Incorporating a Polyethyleneglycol Linker to Enhance the Hydrophilicity of Mitochondria-Targeted Triphenylphosphonium Constructs.

The targeting of bioactive molecules and probes to mitochondria can be achieved by coupling to the lipophilic triphenyl phosphonium (TPP) cation, which accumulates several hundred-fold within mitochondria in response to the mitochondrial membrane potential (Δψm ). Typically, a simple alkane links the TPP to its "cargo", increasing overall hydrophobicity. As it would be beneficial to enhance the water solubility of mitochondria-targeted compounds we explored the effects of replacing the alkyl linker with a polyethylene glycol (PEG). We found that the use of PEG led to compounds that were readily taken up by isolated mitochondria and by mitochondria inside cells. Within mitochondria the PEG linker greatly decreased adsorption of the TPP constructs to the matrix-facing face of the mitochondrial inner membrane. These findings will allow the distribution of mitochondria-targeted TPP compounds within mitochondria to be fine-tuned.

Parker Solar Probe Imaging of the Night Side of Venus.

We present images of Venus from the Wide-Field Imager for Parker Solar Probe (WISPR) telescope on board the Parker Solar Probe (PSP) spacecraft, obtained during PSP's third and fourth flybys of Venus on 2020 July 11 and 2021 February 20, respectively. Thermal emission from the surface is observed on the night side, representing the shortest wavelength observations of this emission ever, the first detection of the Venusian surface by an optical telescope observing below 0.8 µm. Consistent with previous observations at 1 µm, the cooler highland areas are fainter than the surrounding lowlands. The irradiances measured by WISPR are consistent with model predictions assuming a surface temperature of T = 735 K. In addition to the thermal emission, the WISPR images also show bright nightglow emission at the limb, and we compare the WISPR intensities with previous spectroscopic measurements of the molecular oxygen nightglow lines from Venus Express.

Perspectives on modes of labour and delivery after different modalities of surgery for bowel endometriosis.

Bowel or intestinal endometriosis is estimated to affect 5-37% of women with deep infiltrative endometriosis (DIE), especially in the rectum and recto-sigmoid junction. However, there are no current guidelines or consensus regarding safest mode of delivery in pregnant women after different surgical interventions for bowel/intestinal endometriosis. From October 2019 to February 2020, we conducted an online survey of members of the British Society for Gynaecological Endoscopy (BSGE). These included questions on what gynaecologist members would recommend as modes of delivery in women who had different surgical modalities for bowel endometriosis, and the particular factors that influence such recommendations. Analysis of data was performed using SPSS for Windows (V9) software package. One hundred and two members of BSGE completed the survey (61.76% of BSGE gynaecologist members). Only 30.39% of respondents counsel women, pre-operatively, about possible effects of surgical treatment of bowel endometriosis on their subsequent mode of delivery. Our survey highlights wide variation in practice that currently exists. Around 70% of clinicians are not counselling patients regarding delivery options pre-surgery despite almost one-third recommending planned caesarean section if the vagina is opened. Further studies are required to stratify the risk factors for such patients when attempting vaginal delivery or caesarean section.IMPACT STATEMENTWhat is already known on this subject? Treatment of colorectal endometriosis consists of rectal shaving, discoid resection or segmental colorectal resection. However, the relationship between different surgical modalities for bowel endometriosis and the subsequent safe mode of labour and delivery remains unclear.What do the results of this study add? No study has been published that specifically looked at the particular course and outcome of labour and delivery after each of these bowel surgeries; rectal shaving, disc excision, or segmental colorectal resection. Our study highlights the wide variations in practice that currently exists. Despite around 70% of clinicians not counselling women regarding delivery options pre-surgery, almost one-third would recommend a planned caesarean section if the vagina is opened.What are the implications of these findings for clinical practice and/or further research? This study suggests that risk factors should be stratified for such patients when attempting a vaginal delivery or undergoing a caesarean section. Guidance from the ESGE and/or BSGE would be useful to aid in the counselling and informed consent of such patients.

Expansion microscopy: A powerful nanoscale imaging tool for neuroscientists.

