Intra-pocket ultrasound-guided axillary vein puncture vs. cephalic vein cutdown for cardiac electronic device implantation: the ACCESS trial.

BACKGROUND AND AIMS: Intra-pocket ultrasound-guided axillary vein puncture (IPUS-AVP) for venous access in implantation of transvenous cardiac implantable electronic devices (CIED) is uncommon due to the lack of clinical evidence supporting this technique. This study investigated the efficacy and early complications of IPUS-AVP compared to the standard method using cephalic vein cutdown (CVC) for CIED implantation. METHODS: ACCESS was an investigator-led, interventional, randomized (1:1 ratio), monocentric, controlled superiority trial. A total of 200 patients undergoing CIED implantation were randomized to IPUS-AVP (n = 101) or CVC (n = 99) as a first assigned route. The primary endpoint was the success rate of insertion of all leads using the first assigned venous access technique. The secondary endpoints were time to venous access, total procedure duration, fluoroscopy time, X-ray exposure, and complications. Complications were monitored during a follow-up period of three months after procedure. RESULTS: IPUS-AVP was significantly superior to CVC for the primary endpoint with 100 (99.0%) vs. 86 (86.9%) procedural successes (P = .001). Cephalic vein cutdown followed by subclavian vein puncture was successful in a total of 95 (96.0%) patients, P = .21 vs. IPUS-AVP. All secondary endpoints were also significantly improved in the IPUS-AVP group with reduction in time to venous access [3.4 vs. 10.6 min, geometric mean ratio (GMR) 0.32 (95% confidence interval, CI, 0.28-0.36), P < .001], total procedure duration [33.8 vs. 46.9 min, GMR 0.72 (95% CI 0.67-0.78), P < .001], fluoroscopy time [2.4 vs. 3.3 min, GMR 0.74 (95% CI 0.63-0.86), P < .001], and X-ray exposure [1083 vs. 1423 mGy.cm², GMR 0.76 (95% CI 0.62-0.93), P = .009]. There was no significant difference in complication rates between groups (P = .68). CONCLUSIONS: IPUS-AVP is superior to CVC in terms of success rate, time to venous access, procedure duration, and radiation exposure. Complication rates were similar between the two groups. Intra-pocket ultrasound-guided axillary vein puncture should be a recommended venous access technique for CIED implantation.

Hyperbaric oxygen therapy for late radiation tissue injury.

