valgus surgery is performed without supervision.

Purpose: Corneal anesthesia leads to chronic corneal injury. This anatomical study characterizes the donor nerve branches of the supratrochlear and supraorbital nerves used for corneal neurotization., Methods: In 13 non-embalmed cadavers, the supratrochlear and supraorbital nerves were dissected and distances to anatomical landmarks measured. Cross-sections of supratrochlear and supraorbital donor nerves were harvested and histomorphometrically analyzed to assess the number of myelinated axons., Results: The donor axon counts were 3146 ± 1069.9 for the supratrochlear and 1882 ± 903 for the supraorbital nerve distal to the supraorbital notch. The supratrochlear nerve was dissected on the medial upper eyelid 2 cm lateral to the facial midline and the branch of the supraorbital nerve 1 cm medial to the mid-pupillary line., Conclusion: The supraorbital and supratrochlear branches of the trigeminal nerve are potent donor nerves for corneal neurotization in the treatment of neuropathic keratopathy and can be reliably dissected using anatomical landmarks., Competing Interests: The authors have declared that no competing interests exist.

Organic photodetectors offer distinct advantages over their inorganic analogues, most notably through optical transparency and flexibility, yet their figures-of-merit still lag behind those of inorganic devices, and optimization strategies generally encounter a trade-off between device responsivity and bandwidth. Here we propose a novel photodetector architecture in which an organic photoactive semiconductor layer (S) is sandwiched between two thick insulating layers (I) that separate the semiconductor from the metallic contacts (M). In this architecture a differential photocurrent response is generated purely from the polarization of the active layer under illumination. Especially for an asymmetric MISIM design, where one insulating layer is a high-k ionic liquid I IL and the other a low-k polymer dielectric I p , the responsivity/bandwidth trade-off is broken, since the role of the I IL in efficient charge separation is maintained, while the total device capacitance is reduced according to I p . Thus the benefits of single insulating layer differential photodetectors (MISM) using either I IL or I p are combined in a single device. Further improvements in device performance are also demonstrated by decreasing the series resistance of the photoactive layer through semiconductor:metal blending and by operation under strong background light.

Epitranscriptomic events such as adenosine-to-inosine (A-to-I) RNA editing by ADAR can recode mRNAs to translate novel proteins. Editing of the mRNA that encodes actin crosslinking protein Filamin A (FLNA) mediates a Q-to-R transition in the interactive C-terminal region. While FLNA editing is conserved among vertebrates, its physiological function remains unclear. Here, we show that cardiovascular tissues in humans and mice show massive editing and that FLNA RNA is the most prominent substrate. Patient-derived RNA-Seq data demonstrate a significant drop in FLNA editing associated with cardiovascular diseases. Using mice with only impaired FLNA editing, we observed increased vascular contraction and diastolic hypertension accompanied by increased myosin light chain phosphorylation, arterial remodeling, and left ventricular wall thickening, which eventually causes cardiac remodeling and reduced systolic output. These results demonstrate a causal relationship between RNA editing and the development of cardiovascular disease indicating that a single epitranscriptomic RNA modification can maintain cardiovascular health., (© 2018 The Authors. Published under the terms of the CC BY 4.0 license.)

We present a simple and quick system for accurately scoring the developmental progress of mouse embryos harvested on embryonic day 14 (E14.5). Based solely on the external appearance of the maturing forelimb, we provide a convenient way to distinguish six developmental sub-stages. Using a variety of objective morphometric data obtained from the commonly used C57BL/6N mouse strain, we show that these stages correlate precisely with the growth of the entire embryo and its organs. Applying the new staging system to phenotype analyses of E14.5 embryos of 58 embryonic lethal null mutant lines from the DMDD research programme (https://dmdd.org.uk) and its pilot, we show that homozygous mutant embryos are frequently delayed in development. To demonstrate the importance of our staging system for correct phenotype interpretation, we describe stage-specific changes of the palate, heart and gut, and provide examples in which correct diagnosis of malformations relies on correct staging., (© 2017 The Authors Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

