Carpal tunnel is an important anatomical passage that carries the flexor tendons into the hand. As there is still no consensus about its contents among the anatomy textbooks, the main purpose of this study was to identify the relations of the flexor carpi radialis tendon in the carpal tunnel.This retrospective study was completed in April 2018 at authors’ university’s hospital. Seventy-four female and 44 male patients’ wrists without any pathology were examined by using magnetic resonance images. The series of axial sections where the pisiform exist were evaluated by using T1 sequence and the structures in the carpal tunnel were identified.Results of this study showed that the tendon of the flexor carpi radialis was found above the flexor retinaculum within its own septal compartment in all patients.According to the results, tendon of flexor carpi radialis crosses the wrist region superficial to the carpal tunnel. Thus, tendon of flexor carpi radialis doesn’t have any effect on the carpal tunnel syndrome. Further cadaveric studies would be useful for identifying the contents of the carpal tunnel and morphological organization of the wrist. The antebrachial fascia, anteriorly, is continuous superficially as palmar carpal ligament and distally and deeply as a strong fibrous band; the flexor retinaculum  . At the medial aspect of the wrist, ulnar artery and nerve pass through a tunnel between these ligaments, which is termed as the ulnar tunnel  [3]. The roof and floor of the canal is bordered by palmar carpal ligament and transvers carpal ligament, respectively [1–3]. Thick flexor retinaculum also encloses the carpal groove superiorly and forms a passageway on the palmar side of the wrist . The carpal tunnel is an osseo-fibrous tunnel which is bordered superiorly by transverse carpal ligament and the base consist of the hook of hamate, triquetrum, and pisiform bones medially; scaphoid and the trapezium bones laterally . The tendons of the flexor muscles of the fingers and the median nerve pass through the tunnel . Most of the textbooks mentioned that 10 structures traverse the tunnel including the 9 tendons which are flexor digitorum superficialis and profundus, and palmaris longus and the median nerve . On the anterior surface of the wrist, the flexor retinaculum and palmar carpal ligament held the tendons of the flexor muscles in the tunnel [9]. The tendon of the flexor carpi radialis (FCRt) passes through a vertical groove on the trapezium within its own tunnel at the wrist region, which is separated from the carpal tunnel by the deep portion of the transverse carpal ligament and inserts on the palmar surface of the base of the second and third metacarpal . In addition to this well-known information, it is also mentioned that FCRt found within the carpal tunnel in its own tunnel [8]. Previous studies have focused on describing the carpal tunnel’s borders and related structures by using different methods to identify the safe zones for carpal tunnel release [12–14]. MRI and ultrasound methods are used for identification of the course of FCRt and diagnosing the wrist pathologies [15–18]. Carpal tunnel syndrome is the most common entrapment neuropathy characterized by tingling, burning, pain, and paresthesia in the first 3 radial digits and radial half of the forth digit due to the compression of the median nerve in the carpal tunnel [19–22]. Although it has been widely studied, while mentioning the contents of the carpal tunnel, differences could be seen among the textbooks . There is no conflict about the fact that the tendons of flexor digitorum superficialis, flexor digitorum profundus, flexor pollicis longus, and the median nerve are located inside the carpal tunnel. The presence of the tendon of flexor carpi radialis in the tunnel could be confusing. The aim of this study is to reveal the relationship between FCRt and carpal tunnel. Thus, the borders and contents of the carpal tunnel could be described easily. Results of this study could make an important contribution to the literature and support the diagnostic studies about carpal tunnel syndrome.This study was carried out in pursuit of receiving the ethical approval from the local ethics committee (GO 17/887-15) and completed according to the principles of the Helsinki Declaration.Retrospectively, 118  wrist regions MRI scans were evaluated. None of the patients had surgery or trauma history. Patients with wrist pathology were excluded. The mean age of the patients was 35.7 (range: 9–74). In addition, 3 fresh-frozen upper limb cadavers were dissected to demonstrate the course of the flexor carpi radialis tendon.Wrist MRI evaluations were completed using any of three 1.5 Tesla scanners in the radiology department . MRI protocols were performed while patients were in the supine position. The radiology department’s routine MRI protocol consisted of coronal, sagittal, and transverse T2-weighted spin-echo and sagittal and transverse T1-weighted spin-echo with 3.0–3.5 mm slice thickness. All patients’ MRI series were obtained from the Picture Archiving and Communication System (PACS) at authors’ university hospital. All evaluations were completed by a 20 year experienced anatomy professor, a 15-year experienced anatomy specialist, a 6-year experienced anatomy specialist and a 20-year experienced orthopedic associated professor by using Osirix-Lite version 9 .To standardize the evaluation, the series of axial sections from the level of pisiform bone were examined. First location of the FCRt, proximally to the carpal tunnel was detected. Afterward the course of the tendon was followed till it passed through the carpal tunnel and its location according to the flexor retinaculum was observed. While dissecting the fresh-frozen cadavers, first incision was applied vertically from the anterior surface of the middle of the forearm to the proximal part of the palmar surface of the hand. The skin and superficial connective tissues were deviated carefully to view the muscle groups of the anterior compartment of forearm and the flexor retinaculum. The entire course of tendons of the flexor muscles were evaluated.In all MRI series the flexor tendons of the digits and median nerve were located below the flexor retinaculum while the FCRt was located above the flexor retinaculum within its own septal compartment . Likewise, the cadaveric dissections also executed that the flexor tendons of digits and median nerve were covered by flexor retinaculum within the carpal tunnel and, a completely different and separated compartment of the FCRt was found above the flexor retinaculum . At wrist region distal continuation of the antebrachial fascia forms superficially the palmar carpal ligament and deeply the flexor retinaculum  . Between palmar carpal ligament and flexor retinaculum guyon canal is found which includes ulnar artery and nerve [3]. Strong fibrous flexor retinaculum forms the roof of the carpal tunnel . It is important to define the flexor retinaculum’s boundaries precisely to identify the contents of carpal tunnel. Furthermore, this will lead to creating common terminology between the anatomy and clinical sciences. The FCR muscle is found at the anterior compartment of the forearm and mainly flexes and to a lesser extend radially rotates the wrist [16]. Although its morphological and clinical importance has been widely studied, there is still no consensus about its relationship with the carpal tunnel . Most of the textbooks mentioned that 10 structures traverse the tunnel including the 9 tendons including flexor digitorum superficialis and profundus, and palmaris longus and the median nerve . However, some other textbooks mention that the FCRt found in the tunnel [8]. Morphological studies have demonstrated that the FCRt was not included in the contents of the carpal tunnel . Chamas et al. described as FCRt forms the lateral border of the carpal tunnel in a morphological study that focused on the explaining the boundaries of carpal tunnel [7]. The FCRt is covered by a fibro-osseous tunnel which is adjacent to the flexor retinaculum of the carpal tunnel . This tunnel is formed proximally by the scaphoid, the flexor retinaculum, and a vertical retinacular septum and, distally, by trapezium, again the flexor retinaculum, and the vertical retinacular septum [10]. This vertical retinacular septum separates the FCRt from the carpal tunnel . Also, it is usually used as donor in tendon transfers and reconstructive surgeries of the forearm . Due to this proximity, any disorder like tenosynovitis of the FCRt may imitate carpal tunnel syndrome [10]. Therefore, FCR tenosynovitis should be considered in the differential diagnosis of carpal tunnel syndrome and a detailed examination should be performed.According to the results of this study, the FCRt crosses the wrist superficial to the carpal tunnel. Thus, the FCRt may not be included as a factor in the etiology of the carpal tunnel syndrome but the close relationship must be in mind that the pathologies may imitate the carpal tunnel syndrome. Further multidisciplinary studies would be useful for identifying the contents of the carpal tunnel, the morphological organization of the wrist, and the biomechanical etiologies and mechanisms of the carpal tunnel syndrome.Although, the well-known theoretical information about the carpal tunnel, there is still no consensus about situation of the FCRt in major anatomy textbooks. Therefore, this study was demonstrated the precise situation of the tendon of the flexor carpi radialis with the carpal tunnel. Results verified that the FCRt does not pass through the carpal tunnel, but it passes through its own compartment that is formed by the flexor retinaculum. The main limitation of the present study was the lack of cadaveric measurements due to the insufficient number of specimens. Moreover, a histological investigation should be performed to understand the course of the flexor retinaculum. This study was carried out in pursuit of receiving the ethical approval from the local ethics committee (GO 17/887-15) and completed according to the principles of the Helsinki Declaration.