BACKGROUND: This is the third update of the original Cochrane Review published in July 2005 and updated previously in 2012 and 2016. Cancer is a significant global health issue. Radiotherapy is a treatment modality for many malignancies, and about 50% of people having radiotherapy will be long-term survivors. Some will experience late radiation tissue injury (LRTI), developing months or years following radiotherapy. Hyperbaric oxygen therapy (HBOT) has been suggested as a treatment for LRTI based on the ability to improve the blood supply to these tissues. It is postulated that HBOT may result in both healing of tissues and the prevention of complications following surgery and radiotherapy. OBJECTIVES: To evaluate the benefits and harms of hyperbaric oxygen therapy (HBOT) for treating or preventing late radiation tissue injury (LRTI) compared to regimens that excluded HBOT. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 24 January 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. survival from time of randomisation to death from any cause; 2. complete or substantial resolution of clinical problem; 3. site-specific outcomes; and 4. ADVERSE EVENTS: Our secondary outcomes were 5. resolution of pain; 6. improvement in quality of life, function, or both; and 7. site-specific outcomes. We used GRADE to assess certainty of evidence. MAIN RESULTS: Eighteen studies contributed to this review (1071 participants) with publications ranging from 1985 to 2022. We added four new studies to this updated review and evidence for the treatment of radiation proctitis, radiation cystitis, and the prevention and treatment of osteoradionecrosis (ORN). HBOT may not prevent death at one year (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.47 to 1.83; I2 = 0%; 3 RCTs, 166 participants; low-certainty evidence). There is some evidence that HBOT may result in complete resolution or provide significant improvement of LRTI (RR 1.39, 95% CI 1.02 to 1.89; I2 = 64%; 5 RCTs, 468 participants; low-certainty evidence) and HBOT may result in a large reduction in wound dehiscence following head and neck soft tissue surgery (RR 0.24, 95% CI 0.06 to 0.94; I2 = 70%; 2 RCTs, 264 participants; low-certainty evidence). In addition, pain scores in ORN improve slightly after HBOT at 12 months (mean difference (MD) -10.72, 95% CI -18.97 to -2.47; I2 = 40%; 2 RCTs, 157 participants; moderate-certainty evidence). Regarding adverse events, HBOT results in a higher risk of a reduction in visual acuity (RR 4.03, 95% CI 1.65 to 9.84; 5 RCTs, 438 participants; high-certainty evidence). There was a risk of ear barotrauma in people receiving HBOT when no sham pressurisation was used for the control group (RR 9.08, 95% CI 2.21 to 37.26; I2 = 0%; 4 RCTs, 357 participants; high-certainty evidence), but no such increase when a sham pressurisation was employed (RR 1.07, 95% CI 0.52 to 2.21; I2 = 74%; 2 RCTs, 158 participants; high-certainty evidence). AUTHORS' CONCLUSIONS: These small studies suggest that for people with LRTI affecting tissues of the head, neck, bladder and rectum, HBOT may be associated with improved outcomes (low- to moderate-certainty evidence). HBOT may also result in a reduced risk of wound dehiscence and a modest reduction in pain following head and neck irradiation. However, HBOT is unlikely to influence the risk of death in the short term. HBOT also carries a risk of adverse events, including an increased risk of a reduction in visual acuity (usually temporary) and of ear barotrauma on compression. Hence, the application of HBOT to selected participants may be justified. The small number of studies and participants, and the methodological and reporting inadequacies of some of the primary studies included in this review demand a cautious interpretation. More information is required on the subset of disease severity and tissue type affected that is most likely to benefit from this therapy, the time for which we can expect any benefits to persist and the most appropriate oxygen dose. Further research is required to establish the optimum participant selection and timing of any therapy. An economic evaluation should also be undertaken.

Clogging of a Rectangular Slit by a Spherical Soft Particle.

The capture of a soft spherical particle in a rectangular slit leads to a nonmonotonic pressure-flow rate relation at low Reynolds number. Simulations reveal that the flow induced deformations of the trapped particle focus the streamlines and pressure drop to a small region. This increases the resistance to flow by several orders of magnitude as the driving pressure is increased. As a result, two regimes are observed in experiments and simulations: a flow-dominated regime for small particle deformations, where flow rate increases with pressure, and an elastic-dominated regime in which solid deformations block the flow.

Assessment of HDR brachytherapy-replicating prostate radiotherapy planning for tomotherapy, cyberknife and VMAT.