One of the biggest unsolved questions in neuroscience is how molecules and neuronal circuitry create behaviors, and how their misregulation or dysfunction results in neurological disease. Light microscopy is a vital tool for the study of neural molecules and circuits. However, the fundamental optical diffraction limit precludes the use of conventional light microscopy for sufficient characterization of critical signaling compartments and nanoscopic organizations of synapse-associated molecules. We have witnessed rapid development of super-resolution microscopy methods that circumvent the resolution limit by controlling the number of emitting molecules in specific imaging volumes and allow highly resolved imaging in the 10-100 nm range. Most recently, Expansion Microscopy (ExM) emerged as an alternative solution to overcome the diffraction limit by physically magnifying biological specimens, including nervous systems. Here, we discuss how ExM works in general and currently available ExM methods. We then review ExM imaging in a wide range of nervous systems, including Caenorhabditis elegans, Drosophila, zebrafish, mouse, and human, and their applications to synaptic imaging, neuronal tracing, and the study of neurological disease. Finally, we provide our prospects for expansion microscopy as a powerful nanoscale imaging tool in the neurosciences.

The effect of the angle of acuteness of additive manufactured models and the direction of printing on the dimensional fidelity: clinical implications.

The influence of the acuteness of the model angle and the direction of printing was investigated on different three-dimensional (3D) printers to understand the fidelity of 3D printing. A Polyjet printer and two fused deposition modeling printers were used in the present study. Computer-aided design (CAD) models were designed in the form of a triangular prism with a height of 15 mm and with varying angles of 60°, 45°, 30°, 20°, 10°, and 5°. From the CAD designs, additive manufacturing (AM) models were printed in three different directions by each of the three printers. To investigate the global fidelity of the 3D printers, the height and surface outlines of the AM model cross sections were measured. The fidelity of the AM models with increasingly acute angles was not accurately reproduced when 3D printed, and the surface outlines of the AM model cross sections were different in each direction of printing for each device. Printing technology and printing direction need to be considered if accurate reproduction of acute angles in fine AM structures in medical models is a necessity.

Does formal education and training of staff reduce the operation rate for fractures of the distal radius?

BACKGROUND: Fractures of the distal radius are one of the most common extremity fractures, and operation rates are increasing. Staff within our unit felt that formal teaching, particularly of new medical staff, with regards to fracture reduction and appropriate cast application could result in a reduction in operation rates. METHODS: Retrospective data was extracted from FORD (Fracture Outcome and Research Database), including: number of fractures, number of fractures undergoing ORIF, fracture configuration, patient demographics, and mechanism of injury. All patients undergoing ORIF had their radiographs assessed by two separate reviewers. Information regarding adequate fracture reduction, adequate cast application (using Gap Index), and appropriate plaster cast moulding was recorded. Formal teaching was then given to the next group of medical staff rotating through the unit, and the same data was collected prospectively for that six-month period. Exclusion criteria included bilateral injuries, and polytrauma patients. RESULTS: A total of 1623 distal radial fractures were treated in our unit over the 12-month period, with 71 undergoing ORIF in the first 6 months and 39 in the second 6 months, this was statistically significant (p = 0.0009). Our study found that formal teaching and education significantly reduced the operation rate for distal radial fractures. This effect was most significant for extra-articular, dorsally angulated fractures of the distal radius. CONCLUSION: Our study proves that just 1 h of basic training at the beginning of an attachment can have significant benefits to both the unit and, more importantly, the patients.

Universal Molecular Retention with 11-Fold Expansion Microscopy.

The nanoscale imaging of biological specimens can improve the understanding of disease pathogenesis. In recent years, expansion microscopy (ExM) has been demonstrated to be an effective and low-cost alternative to optical super-resolution microscopy. However, it has been limited by the need for specific and often custom anchoring agents to retain different biomolecule classes within the gel and by difficulties with expanding standard clinical sample formats, such as formalin-fixed paraffin-embedded tissue, especially if larger expansion factors or preserved protein epitopes are desired. Here, we describe Magnify, a new ExM method for robust expansion up to 11-fold in a wide array of tissue types. By using methacrolein as the chemical anchor between the tissue and gel, Magnify retains multiple biomolecules, such as proteins, lipids, and nucleic acids, within the gel, thus allowing the broad nanoscale imaging of tissues on conventional optical microscopes. This protocol describes best practices to ensure robust and crack-free tissue expansion, as well as tips for handling and imaging highly expanded gels.