However, different surgical table orientations can impact access to different work zones, areas and equipment in the OR, potentially impacting workflow of surgical team members and creating patient safety risks; (2) Methods: This quantitative observational study used a convenience sample of 38 video recordings of the intraoperative phase of pediatric outpatient surgeries to study the impacts of surgical table orientation on flow disruptions (FDs), number of contacts between team members and distance traveled; (3) Results: This study found that the orientation of the surgical table significantly influenced staff workflow and movement in the OR with an angled surgical table orientation being least disruptive to surgical work. The anesthesia provider, scrub nurse and circulating nurse experienced more FDs compared to the surgeon; (4) Conclusions: The orientation of the surgical table matters, and clinicians and architects must consider different design and operational strategies to support optimal table orientation in the OR. Optimal patient positioning is a critical part of any surgical procedure and the wrong position of the patient in the operating room (OR) during surgery can cause patient harm and injury with effects ranging from minor aches, pains and skin abrasions to paralysis and loss of life ,2,3. TheOperating rooms for general surgeries are usually designed around a standard position of the surgical table centered and parallel to the walls of the room with the assumption that most surgeries would be conducted in this orientation, with table rotation required for a smaller set of surgery types. In this standard position, the anesthesiologist is usually located at the head of the patient with the surgeon and scrub nurse located on either side of the patient depending on the surgical site location. The organization of fixed and difficult-to-move equipment and storage are usually optimized for this position of the surgical table. However, the surgical table is often rotated to accommodate different surgery types or surgeon preferences, requiring modifications to the position of the anesthesia workspace and moveable equipment associated with anesthesia and surgical activities as well as the surgical team members during surgery. These different orientations of the surgical table may pose workflow challenges and patient safety risks to the patient.In a highly interconnected and complex system like the operating room, a significant change or disruption to one part of the system potentially impacts other parts as well. For example, a particular orientation of the surgical table might result in more workspace or easier access to the surgical site for the surgeon while resulting in crowding for the scrub nurse or increasing the distance between anesthesia monitoring devices and the patient, creating challenges for the anesthesia team and safety risks for the patient. The operating room environment is a highly complex system, and efficient and safe delivery of patient care depends on understanding and supporting the dynamic and changing relationships between the surgical team members, patient, tasks, equipment and the physical environment of the OR. Several studies show that disruptions are frequent during surgical procedures and poor room and equipment ergonomics are major contributing factors . SpecifiA recent study showed that the rate of major FDs in the OR increased as the rate of minor FDs increased, and this was particularly true for disruptions that involved OR equipment . This stCertain orientations of the surgical table may result in some areas and access to certain equipment or workspaces in the OR being obstructed during the intraoperative phase, requiring team members to take alternative and undesirable paths to get to equipment or storage. This may lead to unnecessary travel within the OR and unwanted contacts between team members. For example, non-sterile team members (circulating nurse or anesthesia provider) may need to pass near sterile team members (surgeon and scrub nurse) to get to storage and equipment. Taaffe et al.  found thHow do different types of surgical table orientations impact the workflow of surgical team members?How do different types of surgical table orientations impact the overall movement of surgical team members during the intraoperative phase of the surgery?This study utilizes the Systems Engineering Initiative for Patient Safety 2.0 (SEIPS 2.0) framework  to studyThis observational study used a convenience sample of 38 video recordings of pediatric outpatient surgeries from four different ORs at the Medical University of South Carolina (MUSC). This study complied with the American Psychological Association Code of Ethics and was approved by the Institutional Review Board at MUSC where observations were conducted (study ID: Pro00048787).The video recordings of surgeries were captured using four video cameras located in four corners of the operating room such that all parts of the OR were visible. The video recordings were initiated when the patient entered the room and ended when the patient exited the room. The videos were then coded for surgery phases, surgical table orientation, team member locations, and flow disruptions using Noldus Observer XT V.12. Two researchers with human factors training coded the videos. All coders observed a set of 8 pre-recorded surgeries from a different OR and familiarized themselves with the coding scheme prior to coding. Coders also participated in two training sessions where they received education from human factors and clinical experts on human factors issues in the OR and also the overall goals and protocol related to the current study. The coding was conducted in parallel over three rounds until there was consensus. Percentage agreement over 83% was obtained for flow disruption and location codes using an index of concordance.Each video recording was first coded to mark different surgery phases  such that the duration of each phase could be obtained and the analysis could focus on activities within that phase. This study focuses on the intraoperative phase which was defined as the duration between the incision to the surgical site of the patient and the closure of the surgical site. The plan of the operating room was drawn to demarcate different functional zones, which were bounded and defined according to the type of function conducted in them . The locFour different table orientations were identified: (A) the surgical table angled in the room with the head of the table in the anesthesia zone (orientation A), (B) parallel to the long or short walls (depending on shape of room) of the room with the head of the surgical table in the anesthesia zone (orientation B), (C) parallel to the long or short walls of the room (depending on room shape) with the anesthesia zone perpendicular to the head of the patient (orientation C) or (D) angled in the room with the anesthesia zone adjacent to the head of the surgical table (orientation D) . The zonIn this study, the impact of the different surgical table orientations on staff workflow was understood by studying FDs. Flow disruptions were coded for all surgical team members  using an existing taxonomy developed by Palmer and colleagues  and adapThis study also focused on understanding how different surgical table orientations impact the movement of surgical team members during the intraoperative phase. The data obtained from video coding of the surgeries were used to create a playback simulation using AnyLogic simulation software. Data on staff movement and interaction during the intraoperative phase was obtained from the software platform which was customized to track the location of all team members with the required degree of precision and to obtain measures related to the overall movement of all team members such as the total distance traveled (m) and the total number of contacts per surgery. A contact was calculated by monitoring the distance between any two subjects in the operating room in the playback model. When another subject passed or was within a prespecified threshold of (0.6 m) of another, a contact was recorded.The event-based data around FDs obtained from the Noldus Observer XT 12 software  were converted into time-based data with 1 s intervals to facilitate statistical analysis. Data on distance traveled and number of contacts was obtained from the AnyLogic simulation software program. Descriptive statistics were used to report characteristics of FDs and movement patterns (distance traveled and number of contacts) associated with different types of surgical table orientations across the intraoperative phases of the observed pediatric surgeries.The analysis was conducted at the surgical team member level with data counting the number of FDs, the distance traveled, and the number of contacts for each person in the operating room during the intraoperative phase. Each person in the room was coded according to their role in the surgical team  and there could be more than one provider for each type during the surgical case.Quasi-Poisson regression models were used to examine the impact that surgical table orientation had on the number of FDs. Quasi-Poisson regression is a generalization of the Poisson regression model and estimates the over-dispersion and does not assume that the mean and variance are equal. These models were used to predict the count of all FDs, the count of major FDs, and the count of minor FDs during the intraoperative phase of the surgery.In addition to the overall FD analysis, binary indicator variables were created to identify if during the intraoperative phase each person in the OR experienced any flow disruption of a specific type. Specifically, the indicator variables were created to identify if a healthcare worker was involved in a layout FD, an environmental hazard FD, an interruption FD, an equipment FD, or a usability