A dosimetric study was undertaken to assess the ability of Cyberknife (CK), Volumetric Modulated Arc Therapy (VMAT), and TomoTherapy (Tomo) to generate treatment plans that mimic the dosimetry of high dose-rate brachytherapy (HDR BT) for prostate cancer. The project aimed to assess the potential of using stereotactic body radiotherapy (SBRT) for boost treatment of high-risk prostate cancer patients where HDR BT in combination with conformal external beam radiotherapy (EBRT) is the standard of care. The datasets of 6 prostate patients previously treated with HDR BT were collated. VMAT, CK, and TomoTherapy treatment plans were generated for each dataset using the target and organ-at-risk structures as defined by the Radiation Oncologist during the HDR BT treatment process. The HDR BT plan isodoses were also converted into planning structures to assist the other modalities to achieve a HDR BT-like dose distribution. CK plans were created using both the iris collimator (IC) and a multileaf collimator (MLC). Comparison of the techniques was made based on dose-volume indices. Each plan was created at centres experienced using the respective treatment planning systems (TPS). Planning target volume (PTV V100%), i.e., the volume of the planning target volume (PTV) receiving 100% of the relative dose, in VMAT and TomoTherapy SBRT plans was higher than HDR BT plans. PTV V150% and V200%, i.e., volume of the PTV receiving 150% and 200% of the relative dose, were approached on all the CK MLC and TomoTherapy SBRT plans. However, it is not presently achievable for "virtual brachytherapy" SBRT to replicate the same high intraprostatic doses as HDR BT while meeting the constraints on the organs-at-risk (OARs). Half of the CK IC plans achieved PTV V150% but this was at the expense of high rectal dose. TomoTherapy and CK MLC plans achieved PTV V150% and V200% but the bladder dose was higher compared to CK IC plans. VMAT exhibited excellent PTV coverage based on V100 and OAR sparing, but without any ability to achieve the high intra-prostatic doses of HDR (V150% and V200%). SBRT techniques can be used to deliver hypofractionated radiotherapy to the PTV V100%. Based on the comparison of "physical" dose distributions, SBRT cannot presently achieve the same high intraprostatic doses as HDR BT while respecting the OAR constraints. SBRT still remains an attractive treatment option for delivering hypofractionated treatments for prostate cancer compared to HDR BT, in particular as it is less invasive and less resource intensive. Long-term outcomes of clinical trials comparing HDR BT and SBRT "prostate boosts" may show whether the high intraprostatic doses are clinically significant and correlate with outcomes.

Distributed feedback lasers using surface gratings in Bragg waveguides.

This Letter presents, to the best of our knowledge, the first report of a narrow-linewidth ∼790-800nm edge-emitting semiconductor distributed feedback Bragg reflection waveguide diode laser (DFB2RL). The DFB2RLs were fabricated using a ridge waveguide structure with 5th order, surface-etched grating forming the wavelength selective element. Unbonded devices with a 500 µm cavity length exhibited continuous wave threshold currents in the region of 25 mA with an output power of 2.5 mW per (uncoated) facet at 100 mA drive current. The devices operated in a single longitudinal mode, with side-mode suppression ratio (SMSR) as high as 49 dB and linewidths as low as 207 kHz. Devices maintained single mode operation with high SMSR over a 9 nm wavelength range as the temperature was swept from 15°C to 50°C.

Acute Effects on the Human Peripheral Blood Transcriptome of Decompression Sickness Secondary to Scuba Diving.

Decompression sickness (DCS) develops due to inert gas bubble formation in bodily tissues and in the circulation, leading to a wide range of potentially serious clinical manifestations. Its pathophysiology remains incompletely understood. In this study, we aim to explore changes in the human leukocyte transcriptome in divers with DCS compared to closely matched unaffected controls after uneventful diving. Cases (n = 7) were divers developing the typical cutis marmorata rash after diving with a confirmed clinical diagnosis of DCS. Controls (n = 6) were healthy divers who surfaced from a ≥25 msw dive without decompression violation or evidence of DCS. Blood was sampled at two separate time points-within 8 h of dive completion and 40-44 h later. Transcriptome analysis by RNA-Sequencing followed by bioinformatic analysis was carried out to identify differentially expressed genes and relate their function to biological pathways. In DCS cases, we identified enrichment of transcripts involved in acute inflammation, activation of innate immunity and free radical scavenging pathways, with specific upregulation of transcripts related to neutrophil function and degranulation. DCS-induced transcriptomic events were reversed at the second time point following exposure to hyperbaric oxygen. The observed changes are consistent with findings from animal models of DCS and highlight a continuum between the responses elicited by uneventful diving and diving complicated by DCS. This study sheds light on the inflammatory pathophysiology of DCS and the associated immune response. Such data may potentially be valuable in the search for novel treatments targeting this disease.

Technical Note: Small field dose correction factors for radiochromic film in lung phantoms.

