Glutathione-dependent depalmitoylation of phospholemman by peroxiredoxin 6.

Phospholemman (PLM) regulates the cardiac sodium pump: PLM phosphorylation activates the pump whereas PLM palmitoylation inhibits its activity. Here, we show that the anti-oxidant protein peroxiredoxin 6 (Prdx6) interacts with and depalmitoylates PLM in a glutathione-dependent manner. Glutathione loading cells acutely reduce PLM palmitoylation; glutathione depletion significantly increases PLM palmitoylation. Prdx6 silencing abolishes these effects, suggesting that PLM can be depalmitoylated by reduced Prdx6. In vitro, only recombinant Prdx6, among several peroxiredoxin isoforms tested, removes palmitic acid from recombinant palmitoylated PLM. The broad-spectrum depalmitoylase inhibitor palmostatin B prevents Prdx6-dependent PLM depalmitoylation in cells and in vitro. Our data suggest that Prdx6 is a thioesterase that can depalmitoylate proteins by nucleophilic attack via its reactive thiol, linking PLM palmitoylation and hence sodium pump activity to cellular glutathione status. We show that protein depalmitoylation can occur via a catalytic cysteine in which substrate specificity is determined by a protein-protein interaction.

Microcantilever-integrated photonic circuits for broadband laser beam scanning.

Laser beam scanning is central to many applications, including displays, microscopy, three-dimensional mapping, and quantum information. Reducing the scanners to microchip form factors has spurred the development of very-large-scale photonic integrated circuits of optical phased arrays and focal plane switched arrays. An outstanding challenge remains to simultaneously achieve a compact footprint, broad wavelength operation, and low power consumption. Here, we introduce a laser beam scanner that meets these requirements. Using microcantilevers embedded with silicon nitride nanophotonic circuitry, we demonstrate broadband, one- and two-dimensional steering of light with wavelengths from 410 nm to 700 nm. The microcantilevers have ultracompact ~0.1 mm2 areas, consume ~31 to 46 mW of power, are simple to control, and emit a single light beam. The microcantilevers are monolithically integrated in an active photonic platform on 200-mm silicon wafers. The microcantilever-integrated photonic circuits miniaturize and simplify light projectors to enable versatile, power-efficient, and broadband laser scanner microchips.

The bidirectional relationship between endometriosis and microbiome.

Endometriosis has been described by many different theories of pathogenesis over the years. It is now also appreciated to be a state of chronic inflammation, and the role of immune dysfunction in its development has been proven. There is increasing evidence to support the role of the microbiome in the formation and progression of endometriosis via inflammatory pathways. The dysbiosis seen in endometriosis is thought to be both causative and a consequence of the pathogenesis. Gut, peritoneal fluid and female reproductive tract microbiota has been studied to understand if there are any microbiome signatures specific to endometriosis. New research on how to manipulate the microbiome for better detection and treatment of endometriosis is emerging.

External Validation of the "2021 AAGL Endometriosis Classification": A Retrospective Cohort Study.

STUDY OBJECTIVE: Externally validate the American Association of Gynecologic Laparoscopists (AAGL) staging system against surgical complexity and compare diagnostic accuracy with revised American Society for Reproductive Medicine (rASRM) stage, as was done in original publication. DESIGN: Retrospective, diagnostic accuracy study. SETTING: Multicenter (Sydney, Australia). PATIENTS: A total of 317 patients (January 2016-October 2021) were used in the final analysis. INTERVENTIONS: A database of patients with coded surgical data was analyzed. MEASUREMENTS AND MAIN RESULTS: Three independent observers assigned an AAGL surgical stage (1-4) as the index test and surgical complexity level (A-D) as the reference standard. Results from the most accurate of the 3 observers were used in the final analysis. The weighted kappa score for the overall performance of AAGL stage and rASRM to predict AAGL level was 0.48 and 0.48, respectively (no difference). This represents weaker agreement with AAGL level than was observed in the reference paper, which reported a weighted kappa of 0.62. Diagnostic accuracy (sensitivity, specificity, positive predictive value, and negative predictive value) for stage 1 to predict level A was 98.5%, 64.3%, 66.3%, and 98.3%; stage 2 to predict level B 31.2%, 90.5%, 27.0%, and 92.1 %; stage 3 to predict level C 12.3%, 94.1%, 59.3%, and 60.7%; stage 4 to predict level D 95.65%, 88.10%, 38.60%, and 99.62%. Area under the receiver operating characteristic curve for A vs B/C/D (cut point 9) was 0.87, A/B vs C/D (cut point 16) was 0.78, and A/B/C vs D (cut point 22) was 0.94. CONCLUSION: There was weak to moderate agreement between AAGL stage and AAGL surgical complexity level. Across all key indicators, the AAGL system did not perform as well in this external validation, nor did it outperform rASRM as it did in the reference paper. Results suggest the system is not generalizable.

