Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Title: Jealous protons sour another happy marriage; the story of how TRPV5 and PI(4,5)P(2) split up.

TRPV5 is a highly selective calcium channel that finetunes urinary calcium excretion by reabsorbing calcium from the pro-urine. New structural findings show how PTH and pH control TRPV5 activity by altering the binding of endogenous ligands calmodulin and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2))

TRP channels in calcium homeostasis: from hormonal control to structure-function relationship of TRPV5 and TRPV6.

Maintaining plasma calcium levels within a narrow range is of vital importance for many physiological functions. Therefore, calcium transport processes in the intestine, bone and kidney are tightly regulated to fine-tune the rate of absorption, storage and excretion. The TRPV5 and TRPV6 calcium channels are viewed as the gatekeepers of epithelial calcium transport. Several calciotropic hormones control the channels at the level of transcription, membrane expression, and function. Recent technological advances have provided the first near-atomic resolution structural models of several TRPV channels, allowing insight into their architecture. While this field is still in its infancy, it has increased our understanding of molecular channel regulation and holds great promise for future structure-function studies of these ion channels. This review will summarize the mechanisms that control the systemic calcium balance, as well as extrapolate structural views to the molecular functioning of TRPV5/6 channels in epithelial calcium transport

Broadband sub-THz spectroscopy modules integrated in 65-nm CMOS technology

The design and characterization of a broadband 20-480 GHz continuously tuneable on-chip spectrometer based on non-linear transmission lines in 65-nm CMOS technology is presented. The design procedure of the sampler that detects the ultra-broadband signal from the transmitter in time and frequency domain is described in detail. It consists of a non-linear transmission line, a passive pulse differentiator and a high-speed sample and hold-circuit. The relevance of the layout of the Schottky diodes in the sampler with a maximum RC-cutoff frequency of 430 GHz is described. Time domain and frequency domain measurements are presented to characterize the 480 GHz sampler bandwidth as well as the 3.1 ps sampler rise time. A signal to noise ratio of 90 dB at 100 GHz, 70 dB at 200 GHz and more than 30 dB at 480 GHz is reached. Two implementation of the spectrometer with antennas are presented, one with an on-chip antenna and one in a hybrid package. The antenna-less on-chip implementation of the transmitter and sampler requires no external lenses and is miniaturized to an area of 3 mm2. Future applications include analysis of fluids in microfluidic packages or droplet analysis in bio-medical or pharmaceutical applications

20GHz to 480GHz on-chip broadband spectrometer in 65-nm CMOS technology

The implementation and characterization of a 20 GHz to 480 GHz continuously tunable on-chip spectrometer in 65-nm CMOS technology is presented. The structure consists of a pulse generator based on a meandered nonlinear transmission line, a passive pulse differentiator and a high-speed sample and hold-circuit. Time domain and frequency domain measurements have been performed to characterize the spectrometer. A 3.1 ps fall time of the sampler is derived under optimized bias conditions. The spectrometer generates and detects a tunable frequency comb with frequency components between 20 GHz and 480 GHz, with a signal to noise ratio of 90 dB at 100 GHz, 70 dB at 200 GHz and 40 dB at 480 GHz. Due to the on-chip implementation of the transmitter and sampler, no external lenses are required and the circuit is integrated in an area of 3 mm2. It can be used for on-chip analysis of e.g. droplets in a microfluidic package

TRPV5 in renal tubular calcium handling and its potential relevance for nephrolithiasis