PURPOSE: Radiochromic film has been established as a detector that can be used without the need for perturbation correction factors for small field dosimetry in water. However, perturbation factors in low density media such as lung have yet to be published. This study calculated the factors required to account for the perturbation of radiochromic film when used for small field dosimetry in lung equivalent material. METHOD: Monte Carlo simulations were used to calculate dose to Gafchromic EBT3 film when placed inside a lung phantom. The beam simulated had a nominal energy of 6 MV and the field sizes simulated ranged from 10 × 10 mm2 to 30 × 30 mm2 . The lung density simulated was varied between 0.2 and 0.3 g/cm3 . Each simulation was repeated with the film replaced by lung material (the same as the surrounding medium), and the required correction factors for film dosimetry in lung ( D M e d , Q D D e t , Q ) were calculated by dividing the dose in lung by the dose in film. RESULTS: For field sizes 30 × 30 mm2 and larger, no correction factors were required. At a 20 × 20 mm2 field size, small corrections were required, but were within the approximate accuracy of film dosimetry (~2%). For a 10 × 10 mm2 field size, significant correction factors need to be applied (0.935 for lung density of 0.20 g/cm3 to 0.963 for lung density of 0.30 g/cm3 ). The values lower than one mean that the film is over-responding. At the "upstream" lung-water interface the correction factors were close to unity; while at the downstream interface the corrections required were marginally smaller to those at the center of lung. One centimeter or more away from the interfaces, the correction factor did not vary as a function distance from the interface (in the beam direction). Away from the central axis (perpendicular to the beam direction), the correction factors increased slightly (away from unity) as a function of off-axis distance, before abruptly changing direction at the penumbra, with the film actually under-responding by ~10% outside the field edges. CONCLUSION: Accurate dosimetry of very small fields (15 × 15 mm2 or smaller) using radiochromic film requires correction factors for the perturbation of the film on the surrounding lung material. This correction factor was as high as 6.5% for a 10 × 10 mm2 field size and a density of 0.2 g/cm3 . This will increase if either the density or the field size decrease further. This correction factor does not vary as a function of depth in lung once charged particle equilibrium is established.

Recommendations for simulating and measuring with biofabricated lung equivalent materials based on atomic composition analysis.

Monte Carlo simulations of lung equivalent materials often involve the density being artificially lowered rather than a true lung tissue (or equivalent plastic) and air composition being simulated. This study used atomic composition analysis to test the suitability of this method. Atomic composition analysis was also used to test the suitability of 3D printing PLA or ABS with air to simulate lung tissue. It was found that there was minimal atomic composition difference when using an artificially lowered density, with a 0.8 % difference in Nitrogen the largest observed. Therefore, excluding infill pattern effects, lowering the density of the lung tissue (or plastic) in simulations should be sufficiently accurate to simulate an inhaled lung, without the need to explicitly include the air component. The average electron density of 3D printed PLA and air, and ABS and air were just 0.3 % and 1.3 % different to inhaled lung, confirming their adequacy for MV photon dosimetry. However large average atomic number differences (5.6 % and 20.4 % respectively) mean that they are unlikely to be suitable for kV photon dosimetry.

Predicting the required thickness of custom shielding materials in kilovoltage radiotherapy beams.

The planning and delivery of kilovoltage (kV) radiotherapy treatments involves the use of custom shielding designed and fabricated for each patient. This study investigated methods by which the required thickness of custom shielding could be predicted for non-standard shielding materials fabricated using 3D printing techniques. Seven kV radiation beams from a WOmed T-300 X-ray therapy unit were modelled using SpekPy software, and AAPM TG-61 data were used to account for backscatter and spectral effects, for incrementally increasing thicknesses of Pb, W-PLA composite and Cu-PLA composite materials. The same beams were used to perform physical transmission measurements, and the thickness of each material required to achieve 5% beam transmission was determined. While the measured transmission factors for Pb, W-PLA and Cu-PLA shielding generally exceeded the calculated transmission factors, these differences had minimal effect on the derived thicknesses of shielding required to achieve 5% transmission, where calculations agreed with measurements within 0.5 mm for Pb at all available energies (70-300 kVp), within 1.4 mm for W-PLA at all available energies, and within 2.1 mm for Cu-PLA at superficial treatment energies (70-100 kVp). The incremental transmission factor calculation method described and validated in this study could be used, in combination with the conservative addition of 1-2 mm of additional material, to estimate shielding requirements for novel materials in therapeutic kilovoltage beams. However, if calculated shielding thicknesses equate to 10 mm or more, then additional verification measurements should be performed and the clinical suitability of the novel shielding material should be re-evaluated.