FD. Binary logistic regression models were used to evaluate the likelihood of an individual being involved in any of the specific FD types. Explanatory variables considered in the analysis included binary indicator variables for the surgical table orientation, the provider types, and the specific operating room where the surgery was conducted. The position of the surgical site was also accounted for since this might impact the position of the surgical team around the patient. The surgeries were categorized as upper body  and lower body . Additionally, the number of people in the operating room and the duration of the intraoperative phase were included as explanatory variables. All statistical analysis was conducted in R Studio version 1.4.1103 . Stepwise deletion was used to remove insignificant parameters from the models.Thirty-eight pediatric surgeries conducted in four different ORs were video recorded and analyzed. The quasi-Poisson regression model predicting all flow disruptions during the intraoperative surgical phase is shown in The quasi-Poisson regression model predicting minor flow disruptions during the intraoperative surgical phase is shown in The quasi-Poisson regression model predicting major FDs during the intraoperative surgical phase is shown in The results of several binary logistic regression models suggest that individuals working in ORs with table orientation A were less likely to experience a layout FD , controlling for the duration of the surgery. Individuals working in surgeries with table orientation D were less likely to experience a usability FD  with circulating nurses also less likely to experience a usability FD . There were no significant table orientations that predicted the likelihood of individuals experiencing an equipment, environmental hazard, or an interruption FD during the intraoperative phase of the surgery.The total distance traveled by surgical team members during the intraoperative phase across all observed surgeries was 6776 m. Team members traveled an average of 178.3 m/surgery and 8.13 ± 3.9 m/min during the intraoperative phase of a surgery . The cirA logistic regression model predicting the likelihood that an individual was in the 4th quartile of estimated distance moved during the intraoperative surgical phase is shown in The total number of contacts recorded between team members during the intraoperative phase when they passed each other within a prespecified threshold (0.6 m) was 1789. The Quasi-Poisson regression model predicting the number of contacts for each individual in the OR during the intraoperative phase is shown in This is the first quantitative observational study to examine how the work of the surgical team is impacted by different types of surgical table orientations. This study found that the orientation of the surgical table within the operating room significantly influenced staff workflow and movement in the OR during the intraoperative phase of surgery. More specifically, FDs during the intraoperative phase were 1.48 times higher when the surgical case used orientation B  and 1.79 times higher with orientation D  after controlling for other variables. The findings were similar for minor FDs, though there was no impact of surgical table orientation on the number of major FDs. This study also demonstrated that surgical team members were less likely to experience a layout related FD in surgeries conducted in the angled surgical table orientation A  compared to all other orientations. Team members working in operating rooms with surgical table orientation C  with the anesthesia zone perpendicular to the head of the patient) were 2.82 times more likely to experience contacts with other team members. The average number of contacts/min was least for all team members in orientation A. The study also found that individuals working in orientation B were more likely to walk longer distances during the intraoperative phase.A key insight from this study is that surgical table orientation matters with the angled orientation A impacting fewer flow disruptions, specifically the occurrence of layout related disruptions. A previous simulation-based study found that the angled surgical table orientation was preferred as it provided space for movement in the room without increasing the number of contacts . This obOn the other hand, orientation B and D resulted in a higher number of FDs during the intraoperative phase. While table orientation B is close in configuration to the angled orientation A, there were significantly more FDs in this orientation. In ORs with narrow space available at the foot of the table , the circulation space at the foot of the table may get blocked with equipment during the intraoperative phase requiring team members to find alternative (and often undesirable) paths to get to the storage and equipment. This may result in unwanted contacts, more disruptions and greater travel within the OR. The angling of the surgical table opens up space at the foot of the table, potentially helping to reduce some of these challenges. The higher number of FDs in orientation D can be explained by the spatial constraints of accommodating the surgeon and anesthesia provider and other stored equipment in a limited workspace in the corner of the room.This study also found that surgical team members are impacted differently by different orientations of the surgical table. The surgeon and scrub nurse experienced fewer FD/min in orientation A compared to orientation D. Overall, the anesthesia provider, circulating nurse and scrub nurses experienced more FDs during the intraoperative phase compared to the surgeon. An interesting finding from this study is that the scrub nurse experienced 1.78 times more major FDs compared to other team members. This may suggest that while the position of the table is optimized for the surgeon, the scrub nurse who is assisting the surgeon from the opposite side of the table, may be constrained for space and may experience major disruptions to their work. This study also found that circulating nurses and scrub nurses walked much more than other providers in the OR. The movement of the circulating nurse in the OR is expected, given the requirements of their role to monitor and support the team during surgery. However, the scrub nurse is usually fairly stationary during the intraoperative phase and the movements of this individual (while less than that of the circulating nurse) may be indicative of layout challenges requiring frequent adjustments to accommodate equipment or other staff in the OR. This study also confirms findings from other OR studies that showed the negative impacts of increased number of people in the OR ,22. In tThe findings from this study have significant implications for both OR design and clinical practice. This study suggests that OR designers and administrators should not only reconsider standard surgical table positions and associated locations of different functional zones in the design and layout of ORs, but should also evaluate layout and workflow in the context of different surgical table orientations. Simulation-based evaluations that allow teams to enact surgical procedures in different surgical table orientations in a physical mock-up may help in proactively identifying and mitigating workflow challenges . In thisFrom a clinical standpoint, this study highlights the workflow challenges experienced by surgical team members in different orientations. Some of these surgical table orientations may be required for certain types of surgeries. However, to the extent possible, surgeries should be conducted in standard surgical table orientations which support workflows for all team members. OR managers, administrators and clinicians should also be cognizant of spatial constraints posed in certain orientations such as C and D and prevent accumulation of equipment and clutter in the OR that may further exacerbate workflow challenges in these orientations. While this study did not measure incidence of patient harm or injury associated with different surgical table orientations, other studies have shown that high rates of FDs contribute to surgical errors ,15 and iThis study is arguably the most detailed analysis of the relationship between surgical table orientation and surgical workflow in the OR ever conducted. By using a systems approach, we were able to study the dynamic interactions between surgical team members and their work in the context of different spatial layout conditions (table orientation). The type of data obtained from the 38 general pediatric surgeries is very extensive. However, this study has some limitations. While this study included data from all individual team members across these surgeries, it is a relatively small sample. Further, different types of pediatric surgeries were included in this sample. While the surgeries were categorized based on surgical site location given its relevance for positioning of team members, it is possible that specific variations among procedures could potentially confound findings. Given that this is the first extensive study of its kind on surgical table positioning and orientation in surgery and that table rotations are common in all types of ORs, there is a critical need to expand this work to other types of surgical environments.The layout of the operating room, especially the position of the surgical table, significantly impacts the work of all surgical team members by impacting flow disruptions as well as movement in the operating room. Utilizing a systems approach, this study found that an angled surgical table orientation is optimal for supporting the work of all team members in general pediatric surgeries while other orientations may cause challenges to workflow and movement. There are key areas of improvement identified in this study that are relevant for architects as well as clinicians and administrators.