Current concepts in the management of "Terrible Triad" injuries of the elbow.

Terrible triad injuries of the elbow are complex injuries which can result in long term complications and significant disability. They must be identified correctly, and managed appropriately in order to maximise functional outcomes. A clear understanding of the bony and ligamentous anatomy is essential to plan appropriate surgical reconstruction to provide elbow stability. Urgent reduction of the elbow, followed by 3-dimensional imaging and surgical repair or replacement of the injured structures is the mainstay of treatment in the majority of cases. This review presents a summary of the relevant anatomy and the evidence for the management of these complex injuries.

Magnify is a universal molecular anchoring strategy for expansion microscopy.

Expansion microscopy enables nanoimaging with conventional microscopes by physically and isotropically magnifying preserved biological specimens embedded in a crosslinked water-swellable hydrogel. Current expansion microscopy protocols require prior treatment with reactive anchoring chemicals to link specific labels and biomolecule classes to the gel. We describe a strategy called Magnify, which uses a mechanically sturdy gel that retains nucleic acids, proteins and lipids without the need for a separate anchoring step. Magnify expands biological specimens up to 11 times and facilitates imaging of cells and tissues with effectively around 25-nm resolution using a diffraction-limited objective lens of about 280 nm on conventional optical microscopes or with around 15 nm effective resolution if combined with super-resolution optical fluctuation imaging. We demonstrate Magnify on a broad range of biological specimens, providing insight into nanoscopic subcellular structures, including synaptic proteins from mouse brain, podocyte foot processes in formalin-fixed paraffin-embedded human kidney and defects in cilia and basal bodies in drug-treated human lung organoids.

MicroMagnify: a multiplexed expansion microscopy method for pathogens and infected tissues.

Super-resolution optical imaging tools are crucial in microbiology to understand the complex structures and behavior of microorganisms such as bacteria, fungi, and viruses. However, the capabilities of these tools, particularly when it comes to imaging pathogens and infected tissues, remain limited. We developed µMagnify, a nanoscale multiplexed imaging method for pathogens and infected tissues that are derived from an expansion microscopy technique with a universal biomolecular anchor. We formulated an enzyme cocktail specifically designed for robust cell wall digestion and expansion of microbial cells without distortion while efficiently retaining biomolecules suitable for high-plex fluorescence imaging with nanoscale precision. Additionally, we developed an associated virtual reality tool to facilitate the visualization and navigation of complex three-dimensional images generated by this method in an immersive environment allowing collaborative exploration among researchers around the world. µMagnify is a valuable imaging platform for studying how microbes interact with their host systems and enables development of new diagnosis strategies against infectious diseases.

The Photochemical Mediated Ring Contraction of 4H-1,2,6-Thiadiazines To Afford 1,2,5-Thiadiazol-3(2H)-one 1-Oxides.

1,2,6-Thiadiazines treated with visible light and 3O2 under ambient conditions are converted into difficult-to-access 1,2,5-thiadiazole 1-oxides (35 examples, yields of 39-100%). Experimental and theoretical studies reveal that 1,2,6-thiadiazines act as triplet photosensitizers that produce 1O2 and then undergo a chemoselective [3 + 2] cycloaddition to give an endoperoxide that ring contracts with selective carbon atom excision and complete atom economy. The reaction was optimized under both batch and continuous-flow conditions and is also efficient in green solvents.

MicroMagnify: A Multiplexed Expansion Microscopy Method for Pathogens and Infected Tissues.