The structure and electronic properties of a novel cobalt half sandwich complex of cyclopentadiene (Cp) and diaminonaphthalene (DAnap) [CpCo(DAnap)] are described and compared to the previously reported diaminobenzene derivative [CpCo(DAbnz)] in view of their potential for (opto)electronic device application. Both complexes show stable redox processes, tunable through the diaminoacene ligand, and show strong absorption in the visible region, with additional transitions stretching into the near infrared (NIR). CpCo(DAnap) crystallises with a particularly large unit cell (9301 Å 3 ), comprising 32 molecules, with a gradual rotation over 8 molecules along the long c-axis. In the solid state the balance of the optical transitions in both complexes is reversed, with a suppression of the visible band and an enhancement of the NIR band, attributed to extensive intermolecular electronic interaction. In the case of CpCo(DAnap), highly crystalline thin films could be formed under physical vapor deposition, which show a photocurrent response stretching into the NIR, and p-type semiconductor behavior in field effect transistors with mobility values of the order 1 × 10 -4 cm 2 V -1 s -1 . The device performance is understood through investigation of the morphology of the grown films.

Background: Identifying genes that are essential for mouse embryonic development and survival through term is a powerful and unbiased way to discover possible genetic determinants of human developmental disorders. Characterising the changes in mouse embryos that result from ablation of lethal genes is a necessary first step towards uncovering their role in normal embryonic development and establishing any correlates amongst human congenital abnormalities. Methods: Here we present results gathered to date in the Deciphering the Mechanisms of Developmental Disorders (DMDD) programme, cataloguing the morphological defects identified from comprehensive imaging of 220 homozygous mutant and 114 wild type embryos from 42 lethal and subviable lines, analysed at E14.5. Results: Virtually all mutant embryos show multiple abnormal phenotypes and amongst the 42 lines these affect most organ systems. Within each mutant line, the phenotypes of individual embryos form distinct but overlapping sets. Subcutaneous edema, malformations of the heart or great vessels, abnormalities in forebrain morphology and the musculature of the eyes are all prevalent phenotypes, as is loss or abnormal size of the hypoglossal nerve. Conclusions: Overall, the most striking finding is that no matter how profound the malformation, each phenotype shows highly variable penetrance within a mutant line. These findings have challenging implications for efforts to identify human disease correlates., Competing Interests: No competing interests were disclosed.

Background: Harvesting the submental flap for vascularized lymph node transfer (VLNT) presents a challenging procedure because of, the topographic variation of the submental artery (SA) and the marginal mandible nerve (MMN) and the limited pedicle length for a free tissue transfer. The aim of this study was to evaluate surgical anatomical landmarks and variations of the submental lymph node flap (SLNF)., Methods and Materials: The authors examined the characteristics and landmarks of 18 SLNF in nine fresh cadavers. The diameter, length, and caliber of the SA and its relation to bony anatomic landmarks were measured. In addition, the number of lymph nodes (LNN) was evaluated through dissection and ultrasound., Results: Within the designated SLNF (10 × 5 cm 2 ), the number of LNN was on average 3 ± 0.6, with an average size of 4.5 ± 1.8 mm × 2.9 ± 1.2 mm. Projection of the LNN on the mandible, measured from the gnathion (GT, median-sagittal-plane) toward the gonion (GN, mandibular angle), was at 63.4 ± 5.8 mm (e.g., 65%) of the mandible for the first lymph node (LN), and for the following LNN was at 50.4 ± 7.7 mm (e.g., 52%), 44.0 ± 8.6 mm (e.g., 45%), and 40.50  ±  2.1 mm (e.g., 42%). The MMN consistently crossed the mandible body and the facial artery (FA) from dorso-caudal to ventro-cranial at 72 ± 5.2 mm, e.g., 75% of the mandible's length. Here, the nerve always lay superficial to the FA and was on average 0.96 ± 0.14 mm in diameter. Submental artery was located on average at 64 mm (e.g., 66%) of the mandible, with an average diameter of 1.34 ± 0.2 mm., Conclusion: The submental lymph node flap has a constant vascular supply by the submental artery. Lymph node count is on average three. Lymph nodes are close to the submental artery and its perforators. Marginal mandibular nerve lies superficial to the facial artery and crosses the artery at 75% of the mandible body length (gnathion to gonion = 100%). J. Surg. Oncol. 2017;115:54-59. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