Although the exact pathogenetic mechanisms leading to age-related macular degeneration (AMD) have not been clearly identified, oxidative damage in the retina and choroid due to an imbalance between local oxidants/anti-oxidant systems leading to chronic inflammation could represent the trigger event. Different in vitro and in vivo models have demonstrated the involvement of reactive oxygen species generated in a highly oxidative environment in the development of drusen and retinal pigment epithelium (RPE) changes in the initial pathologic processes of AMD; moreover, recent evidence has highlighted the possible association of oxidative stress and neovascular AMD. Nitric oxide (NO), which is known to play a key role in retinal physiological processes and in the regulation of choroidal blood flow, under pathologic conditions could lead to RPE/photoreceptor degeneration due to the generation of peroxynitrite, a potentially cytotoxic tyrosine-nitrating molecule. Furthermore, the altered expression of the different isoforms of NO synthases could be involved in choroidal microvascular changes leading to neovascularization. The purpose of this review was to investigate the different pathways activated by oxidative/nitrosative stress in the pathogenesis of AMD, focusing on the mechanisms leading to neovascularization and on the possible protective role of anti-vascular endothelial growth factor agents in this context. Age-related macular degeneration (AMD) is a complex multifactorial retinal degenerative disease primarily affecting the macula and progressively leading to irreversible central vision loss. It is the first cause of blindness in the Western world, with an estimation of up to 18.6 million people being affected by the blinding stages of the disease by 2040 worldwide . The ConThe exact pathogenetic mechanisms leading to AMD are still not fully understood; however, it is well known that AMD is a multifactorial disease with multiple genetic and environmental factors contributing to its onset and progression ,9,10,11.The present review will concentrate on the role of oxidative and nitrosative stress in the initiation and progression of AMD, with particular attention on the mechanisms leading to the formation of neovascularization in the context of AMD and the possible protective role of anti-vascular endothelial growth factor (VEGF) agents in this context.The maintenance of a physiologic relationship between the different components of the CC/BrM/RPE/photoreceptor complex is of primary importance to preserve its correct functioning and the breakdown of this equilibrium is involved in the changes occurring in AMD .2), to photoreceptors from serum ; h; h204]; 2O2 [2O2, by modulating the activity or the expression of the eNOS and iNOS isoforms [In a recent study, our group examined the effects of Aflibercept and Ranibizumab on oxidative stress in vitro on cultured ARPE-19 cells and showed that both agents  were positively involved in the modulation of cell viability and mitochondrial function in RPE cells, acting on mechanisms mediated by NO release and the regulation of autophagy both under physiologic conditions and after exposure to H2O2 . In partisoforms . For the2O2 [2O2 and modulated the activation and expression of eNOS and iNOS isoforms in RPE cells; moreover, the presence of a NOS inhibitor decreased the protective effects elicited by anti-VEGFs on RPE cells. Those findings further supported the hypothesis that NO might play an important role as a mediator of the protective effect of the anti-VEGFs on cellular survival [Contradictory evidence exists in the literature on the effects of anti-VEGFs on mitochondrial function; in fact, while Malik et al. did not find any beneficial effect on mitochondria at clinical doses  , Sheu et2O2 . The ressurvival .In the present review, we have highlighted the different pathways involved in the initiation of AMD and in the progression to the late stages of disease in the context of oxidative stress. A growing body of scientific evidence supports the hypothesis that oxidative damage plays a key role in the initiation of AMD pathologic processes, such as drusen formation and RPE changes, with secondary activation of the inflammatory cascade and of mechanisms of cell death. Moreover, the idea that oxidative stress is also directly involved in the process of neovascularization in the late stages of the disease is increasingly gaining ground between researchers. NO contributes to the regulation of choroidal perfusion and the imbalance between NO and RNS observed under pathologic conditions is thought to induce microcirculatory changes in the choroid, both in non-neovascular and nAMD. Anti-VEGF agents have been shown to act against oxidative damage and to have a protective effect on cellular survival by preserving mitochondrial function, the activation of the autophagy defense system and mechanisms mediated by the release of NO. Further research is needed to study new treatments or implement current treatments, with the purpose of better counteracting the damaging effect of oxidative and nitrosative stress in AMD.