Contains fulltext : 215718pub.pdf (publisher's version ) (Closed access)Nephrolithiasis or renal stone disease is an increasingly common problem, and its relatively high recurrence rate demands better treatment options. The majority of patients with nephrolithiasis have stones that contain calcium (Ca(2+)), which develop upon "supersaturation" of the urine with insoluble Ca(2+) salts; hence processes that influence the delivery and renal handling of Ca(2+) may influence stone formation. Idiopathic hypercalciuria is indeed frequently observed in patients with kidney stones that contain Ca(2+). Genetic screens of nephrolithiasis determinants have identified an increasing number of gene candidates, most of which are involved in renal Ca(2+) handling. This review provides an outline of the current knowledge regarding genetics of nephrolithiasis and will mainly focus on the epithelial Ca(2+) channel transient receptor potential vanilloid 5 (TRPV5), an important player in Ca(2+) homeostasis. Being a member of the TRP family of ion channels, TRPV5 is currently part of a revolution in structural biology. Recent technological breakthroughs in the cryo-electron microscopy field, combined with improvements in biochemical sample preparation, have resulted in high-resolution 3-dimensional structural models of integral membrane proteins, including TRPV5. These models currently are being used to explore the proteins' structure-function relationship, elucidate the molecular mechanisms of channel regulation, and study the putative effects of disease variants. Combined with other multidisciplinary approaches, this approach may open an avenue toward better understanding of the pathophysiological mechanisms involved in hypercalciuria and stone formation, and ultimately it may facilitate prevention of stone recurrence through the development of effective drugs

High-resolution structures of transient receptor potential vanilloid channels: Unveiling a functionally diverse group of ion channels.

Contains fulltext : 220921.pdf (Publisher’s version ) (Open Access)Transient receptor potential vanilloid (TRPV) channels are part of the superfamily of TRP ion channels and play important roles in widespread physiological processes including both neuronal and non-neuronal pathways. Various diseases such as skeletal abnormalities, chronic pain, and cancer are associated with dysfunction of a TRPV channel. In order to obtain full understanding of disease pathogenesis and create opportunities for therapeutic intervention, it is essential to unravel how these channels function at a molecular level. In the past decade, incredible progress has been made in biochemical sample preparation of large membrane proteins and structural biology techniques, including cryo-electron microscopy. This has resulted in high resolution structures of all TRPV channels, which has provided novel insights into the molecular mechanisms of channel gating and regulation that will be summarized in this review.01 juli 202

Interspecies differences in PTH-mediated PKA phosphorylation of the epithelial calcium channel TRPV5.

Contains fulltext : 182321.pdf (Publisher’s version ) (Open Access)The epithelial calcium (Ca(2+)) channel TRPV5 (transient receptor potential vanilloid 5) is expressed in the distal convoluted tubule of the kidney and facilitates active Ca(2+) reabsorption. This process is instrumental for the maintenance of Ca(2+) homeostasis. Therefore, all aspects of TRPV5 function are tightly regulated by the calciotropic parathyroid hormone (PTH). Rabbit (rb)TRPV5 channel activity was shown to be stimulated upon PTH-mediated protein kinase A (PKA) phosphorylation. Since there is incomplete conservation of the PKA consensus motif (RR/QxT) across species, the aim of this study was to extend these findings to humans and characterize the expression and function of human (h)TRPV5. Functional differences between rbTRPV5 and hTRPV5 upon PTH stimulation were investigated using (45)Ca(2+) uptake assays, Fura-2 Ca(2+) imaging, and cell surface biotinylation. While PTH treatment enhanced rbTRPV5 channel activity, it did not stimulate hTRPV5 activity. Mutation of the human RQxT motif into rabbit RRxT (hTRPV5 Q706R) partially restored the sensitivity to PTH. An ancestral sequence reconstruction of TRPV5 orthologues demonstrated that the change in the RRxT motif coincides with the creation of another putative PKA motif (RGAS to RRAS) in the amino terminus of hTRPV5. Interestingly, a constitutively phosphorylated hTRPV5 mutant (hTRPV5 S141D) displayed significantly decreased channel function, while its plasma membrane abundance was increased. Taken together, PTH-mediated stimulation of TRPV5, via PKA, is not conserved in humans. Our data suggest that PTH regulation of TRPV5 is altered in humans, an important observation for future studies that may add to new concepts on the role of PTH in renal Ca(2+) handling

Structural insight into TRPV5 channel function and modulation

Contains fulltext : 203610.pdf (publisher's version ) (Closed access