The addition of an insulating layer (I) between one of the metal electrodes (M) and the photoactive semiconducting layer (S) in a standard organic MSM solar cell architecture changes the DC photocurrent response into a strong transient signal. Such a device can, in simple terms, be thought of as a charging voltage source (S) in contact with a charging capacitor (I). The magnitude of the photocurrent signal can be strongly enhanced through the intimate contact of the active layer with the insulating layer, if the various pre-polarizations within the device act synergically. In this study, the effect of the built-in potentials within the device on the polarity and magnitude of the photocurrent response is studied using the well-characterized bulk heterojunction blend system of poly(3-hexylthiophenone):[6,6]-phenyl-C61-butyric acid methyl ester (P3HT:PCBM) as the semiconductor layer, and an ionic liquid as the insulating layer. This study shows that the polarity of the response is not simply determined by the energy level difference of the outer electrodes, but through a delicate interplay of all the energy levels in the device. Furthermore, these observations could be reproduced for devices with a solid-state insulator layer, where possible side-effects of the ionic liquid, such as swelling and doping, could be considered absent.

A novel platform for transient photodetector component screening has been developed whereby an optical fiber tip serves as the counter electrode when placed in a variety of dielectric media, connected to a photoresponsive working electrode. The soft processing conditions allow for ubiquitous photodetection for organic and biological systems.

Channelrhodopsins have become a focus of interest because of their ability to control neural activity by light, used in a technology called optogenetics. The channelrhodopsin in the eukaryote Chlamydomonas reinhardtii (CrChR-1) is a light-gated cation channel responsible for motility changes upon photo-illumination and a member of the membrane-embedded retinal protein family. Recent crystal structure analysis revealed that CrChR-1 has unique extended modules both at its N- and C-termini compared to other microbial retinal proteins. This study reports the first successful expression of a ChR-1 variant in Escherichia coli as a holoprotein: the ChR-1 variant lacking both the N- and C-termini (CrChR-1&#95;82-308). However, compared to ChR-1 having the extended modules (CrChR-1&#95;1-357), truncation of the termini greatly altered the absorption maximum and photochemical properties, including the pKa values of its charged residues around the chromophore, the reaction rates in the photocycle and the photo-induced ion channeling activity. The results of some experiments regarding ion transport activity suggest that CrChR-1&#95;82-308 has a proton channeling activity even in the dark. On the basis of these results, we discuss the structural and functional roles of the N- and C-terminal extended modules in CrChR-1.

A novel planar architecture has been developed for the study of photodetectors utilizing the transient photocurrent response induced by a metal/insulator/semiconductor/metal (MISM) structured device, where the insulator is an ionic liquid (IL-MISM). Using vanadyl 2,3-naphthalocyanine, which absorbs in the communications-relevant near-infrared wavelength region (λ(max,film) ≈ 850 nm), in conjunction with C60 as a bulk heterojunction, the high capacitance of the formed electric double layers at the ionic liquid interfaces yields high charge separation efficiency within the semiconductor layer, and the minimal potential drop in the bulk ionic liquid allows the electrodes to be offset by distances of over 7 mm. Furthermore, the decrease in operational speed with increased electrode separation is beneficial for a clear modeling of the waveform of the photocurrent signal, free from the influence of measurement circuitry. Despite the use of a molecular semiconductor as the active layer in conjunction with a liquid insulating layer, devices with a stability of several days could be achieved, and the operational stability of such devices was shown to be dependent solely on the solubility of the active layer in the ionic liquid, even under atmospheric conditions. Furthermore, the greatly simplified device construction process, which does not rely on transparent electrode materials or direct electrode deposition, provides a highly reproducible platform for the study of the electronic processes within IL-MISM detectors that is largely free from architectural constraints.