This clear trend of ocean warming and acidification was documented in the fifth Assessment Report (AR5) by Intergovernmental Panel on Climate Change (IPCC). The warming of the surface ocean could increase stratification, suppress transport of nutrients into the upper photic zone and alter hydrographic properties or patterns of ocean circulation. The effects of OA include the changes of seawater carbonate chemistry such as an increase in partial pressure of seawater CO2 (pCO2) concentration and a decrease in calcium carbonate (CaCO3) saturation state  relative to pre-industrial times (1870–1899) . They discuss how these different compositions may highlight the different strategies of these two phytoplankton communities to cope with ongoing environmental changes in the Antarctic Ocean. Kang et al. demonstrate the differences in carbon uptake rates and intracellular biochemical compositions between two different size fractions of phytoplankton to understand the ecological roles of the small phytoplankton in terms of food quantity and quality in the East/Japan Sea where the water temperature has rapidly increased. Their findings show that the increase of small phytoplankton under the warming ocean conditions could negatively affect the primary productivity and caloric content, with further consequences on the marine food webs. The photosynthetic responses to oceanic physio-chemical conditions and phytoplankton communities in the oligotrophic Western Pacific Ocean were presented by Wei et al.. Their study found that the important biotic variables influencing Fv/Fm are diatoms, Prochlorococcus, and picoeukaryotes, whilst the maximum of primary production is closely related to cyanobacteria, dinoflagellates, and Synechococcus. The detailed investigation of a chromophytic phytoplankton community using high-throughput sequencing of rbcL genes in the Western Pacific Ocean was presented by Pujari et al.. The authors found that the diversity of RuBisCO encoding rbcL gene varies with depth and across latitudes in the Western Pacific Ocean. The variation observed in chromophytic phytoplankton suggests the strong influence of environmental variables on biological production induced by oceanographic features. Thangaraj et al. investigated comprehensive proteomic profiling of diatom Skeletonema dohrnii with a change of temperature and silicate deprivation based on the iTRAQ proteomic approach, to understand the effect of the temperature and nutrient on the physiology of marine diatoms growth and photosynthesis. Their study shows that the proteome analysis for environmental stress-response of diatoms could extend our understanding for the potential impacts of climate change on the physiological adjustment to the metabolic process of phytoplankton. Sow et al. present a clear and concise description of the biogeography of Phaeocystis along a transect from the ice edge to the equator in the South Pacific Ocean, by way of high-throughput 18S rRNA gene sequencing. Their study shows that Phaeocystis could be occasionally highly abundant and diverse in the South Pacific Ocean, whereas the oceanic fronts could be the driving force for the distribution and structure of Phaeocystis assemblages in the ocean. Their work greatly expands our knowledge about the biodiversity patterns and abundances of Phaeocystis as a globally important nano-eukaryote.Out of the 10 works published, seven of them are focused on the phytoplankton communities, or single species of microalgae, or environmental drivers. Malits et al.. Their study demonstrates that the effect of OA on viral dynamics and viral-mediated mortality varies depending on the nutrient regime of the studied systems. It helps us to understand how viral-mediated mortality of microbes (VMMM) can be modified with environmental forcing. Another work looks into the contribution of grazers and viruses in controlling ecologically distinct prokaryotic sub-groups  and low nucleic acid (LNA) cells) along a cross-shore nutrient gradient in the northern South China Sea . Their study shows how the nutrient regime influences the fate of ecologically relevant prokaryotic groups in the actual context of global warming and the anticipated oligotrophication of the future ocean. Sörenson et al. address the resilience of a marine microbial community, cultivated in an outdoor photobioreactor, when exposed to a naturally occurring seasonal stress. Differential gene expression analyses suggest that community function at warm temperatures is based on concomitant utilization of inorganic and organic carbon assigned to autotrophs and heterotrophs, while at colder temperatures, the uptake of organic carbon was performed primarily by autotrophs. Overall, the microbial community maintains a similar level of diversity and function within and across autotrophic and heterotrophic levels, confirming the cross-scale resilience theory.Three of the 10 published works have focused on the response of viruses, prokaryotes or microbial communities to environmental stress. The response of viruses to two anthropogenic stressors (OA and eutrophication) was presented by The topics of the papers published in this Research Topic range from viruses, prokaryotes to phytoplankton and cover microbial communities from the various oceans. The studies confirm that the changes already occurring in ocean environments affect the metabolism and physiology of microbial communities, and further suggest that future changes will impact the physiological and ecological function or strategy of the microbial community in the marine ecosystem. Since most of these studies focus on the response of a single taxonomic population of microbes to environmental changes, our special issue highlights the need for studies to understand how ecological interactions occurring within and among the microbial community in the changing ocean will affect ecosystem structure and function. Finally, we hope that the group of papers that we have drawn together here will be a valuable addition to the accumulating observational evidence of how microbial communities are responding to the climate-related changes and consequently useful for evaluating and predicting the ongoing and future responses of marine ecosystems associated with the global climate change.MSY wrote the text with input from CL. All other authors commented on and approved the text.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


EmONC integration was reportedly high and significantly associated with EmONC training and availability of guidelines. However, the congruence of reported and actual extent of integration of EmONC at the three levels of healthcare delivery still need validation as such would account for the implementation success and maternal-neonatal outcomes.The integration of emergency obstetric and newborn care (EmONC) into maternal and newborn care is essential for its effectiveness to avert preventable maternal and newborn deaths in healthcare facilities. This study used a theory-oriented quantitative approach to document the reported extent of EmONC integration, and its relationship with EmONC training, guidelines availability and level of healthcare facility. A descriptive cross-sectional study was conducted among five hundred and five (505) healthcare providers and facility managers across the three levels of healthcare delivery. An adapted questionnaire from NoMad instrument was used to collect data on the integration of EmONC from the study participants. Ethical approval was obtained and informed consents taken from the participants. Both descriptive  and inferential analyses  were done with statistical significance level of p<0.05 using STATA 14. The mean age of respondents was 38.68±8.27. The results showed that the EmONC integration median score at the three levels of healthcare delivery was high (77 (IQR = 83–71)). The EmONC integration median score were 76 (IQR = 84–70), 76 (IQR = 80–68) and 78 (IQR = 84–74) in the primary, secondary and tertiary healthcare facilities respectively. Integration of EmONC was highest (83 (IQR = 87–78)) among healthcare providers who had EmONC training and also had EmONC guidelines made available to them. There were significant differences in EmONC integration at the three levels of healthcare delivery ( Maternal and newborn morbidity and mortality is a worldwide health challenge with burden disproportionately distributed and highest in developing countries. The 2015 estimates of global maternal and neonatal mortality documented 303,000 maternal deaths, 2.6 million stillbirths and 2.7 million newborn deaths, most of which happened in developing nations especially Sub-Saharan Africa [Obstetric complications such as haemorrhage, sepsis, eclampsia, obstructed labour and fetal distress remain the leading cause of deaths in women of reproductive age and neonates in low and middle-income countries. These deaths are preventable with implementation of emergency obstetric and neonatal care (EmONC) to treat and manage the obstetric complications in healthcare facilities –8. The NNigeria as a nation has adopted EmONC as an evidence-based practice to be implemented in healthcare facilities to reduce maternal and neonatal morbidity and mortality, yet only 1.2% and 3.9% of public healthcare facilities fulfil the criteria for BEmONC and CEmONC respectively . NtambueIntegration of EmONC is necessary for EmONC effectiveness to avert maternal and newborn deaths that result from obstetric complications. Integration is an implementation outcome that focuses on the extent to which an intervention has truly and in reality become part of work in services or organization . EvidencWhile EmONC is not a newly adopted intervention in Nigeria, the anticipated result has not been realised. This is evident in the country’s maternal and mortality ratio of 814 /100,000 deaths and neonatal mortality ratio of 34/1,000 births . There iAssessing integration on an established framework of normalization process theory offers the opportunity for comparability and ensures generalizability of knowledge from various local context . To a laThis is a descriptive cross-sectional study conducted at the three levels of healthcare delivery system in Osun State, Nigeria. Osun State is one of the 36 states in Nigeria. The state has three senatorial districts, six administrative zones and thirty Local Government Areas (LGAs). A purposive sampling technique was used to select nine of the thirty LGAs . Also, four primary healthcare facilities in each of the six LGAs where State hospitals are located were selected. Therefore, a total of 33 health facilities  were selected based on World Health Organisation framework of linking one CEmONC healthcare facility to four BEmONC healthcare facilities . All 505In Integration was highest at the tertiary healthcare facilities with a median score of 78 and narrowest total variation. The extent of EmONC integration at primary and secondary healthcare facilities was the same (76) although primary healthcare facilities had a wider total variation.In Implementation research assessing the integration of EmONC is important in bridging the gap between the evidence of EmONC effectiveness and its real-world practice. The integration of evidence-based practice is dependent on the collective and coordinated behaviour of health professionals within the complex healthcare system . IntegraThe study was carried out among five hundred and five (505) healthcare providers and facility managers in primary, secondary and tertiary healthcare facilities in Osun State. The categories of healthcare providers in this study were the nursing staff (nurses/midwives), medical practitioners, and community health extension workers (CHEWs). More than half of the respondents were working in primary healthcare facilities. The World Health Organisation recommendation to link four basic EmONC healthcare facilities  to one comprehensive EmONC healthcare facilities  necessitA review of the minimum standards for primary healthcare shows basic emergency obstetric care should be provided for women with obstetric complications by a medical officer (where available) and nurse/midwife, while newborn resuscitation should be provided by a medical officer, nurses/midwife, CHO and CHEW . The staA careful comparison of the mechanisms of integration across the three levels of healthcare delivery shows there was a difference in the mechanism of integration between primary, secondary and tertiary healthcare facilities. The findings of the study reveal that there was a difference in coherence and cognitive participation across the three levels of healthcare delivery. This finding implies that the stakeholders’  understanding of the tasks that the implementation of EmONC requires of them and involvement in EmONC differs across the primary, secondary and tertiary healthcare facilities. This finding is expected as healthcare providers in primary healthcare facilities provide BEmONC while those in secondary and tertiary healthcare facilities provide both BEmONC and CEmONC . On the The findings established that EmONC has not been fully integrated into maternal and newborn care at all levels of healthcare delivery in the state. The results show there was a difference in the level of integration across primary, secondary and tertiary healthcare facilities. Integration of EmONC is higher in the tertiary healthcare facilities than in primary and secondary healthcare facilities. The tertiary healthcare facilities are referral centres with multidisciplinary experts in obstetrics care and management of complications. However, there is minimal collective action for EmONC integration at all levels of health care delivery as the findings of the study suggest sufficient training is not provided to staff for the implementation of EmONC, sufficient resources are not available and management does not adequately support EmONC implementation at all levels of healthcare delivery. Previous studies in Nigeria affirmed that the quality of EmONC is poor ,18 and eThe integration of EmONC at the healthcare facilities was associated with EmONC training and availability of EmONC guidelines in the maternity units. Majority of respondents in the primary and secondary healthcare facilities did not have training in EmONC nor have guidelines available in the maternity unit where they work. Healthcare providers who have been trained on the implementation of EmONC and also have access to EmONC guidelines are more likely to higher integration than those without training and guidelines. Lack of training and unavailability of guidelines may impact negatively on the knowledge, skills and confidence of healthcare providers to implement EmONC. Previous studies conducted in Nigeria documented poor knowledge and skills of health care providers ,36 whichThough EmONC integration seems to be high in all the healthcare facilities, it may be related to the fact that the study was done in public healthcare facilities where full MNC such as antenatal, intranatal and postnatal care are implemented. This was necessary to ensure that respondents have practical experience of care for obstetric complications as this study was part of a larger study on implementation of EmONC. So, exclusion of public healthcare facilities that only offer partial MNC might have contributed to the high EmONC integration among healthcare providers in this study. Also, this was a reported integration, and may not have reflected the actual integration of EmONC in the healthcare facilities. A complementary qualitative approach would be necessary to validate the high integration reported in this study.The state of maternal and newborn health as well as the high maternal and newborn mortality in Nigeria posed a query on the high EmONC integration and the authenticity of the information given by the respondents. Evidence has shown that the inability to implement effective interventions in healthcare facilities occurs because such interventions are not integrated into existing programmes . The impConsidering the items in the mechanism of integration, many of the healthcare providers concluded the management of the hospitals were not supportive enough with regards to EmONC implementation. The lack of training and guidelines as widely reported in this study as well as insufficient resources to implement EmONC is a clog in the wheels of successful implementation of EmONC in healthcare facilities. Diffin et al. noted that interventions are likely to be successfully implemented if there is an opportunity to implement them . Lack ofIt needs to be mentioned that the assumption that services at the primary care levels do not have to be provided by practitioners with desirable competencies that can assure better access to quality EmONC and MNC as operational in many public healthcare settings in Nigeria has negative consequences for healthcare access to clients and undesirable congestions at the secondary and tertiary levels of care. One critical observation by the investigators in this study is the lack of monitoring, evaluation and communication strategies in the implementation of EmONC. This would also need to be given due attention and further investigations.Integration of emergency obstetric and newborn care in maternal and child care has been sparsely studied. This study is one of the pioneering studies assessing the implementation process of EmONC in the context of its integration on an established framework of normalization process theory. Although the quantitative approach may not give the full picture of the reality of integration of EmONC in healthcare facilities, it provided valuable information on the dynamics of implementing complex interventions as it relates to mechanisms for cohesiveness and coordination of individuals involved in getting the interventions integrated in practice. The Normad instrument used has provided some pieces of information on the causes of poor quality of EmONC and where priority for improvement lies. This study had thus provided baseline information on the integration of EmONC using theory oriented quantitative approach with which future studies on EmONC could compare.The adoption of a theoretical approach for the integration of EmONC as shown in this study, may fail to capture the actual integration required in reality for the effectiveness of EmONC to reduce maternal and newborn mortality. Research on implementation of interventions and programmes in maternal and child health would benefit more from mixed methods research.There is a dearth of studies for comparison with the findings of this study. Efforts have been made by researchers to assess the integration of evidence-based interventions in well-established programs, though not in Nigeria ,25, but


The main difficulty of radiotherapy is to destroy cancer cells without depletion of healthy tissue. Stem cells and cancers are tightly interrelated. On the one hand, radiosensitivity/radioresistance of cancer stem cells affects the radiocurability of tumors, on the other hand, radiosensitivity is responsible for the stem cell depletion of organs at risk exposed to irradiation. Efficient solid cancer destruction is limited by the preservation of organ homeostasis. For this reason, targeted irradiation is an effective cancer therapy, however, damage inflicted to normal tissues surrounding the tumor may cause severe complications. The consequences of stem cell depletion of healthy tissue irradiated are acute and chronic radiation diseases. The depletion of endogenous stem cells can be compensated by a supply of exogenous stem cells. For this reason, cell therapy is a therapeutic approach that offers a therapeutic alternative to patients who have failed conventional treatment. This domain will bring forth the solution for optimal radiocurability associated with long-term patients’ quality of life.This special issue covers research on the radiosensitivity of cancer stem cells and adult stem cells associated with tissue regenerative medicine.Integration of the cross talk of these two types of stem cells is essential. Nagle and colleague studied the roles of organoids as model to understand relationship between normal tissue and tumor responses in radiobiological studies . UnderstThe consequence of restoring the homeostasis of healthy tissue is first of all to allow tissue regeneration and then organ functionality on a permanent basis. A supply of mesenchymal stromal cells (MSCs) ensures this functionality, mainly through a trophic effect. Two research articles dealt with MSCs in the treatment of radiological burns. Brunchukov and colleagues studied the effect of human MSCs derived from the placenta and their conditioned medium concentrate on skin-regenerative processes. The use of conditioned MSCs in severe local radiation injuries accelerates the transition of the healing process to the stage of regeneration and epithelization . CavalleEach pathology related to radiotherapy is complex, which is why it is necessary to apprehend all the elements of a pathology and its treatment but also to be able to understand in detail the associated mechanisms. Helissey and colleagues reviewed radiation cystitis and its treatments. The authors investigated the role of immunity with a special focus on macrophages. They concluded that MSCs seem to be an excellent therapeutic substitute for the treatment of fibrosis in chronic radiation cystitis .To go further into the abovementioned issue and end on an optimistic note, it is interesting to associate the beneficial effect of irradiation with cell therapy in order to propose novel treatments for new pathologies. Tovar and colleagues tried a therapeutic approach, based on MSCs stimulated with radiation, to improve pneumonia caused by SARS-CoV-2. The activation of the immune system by the irradiated tumor to trigger the beneficial abscopal effect is decisively improving radiotherapy applications and their outcomes .