Super-resolution optical imaging tools are crucial in microbiology to understand the complex structures and behavior of microorganisms such as bacteria, fungi, and viruses. However, the capabilities of these tools, particularly when it comes to imaging pathogens and infected tissues, remain limited. MicroMagnify (µMagnify) is developed, a nanoscale multiplexed imaging method for pathogens and infected tissues that are derived from an expansion microscopy technique with a universal biomolecular anchor. The combination of heat denaturation and enzyme cocktails essential is found for robust cell wall digestion and expansion of microbial cells and infected tissues without distortion. µMagnify efficiently retains biomolecules suitable for high-plex fluorescence imaging with nanoscale precision. It demonstrates up to eightfold expansion with µMagnify on a broad range of pathogen-containing specimens, including bacterial and fungal biofilms, infected culture cells, fungus-infected mouse tone, and formalin-fixed paraffin-embedded human cornea infected by various pathogens. Additionally, an associated virtual reality tool is developed to facilitate the visualization and navigation of complex 3D images generated by this method in an immersive environment allowing collaborative exploration among researchers worldwide. µMagnify is a valuable imaging platform for studying how microbes interact with their host systems and enables the development of new diagnosis strategies against infectious diseases.

Desire for control and the integrated motivational-volitional model of suicidal behavior: Results from a pilot investigation of adults in the United Kingdom.

BACKGROUND: Suicidal behavior remains a pressing problem in the United Kingdom. Continued theory development is a critical step toward designing effective prevention. AIMS: The present study tested a novel element to suicide theory, the Desire for Control, for its direct and moderating roles within the Integrated Motivational-Volitional (IMV) Model of Suicidal Behavior. METHOD: An online-administered cross-sectional suicide risk survey study (n = 116) was conducted among adults living in the United Kingdom. RESULTS: Mean suicidal ideation scores were in the non-clinical range. DOC Leadership and Destiny Control were associated with good mental health. DOC Decision Avoidance was associated with poor mental health. DOC Decision Avoidance also acted as a motivational moderator in which the entrapment-suicidal thinking link was worse among those high in decisional avoidance. CONCLUSION: DOC represents a novel, valuable addition to suicide theory and may inform suicide-specific psychotherapeutic intervention. Additional research is needed to full understand the role of DOC and its factor structures in the IMV.

Super-Resolution Vibrational Imaging Using Expansion Stimulated Raman Scattering Microscopy.

Stimulated Raman scattering (SRS) microscopy is an emerging technology that provides high chemical specificity for endogenous biomolecules and can circumvent common constraints of fluorescence microscopy including limited capabilities to probe small biomolecules and difficulty resolving many colors simultaneously. However, the resolution of SRS microscopy remains governed by the diffraction limit. To overcome this, a new technique called molecule anchorable gel-enabled nanoscale Imaging of Fluorescence and stimulated Raman scattering microscopy (MAGNIFIERS) that integrates SRS microscopy with expansion microscopy (ExM) is described. MAGNIFIERS offers chemical-specific nanoscale imaging with sub-50 nm resolution and has scalable multiplexity when combined with multiplex Raman probes and fluorescent labels. MAGNIFIERS is used to visualize nanoscale features in a label-free manner with CH vibration of proteins, lipids, and DNA in a broad range of biological specimens, from mouse brain, liver, and kidney to human lung organoid. In addition, MAGNIFIERS is applied to track nanoscale features of protein synthesis in protein aggregates using metabolic labeling of small metabolites. Finally, MAGNIFIERS is used to demonstrate 8-color nanoscale imaging in an expanded mouse brain section. Overall, MAGNIFIERS is a valuable platform for super-resolution label-free chemical imaging, high-resolution metabolic imaging, and highly multiplexed nanoscale imaging, thus bringing SRS to nanoscopy.

Thermal Transfer on Splinted Implants During Diode Laser Irradiation In Vitro.