Monolithically integrated, broadband, high-efficiency silicon nitride-on-silicon waveguide photodetectors in a visible-light integrated photonics platform.

Visible and near-infrared spectrum photonic integrated circuits are quickly becoming a key technology to address the scaling challenges in quantum information and biosensing. Thus far, integrated photonic platforms in this spectral range have lacked integrated photodetectors. Here, we report silicon nitride-on-silicon waveguide photodetectors that are monolithically integrated in a visible light photonic platform on silicon. Owing to a leaky-wave silicon nitride-on-silicon design, the devices achieved a high external quantum efficiency of >60% across a record wavelength span from λ ~ 400 nm to ~640 nm, an opto-electronic bandwidth up to 9 GHz, and an avalanche gain-bandwidth product up to 173 ± 30 GHz. As an example, a photodetector was integrated with a wavelength-tunable microring in a single chip for on-chip power monitoring.

Effectiveness of ultrasound for endometriosis diagnosis.

PURPOSE OF REVIEW: Endometriosis is a chronic benign gynaecological condition characterized by pelvic pain, subfertility and delay in diagnosis. There is an emerging philosophical shift from gold standard histopathological diagnosis through laparoscopy to establishing diagnosis through noninvasive imaging. RECENT FINDINGS: The ENZIAN classification system was updated in 2021 to be suitable for both diagnostic imaging and laparoscopy. The accuracy of transvaginal ultrasound (TVUS) in diagnosing endometriosis varies depending on location of the lesion. A recent international pilot study found that when ultrasound is performed in accordance with the IDEA consensus, a higher detection of deep endometriosis is seen, with an overall sensitivity of 88% and specificity of 79% compared with direct surgical visualization. SUMMARY: Although ultrasound can detect adenomyosis, deep endometriosis and endometriomas, it is not possible to reliably detect superficial endometriosis. In the instance of a negative ultrasound with persistence of symptoms despite medical therapy, laparoscopy should be considered for diagnosis and treatment.

'Seeing is believing': arguing for diagnostic laparoscopy as a diagnostic test for endometriosis.

Endometriosis is a benign disease that can cause pain and infertility in women. Debate exists over how endometriosis should best be diagnosed. On one hand, endometriosis can be diagnosed by directly examining pelvic anatomy via a surgical procedure known as diagnostic laparoscopy. On the other hand, the disease can be diagnosed via non-surgical means such as using medical imaging, the symptoms described by the patient and whether the patient responds to non-surgical therapies such as medication. In this debate article, we argue in favour of diagnostic laparoscopy. We review the safety of the procedure, compare the ability of diagnostic laparoscopy vs medical imaging to detect endometriosis and consider the benefits of formally diagnosing or ruling out the condition.

An Ultrasound-based Prediction Model to Predict Ureterolysis during Laparoscopic Endometriosis Surgery.

STUDY OBJECTIVE: To develop a model, including clinical features and ultrasound findings, to predict the need for ureterolysis (i.e., dissection of the ureter) during laparoscopy for endometriosis. DESIGN: A retrospective observational study of patients who had undergone transvaginal ultrasound (TVS) according to the International Deep Endometriosis Analysis consensus and subsequent laparoscopy ± excision of endometriosis between January 2017 and February 2021 was conducted. SETTING: Sydney Medical School Nepean, University of Sydney, Nepean Hospital, and Blue Mountains Hospital, New South Wales, Australia. PATIENTS/PARTICIPANT: 177 patients. INTERVENTION: The demographic, clinical, TVS, and intraoperative data were extracted through electronic clinical records. MEASUREMENTS AND MAIN RESULTS: Multicategorical decision-tree and baseline models were built to choose the variables most correlated to the outcome under study. Receiver operating characteristic analysis was performed on the binary classification. Based on our results, we selected the variables performing with significant statistical differences (p <.05). During the study period, 177 consecutive patients were recruited and divided into 2 subgroups, ureterolysis (51.4%) and nonureterolysis (48.6%). Ureterolysis was noted in 87.5% of patients in which the left ovary was immobile (p <.001) and in 82.5% in which the right ovary was fixed (p <.001). For patients with right uterosacral ligament (USL) deep endometriosis (DE), ureterolysis was performed in 96.2% patients (p <.001) and 64.6% (p = .043) for left USL DE. Among patients with bowel DE, the proportion of patients undergoing ureterolysis was 95.5% (p <.001). The prognostic variables used in the final model to predict ureterolysis included dyschezia, absence of ovarian mobility, presence of right or left USL DE, and presence of bowel DE on TVS. According to the developed model, the baseline risk for performing ureterolysis is 20% in our sample. The overall model performance demonstrated an area under the receiver operating characteristic curve 0.82. CONCLUSION: Our study demonstrates that it is possible to predict the need for ureterolysis with clinical and sonographic data. Furthermore, patients presenting with a combination of the variables of our model (dyschezia, ovarian immobility, USL, and bowel DE lesions) have a high risk of ureterolysis. In contrast, patients without these features have a low risk (approximately 20%) of needing ureterolysis.