Tool wear and breakage detection technologies are of vital importance for the development of automatic machining systems and improvement in machining quality and efficiency. The monitoring of integral spiral end milling cutters, however, has rarely been investigated due to their complex structures. In this paper, an image acquisition system and image processing methods are developed for the wear and breakage detection of milling cutters based on machine vision. The image acquisition system is composed of three light sources and two cameras mounted on a moving frame, which renders the system applicable in cutters of different dimensions and shapes. The images captured by the acquisition system are then preprocessed with denoising and contrast enhancing operations. The failure regions on the rake face, flank face and tool tip of the cutter are extracted with the Otsu thresholding method and the Markov Random Field image segmentation method afterwards. Eventually, the feasibility of the proposed image acquisition system and image processing methods is demonstrated through an experiment of titanium alloy machining. The proposed image acquisition system and image processing methods not only provide high quality detection of the integral spiral end milling cutter but can also be easily converted to detect other cutting systems with complex structures. Tool wear and breakage have a great effect on the quality of machined components and production efficiency. Lacking efficient detection methods of tool failure forms will lead to facture, large tolerance, and even damage of machine tools, resulting in great economic loss. Machine tools equipped with a tool condition detection system are found to have their downtime reduced by 75%, production efficiency enlarged by 10% to 60% and utilization ratio improved by more than 50% ,3. The rThe present tool failure form detection technologies fall into two categories: indirect and direct methods. The indirect methods determine the tool failure forms through the analysis of various signals generated in different cutting conditions η(k)=The optimal threshold The preprocessed and binarized images of a flank face are compared in It should be mentioned that the reflected light of the wear region cannot be perceived by the cameras and that the wear regions on the cutter are concealed in the background region. The wear region needs to be extracted with the images of the cutter both before and after machining. g status . SimilarThe image of rake face contains the wear region, background and cutter body under the point light source, the thresholding techniques that binarize the images are not applicable, instead, a Markov Random Field (MRF) image segmentation method is employed for the failure extraction of the rake face. The MRF model considers the spatial interaction of neighboring pixels; thus, spatial inhomogeneities in the images of the rake face can be processed with this model ,46,47,48Let us assume an image with pixel sites Since  theorem (14)U(Ω,rameters ,51. A coIn order to demonstrate the feasibility of the image acquisition system and abovementioned image processing methods, the detection of failure regions of the integral spiral end milling cutters is conducted during the machining process of titanium alloy.The experiment setup for machining test and failure detection is shown in The different images and extracted failure regions of the integral spiral end milling cutters are given in It can be concluded from In this paper, tool wear and breakage detection technologies based on machine vision were proposed for integral spiral end milling cutters. The spatial positions and type of cameras and light sources were designed to develop an image acquisition system which would capture high-quality images of rake face, flank face and tool tip of the milling cutters. Denoising and contrast enhancing were employed for the image preprocessing. Then, the failure regions in images of the flank face and tool tip were extracted after binarization by Otsu thresholding method, while the failure regions in images of the rake face were extracted after segmentation by MRF models. The feasibility of the proposed image acquisition system and image processing methods were eventually examined by the titanium alloy machining process. It was found that the failure regions on the cutters increased with the machining time. The cutters could be regarded as a failure when the failure regions reached their corresponding threshold values. The developed image acquisition system and proposed failure extraction methods provide reliable machine monitoring of the integral spiral end milling cutters during machining processes.


In daily inspection, the nonstandard management of sterile articles in clinical departments of hospitals often leads to the destruction of the sterilization effectiveness of sterile articles. Therefore, it is necessary to strengthen governance and improve this phenomenon. This study intends to investigate the mode in which the disinfection supply center participates in the supervision and management of the management of sterile items in clinical departments. It played a role in improving the standardization of the management of sterile articles in clinical departments and ensured the closed-loop management of the sterilization effectiveness of sterile articles.  Every quarter, the disinfection supply center of our hospital will inspect the standardized management of sterile articles in all clinical departments of the hospital, mainly including the storage environment and facilities of sterile articles, the cleanliness of storage cabinets, placement principles, whether they are stored by category, and the quality and validity management of sterile articles. The quarterly inspection results were summarized and analyzed to find the existing problems and the causes. The disinfection supply center shall supervise the improvement. After the disinfection supply center inspected the standardized management of sterile articles in all clinical departments of the hospital for the first time according to the inspection contents, under the guidance and assistance of the nursing department and the hospital infection department, it improved the sterile article management system, conducted knowledge training for the whole hospital, and incorporated the standardized management of clinical sterile articles into the quality control inspection of the nursing department. In the later stage, the disinfection supply center is responsible for conducting routine inspection and supervision on the standardized management of sterile articles in all clinical departments of the hospital every quarter according to the inspection contents, including summarizing, analyzing, and urging the clinical departments to achieve the improvement of the management of sterile articles in clinical departments. P < 0.05). The average number of lost packages caused by nonstandard management in the department was significantly reduced. The average rate of lost sterile packages during and after the improvement was significantly lower than that before the improvement . It also effectively reduced the cost caused by the loss of sterile packages.  The standardization of aseptic articles after improvement was significantly higher than before and during improvement, and the qualified rate was significantly different (99.4% vs 97.9% vs 89.5%,  The disinfection supply center participates in the quality control and management of sterile articles in the nursing department and regularly inspects and supervises the management of sterile articles in clinical departments. It can effectively improve the standardized management of sterile articles in clinical departments, ensure the safety of sterile articles, and form a closed loop of sterilization effectiveness. The disinfection supply center is one of the key departments of the hospital, an important department in nosocomial infection management  and an eThe Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine is a class III class a comprehensive hospital. 65 clinical departments use the sterilized articles of the disinfection supply center. Three senior nurses of the disinfection supply center conduct special inspections on the management of sterile articles in these departments, mainly routine standby sterile bags, special bags, and special sterile articles for emergency rescue, which are uniformly placed in the cabinet of the treatment room.According to the specifications for disinfection supply center and the on-the-job training course for hospital disinfection supply center, the inspection contents mainly include the following: (1) According to the expiration date, place them in an orderly manner from left to right, follow the principle of first-in, first-out, and take out the expired package in time. (2) The storage environment requires the temperature to be lower than 24°C and the humidity to be lower than 70%, sterile items are stored, the height from the ground is required to be ≥20 cm, the distance from the wall is ≥5 cm, and the distance from the ceiling is ≥50 cm. (3) Sterile items should be classified and stored in separate cabinets, and the storage cabinets should be kept clean and dry. (4) According to the needs of the department and the cost, determine the sterility of each department pack base and record. (5) The department is required to count the number of sterile packs every day and check the quality. If the outer packaging is loose and damaged, and the label is incomplete, take it out in time. From April to June 2018, the staff of the disinfection supply center inspected 65 clinical departments. The inspection mainly adopts