We evaluate the usefulness of digital volume data produced with the high-resolution episcopic microscopy (HREM) method for visualizing the three-dimensional (3D) arrangement of components of human skin, and present protocols designed for processing skin biopsies for HREM data generation. A total of 328 biopsies collected from normally appearing skin and from a melanocytic nevus were processed. Cuboidal data volumes with side lengths of ~2×3×6 mm3 and voxel sizes of 1.07×1.07×1.5 µm3 were produced. HREM data fit ideally for visualizing the epidermis at large, and for producing highly detailed volume and surface-rendered 3D representations of the dermal and hypodermal components at a structural level. The architecture of the collagen fiber bundles and the spatial distribution of nevus cells can be easily visualized with volume-rendering algorithms. We conclude that HREM has great potential to serve as a routine tool for researching and diagnosing skin pathologies.

Ion-transporting rhodopsins are widely utilized as optogenetic tools both for light-induced neural activation and silencing. The most studied representative is Bacteriorhodopsin (BR), which absorbs green/red light (∼570 nm) and functions as a proton pump. Upon photoexcitation, BR induces a hyperpolarization across the membrane, which, if incorporated into a nerve cell, results in its neural silencing. In this study, we show that several residues around the retinal chromophore, which are completely conserved among BR homologs from the archaea, are involved in the spectral tuning in a BR homolog (HwBR) and that the combination mutation causes a large spectral blue shift (λmax = 498 nm) while preserving the robust pumping activity. Quantum mechanics/molecular mechanics calculations revealed that, compared with the wild type, the β-ionone ring of the chromophore in the mutant is rotated ∼130° because of the lack of steric hindrance between the methyl groups of the retinal and the mutated residues, resulting in the breakage of the π conjugation system on the polyene chain of the retinal. By the same mutations, similar spectral blue shifts are also observed in another BR homolog, archearhodopsin-3 (also called Arch). The color variant of archearhodopsin-3 could be successfully expressed in the neural cells of Caenorhabditis elegans, and illumination with blue light (500 nm) led to the effective locomotory paralysis of the worms. Thus, we successfully produced a blue-shifted proton pump for neural silencing.

Rhodopsin contains retinal as the chromophore within seven transmembrane helices. Recently, we found a unique rhodopsin (middle rhodopsin, MR), which is evolutionarily located between the well-studied bacteriorhodopsin and sensory rhodopsin II, and which accommodates three retinal isomers in its ground state (the all-trans, the 13-cis, and, uniquely, the 11-cis isomers). In this study, we investigated structural changes of both the protein moiety and the retinal chromophore during photocycles of MR by time-resolved Fourier-transform infrared spectroscopy. Three photointermediates with decay time constants of 95 μs, 0.9 ms, and >~10 ms were identified by the global exponential fitting analysis. The first and third intermediates were attributed to the all-trans photocycle, in accordance with recently published results, whereas the second intermediate was likely one that was spectroscopically silent in the visible region and that was formed between the first and third states or resulted from the activation of the 13-cis isomer. By comparing light-induced difference spectra with various isotope labels in either the retinal or the protein moiety, we concluded that a β-sheet structure in the hydrophilic part was significantly altered during the all-trans photocycle of MR, which may involve an active state of the protein. This feature is characteristic of MR among microbial (type-1) rhodopsins.

In nature, organisms are subjected to a variety of environmental stimuli to which they respond and adapt. They can show avoidance or attractive behaviors away from or toward such stimuli in order to survive in the various environments in which they live. One such stimuli is light, to which, for example, the receptor sensory rhodopsin I (SRI) has been found to respond by regulating both negative and positive phototaxis in, e.g., the archaeon Halobacterium salinarum. Interestingly, to date, all organisms having SRI-like proteins live in highly halophilic environments, suggesting that salt significantly influences the properties of SRIs. Taking advantage of the discovery of the highly stable SRI homologue from Salinibacter ruber (SrSRI), which maintains its color even in the absence of salt, the importance of the chloride ion for the color tuning and for the slow M-decay, which is thought to be essential for the phototaxis function of SRIs, has been reported previously [Suzuki, D., et al. (2009) J. Mol. Biol.392, 48-62]. Here the effects of the anion binding on the structure and structural changes of SRI during its photocycle are investigated by means of Fourier transform infrared (FTIR) spectroscopy and electrochemical experiments. Our results reveal that, among other things, the structural change and proton movement of a characteristic amino acid residue, Asp102 in SrSRI, is suppressed by the binding of an anion in its vicinity, both in the K- and M-intermediate. The presence of this anion also effects the extent of chromophore distrotion, and tentative results indicate an influence on the number and/or properties of internal water molecules. In addition, a photoinduced proton transfer could only be observed in the absence of the bound anion. Possible proton movement pathways, including the residues Asp102 and the putative Cl binding site His131, are discussed. In conclusion, the results show that the anion binding to SRI is not only important for the color tuning, and for controlling the photocycle kinetics, but also induces some structural changes which facilitate the observed properties.