Low-loss broadband bi-layer edge couplers for visible light.

Low-loss broadband fiber-to-chip coupling is currently challenging for visible-light photonic-integrated circuits (PICs) that need both high confinement waveguides for high-density integration and a minimum feature size above foundry lithographical limit. Here, we demonstrate bi-layer silicon nitride (SiN) edge couplers that have ≤ 4 dB/facet coupling loss with the Nufern S405-XP fiber over a broad optical wavelength range from 445 to 640 nm. The design uses a thin layer of SiN to expand the mode at the facet and adiabatically transfers the input light into a high-confinement single-mode waveguide (150-nm thick) for routing, while keeping the minimum nominal lithographic feature size at 150 nm. The achieved fiber-to-chip coupling loss is about 3 to 5 dB lower than that of single-layer designs with the same waveguide confinement and minimum feature size limitation.

Strength and Conditioning Practices and Perspectives of Volleyball Coaches and Players.

To the authors' knowledge this is the first study to describe the strength and conditioning (S&C) practices and perspectives of volleyball coaches and players. In total, 30 volleyball coaches (mean age 34.47 ± 7.83 years and coaching experience 19.57 ± 8.28 years), and 30 volleyball players (mean age 22.03 ± 4.43 years and playing experience 10.43 ± 8.98 years) completed an online survey with six sections: (a) informed consent; (b) background information; (c) education, qualifications, and prescription; (d) views on S&C; (e) exercise selection and preferences; and (f) issues and improvements. Frequency analysis was used to report responses to fixed-response questions and thematic-analysis for open-ended questions. While only one participant possessed an S&C certification, S&C was deemed 'important' to 'very important' for volleyball skills, physical fitness, and injury parameters. However, due to a reported lack of expertise, there appeared to be a theoretical understanding to practice gap. Furthermore, the implementation of S&C was considerably hindered by a lack of time, facilities, and equipment. National sports associations, coaches, and players can use the information within this study to provide an understanding of the current practices and perspectives of S&C in volleyball. While also promoting future developments in volleyball related S&C research and practice.

Back-side-on-BOX heterogeneously integrated III-V-on-silicon O-band discrete-mode lasers.

We demonstrate foundry-fabricated O-band III-V-on-silicon discrete-mode lasers. The laser fabrication follows the back-side-on-buried-oxide laser integration process and is compatible with complex, multilayer, silicon-on-insulator based platforms. A series of devices were characterized, with the best devices producing on-chip powers of nearly 20 mW with Lorentzian linewidths below 20 kHz and a side mode suppression ratio of at least 60 dB.

"Lessons from the extremes: Epigenetic and genetic regulation in point monocentromere and holocentromere establishment on artificial chromosomes".

The formation of de novo centromeres on artificial chromosomes in humans (HACs) and fission yeast (SpYACs) has provided much insights to the epigenetic and genetic control on regional centromere establishment and maintenance. Similarly, the use of artificial chromosomes in point centromeric budding yeast Saccharomyces cerevisiae (ScYACs) and holocentric Caenorhabditis elegans (WACs) has revealed epigenetic regulation in the originally thought purely genetically-determined point centromeres and some centromeric DNA sequence features in holocentromeres, respectively. These relatively extreme and less characterized centromere organizations, on the endogenous chromosomes and artificial chromosomes, will be discussed and compared to the more well-studied regional centromere systems. This review will highlight some of the common epigenetic and genetic features in different centromere architectures, including the presence of the centromeric histone H3 variant, CENP-A or CenH3, centromeric and pericentric transcription, AT-richness and repetitiveness of centromeric DNA sequences.

Performance measures in inflammatory bowel disease surveillance colonoscopy: Implementing changes to practice improves performance.