Assessing the suitability of a two-dimensional array for routine quality assurance checks of flatness and symmetry.

Quality assurance of radiotherapy linear accelerator beams demands the use of equipment with high resolution and reliability of reproducible results over time. This study examines the suitability of a commercially available two-dimensional ionization chamber array-the StarCheck array (PTW, Frieburg, Germany) to measure symmetry and flatness for both photon and electron beams. The study was conducted over a period of 4 years whereby the reliability of the array could be established. The reproducibility, uniformity of chamber response, and comparison of both photon and electron profiles acquired with the StarCheck array to that of the water-tank were examined. The most significant result was that across all profiles acquired using the StarCheck array, a defective chamber was detected, manifested by a 'dip' in the cross-plane profile at the same position. Assuming all detectors are functional, StarCheck was shown to be within 1% of the water-tank results for both flatness and symmetry. The detector array exhibited many calibration and detector issues over the period in which it has been used in the department. Furthermore, PTW recommends that recalibration of the array should to be performed every 2 years at either PTW, Freiburg, or at a qualified calibration laboratory. Therefore, the department requires a backup device for the recalibration time, approximately 4 months as worst case.

The effect of megavoltage field size on intrafraction cone-beam CT image quality.

To investigate the effects of scatter from a megavoltage treatment beam on intrafraction cone beam CT (CBCT) image quality. The effects of treatment beam field size and phantom geometry were investigated as well as the clinical success of IFI. Intrafraction imaging (IFI) was performed on four phantoms with four different MV field sizes using a 6 MV FFF source. The image quality of the intrafraction CBCT images was compared to that of a baseline CBCT (i.e. with no treatment beam on) and quantified using noise and low contrast visibility. Increasing the kV tube current was explored as a possible method to reduce noise induced by the MV photon scatter in the intrafraction-CBCTs. The clinical success of all IFI patients over a 2 month period was reviewed. Intrafraction-CBCT image quality and low-contrast visibility deteriorated as MV field size increased. The extent of image degradation was found to depend on the mass of the phantom resulting in a more pronounced effect for a pelvic phantom than a thoracic phantom. While increasing the tube current could reduce the noise in the intrafraction-CBCT images, increasing the current by a factor of 4 failed to reach baseline image quality. Anatomy was found to be the primary indication of clinical IFI failure with all observed failures occurring during abdominal treatments. Image quality was found to decrease with increasing MV field size and decrease with increasing treatment anatomy mass. When considering intrafraction imaging clinically, the primary indicator of IFI failure is treatment anatomy. IFI can be used during chest treatments with high success rates but care must be taken for abdominal treatments and failures should be expected.

Single-mode Bragg ring laser diodes.

We have designed and fabricated a monolithic semiconductor ring laser based on a Bragg waveguide structure. Through careful control of the waveguiding, we have overcome the inherent "leaky" nature of this waveguide mode and demonstrated a ring laser lasing in the Bragg mode. Best behavior was obtained from lasers with a diameter of 400 µm, where they exhibited output power ${ \gt }{1}\;{\rm mW}$>1mW, in continuous wave (CW) operation. A tangent waveguide provided access to the ring cavity using two ports through evanescent coupling. To meet the stringent waveguiding requirements imposed by the Bragg structure, a two-step etching process, consisting of a shallow-etched coupler and a deep-etched bend section of the ring, was developed in order to reduce the bend and scattering losses. The laser showed a threshold current density of ${\sim}{2.2}\;{{\rm kA/cm}^2}$∼2.2kA/cm2 in CW operation with single longitudinal mode operation with a signal-to-noise ratio of 30 dBm obtained at 1.5 ${I_{\rm th}}$Ith. Broadband phase-matching of $\chi ^{(2)}$χ(2) nonlinearity is observed, offering self-pumped parametric C-band conversion ${ \gt }{40}\;{\rm nm}$>40nm with efficiency of ${142}\% \;{{\rm W}^{ - 1}}\;{{\rm cm}^{ - 2}}$142%W-1cm-2.