Photoactive proteins with cognate chromophores are widespread in organisms, and function as light-energy converters or receptors for light-signal transduction. Rhodopsins, which have retinal (vitamin A aldehyde) as their chromophore within their seven transmembrane α-helices, are classified into two groups, microbial (type-1) and animal (type-2) rhodopsins. In general, light absorption by type-1 or type-2 rhodopsins triggers a trans-cis or cis-trans isomerization of the retinal, respectively, initiating their photochemical reactions. Recently, we found a new microbial rhodopsin (middle rhodopsin, MR), binding three types of retinal isomers in its original state: all-trans, 13-cis, and 11-cis. Here, we identified the absolute absorption spectra of MR by a combination of high performance liquid chromatography (HPLC) and UV-vis spectroscopy under varying light conditions. The absorption maxima of MR with all-trans, 13-cis, or 11-cis retinal are located at 485, 479, and 495 nm, respectively. Their photocycles were analyzed by time-resolved laser spectroscopy using various laser wavelengths. In conclusion, we propose that the photocycles of MR are MR(trans) → MR(K):lifetime = 93 μs → MR(M):lifetime = 12 ms → MR, MR(13-cis) → MR(O-like):lifetime = 5.1 ms → MR, and MR(11-cis) → MR(K-like):lifetime = 8.2 μs → MR, respectively. Thus, we demonstrate that a single photoactive protein drives three independent photochemical reactions.

Organisms sense and respond to environmental stimuli through membrane-embedded receptors and transducers. Sensory rhodopsin I (SRI) and sensory rhodopsin II (SRII) are the photoreceptors for the positive and negative phototaxis in microorganisms, respectively. They form signaling complexes in the membrane with their cognate transducer proteins, HtrI and HtrII, and these SRI-HtrI and SRII-HtrII complexes transmit a light signal through their cytoplasmic sensory signaling system, inducing opposite effects (i.e., the inactivation or activation of the kinase CheA). Here we found, by using Fourier transformed infrared spectroscopy, that a conserved residue, Asp102 in Salinibacter SRI (SrSRI), which is located close to the β-ionone ring of the retinal chromophore, is deprotonated upon formation of the active M-intermediate. Furthermore, the D102E mutant of SrSRI affects the structure and/or structural changes of Cys130. This mutant shows a large spectral shift and is comparably unstable, especially in the absence of Cl(-). These phenomena have not been observed in the wild-type, or the N105Q and N105D mutants of Natronomonas pharaonis SRII (NpSRII), indicating differences in the structure and structural changes between SrSRI and NpSRII around the β-ionone ring. These differences could also be supported by the measurements of the reactivity with the water-soluble reagent azide. On the basis of these results, we discuss the structure and structural changes around the retinal chromophore in SrSRI.

After contact with water, surfactant lamellar phases (L(α)) can show spectacular interface instabilities: multibilayer tubules, so-called myelins, grow from the L(α)/water interface into the water. We have studied the shape, size, and growth of myelins in aqueous solutions of the nonionic surfactant C(12)E(3) (triethylene glycol monododecyl ether) during dissolution. We used a combination of different imaging techniques: optical microscopy providing 2-D projections of the sample and confocal microscopy offering a complete 3-D reconstruction. These techniques provide quantitative information on the shape and growth of myelins, such as their width, length, and depth profile as a function of time. The growth rate of myelins, characterized by a swelling or diffusion coefficient, was found to increase with surfactant mass fraction and, seemingly, with sample thickness. We demonstrate that myelin creaming due to buoyancy can explain the apparent dependence on sample thickness. Our experiments furthermore suggest that myelin growth is controlled by an interplay between the water mobility in the lamellar phase and the osmotic pressure difference between the lamellar phase and the contacting water.