BACKGROUND AND AIM: Dye-based chromoendoscopy (DCE) with targeted biopsies is recommended for inflammatory bowel disease (IBD) surveillance. However, DCE has not yet been widely adopted into clinical practice. We evaluated quality indicators in IBD surveillance following introduction of structured changes in service delivery. METHODS: In August 2016, we introduced a number of changes to IBD surveillance practice in our endoscopy unit. These included training using interactive videos/images in a structured module, DCE as standard by using a foot-pedal operated pump jet, allocation of 45-minute procedure timeslots, targeted biopsies (except in high-risk patients), scoring of endoscopic disease activity, and lesion detection/morphology characterization. All IBD surveillance colonoscopies were allocated to a small team of four DCE-trained endoscopists. We compared quality measures for surveillance procedures carried out pre- and post-August 2016. The two groups were compared using chi-squared statistics RESULTS: A total of 598 IBD surveillance procedures (277 pre-August 2016 and 321 post-August 2016) were done and included in the study. Use of DCE increased (54.2% vs 76.0% P < 0.0005) whereas random biopsy surveillance decreased (12.3% vs 3.1% P < 0.0005). Use of Paris classification (26.1% vs 57.0% P < 0.0005) and Kudo pit pattern increased (21.7% vs 59.0% P < 0.0005). There was also an increase in lesion detection rate (24.9% vs 33.1% P < 0.05). CONCLUSIONS: Implementation of extensive changes in practice of surveillance colonoscopy resulted in significant improvement in quality indicators within a short period of time. Training, education and audit may continue to facilitate the adoption of DCE and further improve quality of performance in IBD surveillance.

Visible-light silicon nitride waveguide devices and implantable neurophotonic probes on thinned 200 mm silicon wafers.

We present passive, visible light silicon nitride waveguides fabricated on ≈ 100 µm thick 200 mm silicon wafers using deep ultraviolet lithography. The best-case propagation losses of single-mode waveguides were ≤ 2.8 dB/cm and ≤ 1.9 dB/cm over continuous wavelength ranges of 466-550 nm and 552-648 nm, respectively. In-plane waveguide crossings and multimode interference power splitters are also demonstrated. Using this platform, we realize a proof-of-concept implantable neurophotonic probe for optogenetic stimulation of rodent brains. The probe has grating coupler emitters defined on a 4 mm long, 92 µm thick shank and operates over a wide wavelength range of 430-645 nm covering the excitation spectra of multiple opsins and fluorophores used for brain stimulation and imaging.

Multi-layer silicon nitride-on-silicon polarization-independent grating couplers.

A polarization-independent grating coupler is proposed and demonstrated in a 3-layer silicon nitride-on-silicon photonic platform. Polarization independent coupling was made possible by the supermodes and added degrees of geometric freedom unique to the 3-layer photonic platform. The grating was designed via optimization algorithms, and the simulated peak coupling efficiency was -2.1 dB with a 1 dB polarization dependent loss (PDL) bandwidth of 69 nm. The fabricated grating couplers had a peak coupling efficiency of -4.8 dB with 1 dB PDL bandwidth of over 100 nm.

Silicon nitride-on-silicon bi-layer grating couplers designed by a global optimization method.

Silicon nitride-on-silicon bi-layer grating couplers were designed for the O-band using an optimization-based procedure that accounted for design rules and fabricated on a 200 mm wafer. The designs were sufficiently robust to fabrication variations to function well across the wafer. A peak fiber-to-chip coupling efficiency to standard single mode fiber of -2.2 dB and a 1-dB bandwidth of 72.9 nm was achieved in the representative device. Over several chips across the wafer, we measured a median peak coupling efficiency of -2.1 dB and median 1-dB bandwidth of 70.8 nm. The measurements had good correspondence with simulation.

Flip-chip integrated silicon Mach-Zehnder modulator with a 28nm fully depleted silicon-on-insulator CMOS driver.

We present a silicon electro-optic transmitter consisting of a 28nm ultra-thin body and buried oxide fully depleted silicon-on-insulator (UTBB FD-SOI) CMOS driver flip-chip integrated onto a Mach-Zehnder modulator. The Mach-Zehnder silicon optical modulator was optimized to have a 3dB bandwidth of around 25 GHz at -1V bias and a 50 Ω impedance. The UTBB FD-SOI CMOS driver provided a large output voltage swing around 5 Vpp to enable a high dynamic extinction ratio and a low device insertion loss. At 44 Gbps, the transmitter achieved a high extinction ratio of 6.4 dB at the modulator quadrature operation point. This result shows open eye diagrams at the highest bit rates and with the largest extinction ratios for silicon electro-optic transmitter using a CMOS driver.

Binary particle swarm optimized 2 × 2 power splitters in a standard foundry silicon photonic platform.

Compact power splitters designed ab initio using binary particle swarm optimization in a 2D mesh for a standard foundry silicon photonic platform are studied. Designs with a 4.8 µm×4.8 µm footprint composed of 200 nm×200 nm and 100 nm×100 nm cells are demonstrated. Despite not respecting design rules, the design with the smaller cells had lower insertion losses and broader bandwidth and showed consistent behavior across the wafer. Deviations between design and experiments point to the need for further investigations of the minimum feature dimensions.