Hyperbaric oxygen therapy awareness within a doctor population.

Hyperbaric medicine is a relatively young specialty that remains in the blind spot of most doctors' awareness. This study endeavors to identify the level of awareness of the indications for hyperbaric oxygen (HBO2) therapy among a doctor population in a developed country and factors which may improve referral rates. An anonymized questionnaire was distributed to doctors licensed to practice in Malta. Questions included physician specialty, demographics and previous exposure to diving and/or hyperbaric medicine. Moreover, two scoring systems were used to score subjects on HBO2-related topics. Binomial logistic regression models and generalized linear models were used in the statistical analysis. A total of 152 full replies were obtained and analyzed. Respondents who had visited a hyperbaric unit (HBU) (p=0.002) or attended a lecture on HBO2 (p=0.006) scored better than their counterparts, indicating better awareness of HBO2 indications and local chamber location. A previous HBU visit (p=0.001), being a hospital-based doctor (p=0.027) and a history of scuba diving (p=0.03) were associated with willingness to refer patients for HBO2 in the future. Encouraging visits to an HBU has been shown to be associated with multiple factors, which are expected to result in improved referral rates. Targeted educational sessions to doctors and medical students are likely to be beneficial in improving correct referral of patients for HBO2. The findings from this study may prove useful in improving appropriate referral rates of patients who may benefit from this useful treatment modality.

Whole Body Fat Free Mass and Vo2peak in Recreationally Active Men and Women.

BACKGROUND: Vo2peak has traditionally been thought to be regulated by cardiac output and arteriovenous-oxygen difference. A "muscle-centric" view suggests the cardiovascular system is secondarily responsive to the primary driver: active muscle mass.METHODS: A total of 19 recreationally active men (N = 10) and women (N = 9) performed a Vo2peak test, a Vo2peak verification test on an electrically braked cycle ergometer on the same day, and a hydrostatic weighing test to assess fat free mass after providing written informed consent.RESULTS: Vo2peak was significantly higher in men (3.74 ± 0.6 L · min-1) than women (2.22 ± 0.30 L · min-1). Whole body fat free mass explained 91% of the variability in Vo2peak (R² = 0.91) in the men and women combined, 81% of the variability in Vo2peak in men alone, and 46% of the variability in Vo2peak in women alone. None of these subjects were highly trained.DISCUSSION: Fat free mass, a surrogate for muscle mass, was the primary predictor of Vo2peak in this group of recreationally active men and women. Therefore, it appears that whole body fat free mass (a surrogate for muscle mass) is the primary driver for Vo2peak in these recreationally active men and women. These data have implications as to the type of training NASA personnel should be undertaking: resistance training as opposed to aerobic training.Lambert CP. Whole body fat free mass and Vo2peak in recreationally active men and women. Aerosp Med Hum Perform. 2020; 91(2):102-105.

Melanin Produced by the Fast-Growing Marine Bacterium Vibrio natriegens through Heterologous Biosynthesis: Characterization and Application.