Objective: Laser irradiation is being used for treatment of peri-implantitis. Therefore, this study aimed to assess the heat transfer from laser irradiation on an implant-supported, metal-ceramic fixed prosthesis in vitro. Materials and methods: Two titanium implants were placed in artificial type I bone, and after abutment connection, a bridge was fabricated and cemented. A peri-implant 3-wall defect was created around one of the implants. Thermocouples were placed at coronal (T1/T2) and apical (T3/T4) positions of both implants, and the T5 thermocouple was placed in the pontic. An identical setup was created in the type IV artificial bone. Diode laser irradiation (2 W, noninitiated tips, 320-µm fiber, and noncontact) was performed for 60 sec on each experimental model. This experiment was performed separately with 810- and 980-nm lasers for pulsed and continuous modes. ΔT based on the baseline was recorded during irradiation. Statistical analysis was performed with repeated analysis of variance. Results: Across all experimental models, the recorded ΔT (°) values in T2, T4, and T5 at 10, 30, and 60 sec were significantly less than 10°C (p < 0.001) for both types of bones. For both types of bones, there was a statistically significant ΔT greater than 10°C (p < 0.001) for continuous and pulsed 980-nm irradiation and continuous 810-nm diode laser irradiation after 60 sec. For both 810- and 980-nm lasers, there was a statistically significant ΔT greater than 10°C (p < 0.001) for type I and IV bones under irradiation and only for the type I bone model under pulsed irradiation after 60 sec. Conclusions: Within the limitations of this study, 810- and 980-nm lasers on splinted implants placed in vitro may increase the temperature on adjacent splinted implants due to material conductivity and splinting. Clinicians are advised to keep the temperature lower than the critical threshold following recommended power settings to avoid excessive heat and control complications due to overheating.

Amino acid-derived bisphenolate palladium complexes as C-C coupling catalysts.

A series of amine bisphenol (ABP) pro-ligands featuring amino acid ester pendant arms were prepared. Optimisation of the synthetic method allowed the facile incorporation of naturally occurring, chiral amino acids into the ABP scaffold with minimal racemisation. Reaction of the pro-ligands (LH2) with Pd(OAc)2, in the presence of amines, led to the formation of complexes with an unprecedented pincer-like O,N,O coordination mode around the PdII centre. The complexations in the presence of trialkylamines (NR3) afforded a mixture of LPdNR3 and LPdNHR2 species. The latter was shown to form via an ambient-temperature C-N cleavage involving unstable Pd(OAc)2(NHR2)2 intermediates. Using pyridine as base eliminated this dealkylation and resulted in the exclusive formation of LPd(py) complexes in high yields. In total, seven novel PdII ABP complexes were prepared, exhibiting distorted square-planar geometries with the asymmetric ligand moieties orientated towards the metal centre. The air- and moisture-stable LPd(py) complexes were successfully employed as catalysts in two types of C-C coupling reactions. The Suzuki-Miyaura coupling of 4'-bromoacetophenone and phenylboronic acid reached high yields (up to 81%), while a scope of further alkyl bromides was also efficiently converted using low catalyst loadings (1 mol%) and mild temperatures (40 °C). Furthermore, a Pd-pyridine complex achieved high activity in the Mizoroki-Heck coupling of styrene and 4'-bromoacetophenone.

Three dimensions of desirability of control: divergent relations with psychological and physical well-being.

Objective: To examine unique relations of three distinct dimensions of desirability of control with psychological and physical well-being and coping. Design: Study 1 (n = 122) surveyed undergraduates' response to everyday stressors, and Study 2 (n = 105) examined undergraduates' adjustment to the 11 September 2001 terrorist attacks at 1 and 3 months post-attack. Main outcome measures included psychological distress, perceived stress, rumination, health behaviors, alcohol use and active vs. avoidant coping. Study 1 Results: Self- and other-control were associated with active coping, whereas relinquishing control was linked with avoidant coping. Only relinquishing control was uniquely linked with outcomes, including worse psychological and physical well-being and alcohol use; avoidant coping mediated relations to psychological well-being. Study 2 Results: Again, self-control was associated with active coping whereas relinquishing control was linked with avoidant coping. Self-control was associated with enhanced psychological well-being at T1 and increases in well-being over time; by contrast, relinquishing control was associated with worse T1 psychological well-being, which was mediated by avoidant coping. Conclusion: This is the first study to examine the unique contribution of each DOC dimension with outcomes. Self-control and relinquishing control showed divergent relations to psychological well-being, mediated by different coping pathways.