Melanin is a pigment produced by organisms throughout all domains of life. Due to its unique physicochemical properties, biocompatibility, and biostability, there has been an increasing interest in the use of melanin for broad applications. In the vast majority of studies, melanin has been either chemically synthesized or isolated from animals, which has restricted its use to small-scale applications. Using bacteria as biocatalysts is a promising and economical alternative for the large-scale production of biomaterials. In this study, we engineered the marine bacterium Vibrio natriegens, one of the fastest-growing organisms, to synthesize melanin by expressing a heterologous tyrosinase gene and demonstrated that melanin production was much faster than in previously reported heterologous systems. The melanin of V. natriegens was characterized as a polymer derived from dihydroxyindole-2-carboxylic acid (DHICA) and, similarly to synthetic melanin, exhibited several characteristic and useful features. Electron microscopy analysis demonstrated that melanin produced from V. natriegens formed nanoparticles that were assembled as "melanin ghost" structures, and the photoprotective properties of these particles were validated by their protection of cells from UV irradiation. Using a novel electrochemical reverse engineering method, we observed that melanization conferred redox activity to V. natriegens Moreover, melanized bacteria were able to quickly adsorb the organic compound trinitrotoluene (TNT). Overall, the genetic tractability, rapid division time, and ease of culture provide a set of attractive properties that compare favorably to current E. coli production strains and warrant the further development of this chassis as a microbial factory for natural product biosynthesis.IMPORTANCE Melanins are macromolecules that are ubiquitous in nature and impart a large variety of biological functions, including structure, coloration, radiation resistance, free radical scavenging, and thermoregulation. Currently, in the majority of investigations, melanins are either chemically synthesized or extracted from animals, which presents significant challenges for large-scale production. Bacteria have been used as biocatalysts to synthesize a variety of biomaterials due to their fast growth and amenability to genetic engineering using synthetic biology tools. In this study, we engineered the extremely fast-growing bacterium V. natriegens to synthesize melanin nanoparticles by expressing a heterologous tyrosinase gene with inducible promoters. Characterization of the melanin produced from V. natriegens-produced tyrosinase revealed that it exhibited physical and chemical properties similar to those of natural and chemically synthesized melanins, including nanoparticle structure, protection against UV damage, and adsorption of toxic compounds. We anticipate that producing and controlling melanin structures at the nanoscale in this bacterial system with synthetic biology tools will enable the design and rapid production of novel biomaterials for multiple applications.

A photoactivatable crosslinking system reveals protein interactions in the Toxoplasma gondii inner membrane complex.

The Toxoplasma gondii inner membrane complex (IMC) is an important organelle involved in parasite motility and replication. The IMC resides beneath the parasite's plasma membrane and is composed of both membrane and cytoskeletal components. Although the protein composition of the IMC is becoming better understood, the protein-protein associations that enable proper functioning of the organelle remain largely unknown. Determining protein interactions in the IMC cytoskeletal network is particularly challenging, as disrupting the cytoskeleton requires conditions that disrupt protein complexes. To circumvent this problem, we demonstrate the application of a photoreactive unnatural amino acid (UAA) crosslinking system to capture protein interactions in the native intracellular environment. In addition to identifying binding partners, the UAA approach maps the binding interface of the bait protein used for crosslinking, providing structural information of the interacting proteins. We apply this technology to the essential IMC protein ILP1 and demonstrate that distinct regions of its C-terminal coiled-coil domain crosslink to the alveolins IMC3 and IMC6, as well as IMC27. We also show that the IMC3 C-terminal domain and the IMC6 N-terminal domain are necessary for binding to ILP1, further mapping interactions between ILP1 and the cytoskeleton. Together, this study develops a new approach to study protein-protein interactions in Toxoplasma and provides the first insight into the architecture of the cytoskeletal network of the apicomplexan IMC.

Increasing prevalence of vestibulo-cochlear decompression illness in Malta - an analysis of hyperbaric treatment data from 1987-2017.

INTRODUCTION: Scuba diving is a big part of the tourism sector in Malta, and all the cases of decompression illness (DCI)are treated within the single hyperbaric referral centre in the country. METHODS: This retrospective analysis reviews all the medical records of divers with DCI in Malta within the 30-year period between 1987 to 2017 who required recompression therapy with hyperbaric oxygen. RESULTS: There were 437 discrete cases of DCI managed with recompression therapy. Amongst DCI subtypes, the prevalence of musculo-skeletal DCI is decreasing, whereas that of vestibulo-cochlear DCI is increasing. CONCLUSION: The increasing prevalence of vestibulo-cochlear DCI may be due to a change in diving practices in Malta.