the method of on-site assessment and hearing from the staff of the Inquiry Department. The inspection results are summarized and analyzed by the disinfection supply center and the nursing department. The main problems are shown in The nursing department incorporated the standardized management of clinical, sterile articles into the quality control inspection of the nursing department. The disinfection supply center is responsible for conducting routine inspection and supervising improvement according to the inspection contents every quarter. It was analyzed and discussed at each quality control meeting of the nursing department. Some departments carried out continuous quality improvement for the standardized management of sterile articles to urge the department managers to strengthen the standardized supervision of sterile articles.The head nurse of the disinfection and supply center gave standardized teaching and on-site training on the management of sterile articles to the head nurses of clinical departments and senior nurses of the whole hospital. They introduced the standardized operation of the management of sterile articles in the disinfection and supply center and the identification of sterilization effectiveness. Then, let the trainees return to the department for secondary training and popularize it to every staff member. The teaching and training contents mainly include the importance of storage and use of sterile articles, the necessity of overall arrangement of the base package, storage environment, facility requirements, placement and taking requirements, influencing factors, and other related knowledge. The relevant training contents were included in the theoretical examination of the nursing department to evaluate the learning effect of nursing staff. This measure enables the clinical department personnel to understand and improve the standardized management of sterile articles in theory and practice.The process started with the staff of the disinfection supply center, which set an example and strictly controlled sterile articles' quality. They ensured that the indication tape outside the sterilization package could be distributed to the clinical department only after it was discoloured and qualified. The process required the special frame to be sealed for transportation, strictly implemented hand hygiene when taking it, paid attention to the clean and dry placement position, and handled it gently to avoid damaging the packaging of the sterile package. In case of any problem, communicate with the clinical department in time and put forward any nonstandard operation. At the same time, the sterilization indication discoloration comparison card made by the disinfection supply center was distributed to the clinical department so that the clinical department staff could know the discoloration requirements of the indication card inside and outside the sterile package and make a good judgment.The disinfection supply center can improve the existing sterile article management system and refine the distribution and receiving process, and the hospital infection control department will assist in the audit. Finally, the nursing department can distribute the sterile article management system to all clinical departments for homogenization and implementation.During the rectification process, for the more prominent problems in each inspection, such as the inconsistency between the base number of sterile bags and the records, the on-site rectification shall be carried out immediately, and the importance of fixing the base number of sterile bags shall be emphasized again during the lecture. The actual number shall be consistent with the base number. If the base number is insufficient, the disinfection supply center shall be informed to increase it in time to facilitate overall arrangement and save hospital costs.During the year from July 2018 to June 2019, after the implementation of the measures, the disinfection supply center conducted routine supervision, summary and rectification on the management of sterile articles in the clinical departments of the whole hospital every quarter, four times in total, and timely put forward the nonstandard management of sterile articles in the clinical departments during the normal distribution process. According to the actual situation in the implementation of the inspection, the focus of the inspection content was appropriately adjusted, the inspection of the damage of the sterile package was strengthened, and the results of the four inspections under improvement were summarized so as to evaluate the feasibility of the supervision model of the disinfection supply center.After determining the feasibility of the supervision model of the disinfection supply center in the standardized management of sterile articles in clinical departments, with the assistance of the nursing department and the hospital feeling department, the disinfection supply center will continue to inspect the standardized management of sterile articles in clinical departments of the whole hospital every quarter, supervise and correct problems, and summarize and score at the same time. The special management of sterile articles was included in the quality control inspection of the nursing department. By summarizing the results of 8 inspections from July 2019 to June 2021, we can further evaluate the effect and significance of the supervision model of the disinfection supply center in the standardized management of sterile articles in clinical departments.Composition ratio = frequency of problems/total frequency of problems × 100%. Qualified rate of inspection results = total qualified frequency/total inspection frequency × 10%. Loss package rate = average number of lost packages/total number of single inspection packages × 100%. The loss value is the single loss value = the average number of lost packages × unit price.χ2 test, P < 0.05; the difference was statistically significant.SPSS22.0 was used for statistical analysis. The counting data were expressed in percentage and compared between groups Three training sessions were conducted for the clinical departments of the hospital. The number of participants and clinical departments are shown in During the rectification process from July 2018 to June 2019, the disinfection supply center was responsible for the statistics of the results of four rounds of quarterly inspection on the standardized management of sterile articles in 65 clinical departments of the hospital. The existing problems were less than those before the rectification, as shown in From July 2019 to September 2021, after rectification, the disinfection supply center was responsible for 8 rounds of standardized management of sterile articles in 65 clinical departments, and the quarterly inspection results were counted. The existing problems were less than those before and during the rectification, as shown in P < 0.05 in χ2 test, indicating the difference is statistically significant.The results of the standardized inspection of sterile articles in each clinical department were summarized and compared the qualification rates of the three processes, as shown in Table 6With the development of medical technology, the disinfection supply center has become an essential department for the hospital's development and a guarantee for sterile articles in the hospital. It provides cleaning, disinfection, sterilization, and disposable sterile articles for all hospital departments –8. ThereThe disinfection supply center is an important service department of clinical departments . While dTo sum up, the nursing department will incorporate the standardized management of the storage and use of sterile articles in clinical departments into the nursing quality inspection. By adopting the supervision and management mode of disinfection supply center, the disinfection supply center will regularly supervise the sterile articles in clinical departments, provide targeted training and on-site guidance to rectify existing problems, and strengthen the critical concept of standardized management of sterile articles by clinical medical staff. It ensures the closed-loop management of sterilization effectiveness of sterile articles and safe use which improve the standardized management and safe use of sterile articles in clinical departments. At the same time, it can also reduce the cost consumption caused by the loss of sterile packages.


Ablation of sites showing Purkinje activity is antiarrhythmic in some patients with idiopathic ventricular fibrillation (iVF). The mechanism for the therapeutic success of ablation is not fully understood. We propose that deeper penetrance of the Purkinje network allows faster activation of the ventricles and is proarrhythmic in the presence of steep repolarization gradients. Reduction of Purkinje penetrance, or its indirect reducing effect on apparent propagation velocity may be a therapeutic target in patients with iVF. Patients who have survived idiopathic ventricular fibrillation (iVF) are typically difficult to treat and often rely on an implanted Cardioverter Defibrillator (ICD) to restore normal heart rhythm . Single The cardiac Purkinje network is highly variable between species and within species, especially in the extent of the peripheral branches . The ven50, QRS duration at 50% of the QRS amplitude). We tested this in a computer model of a human heart and torso  predominantly through Purkinje-muscle conduction, and the other (in Purkinje-void tissue) predominantly through muscle-muscle conduction. Thus, the end of the QRS complex is generated by muscle-muscle conduction only. In the presence of a more penetrating Purkinje network, a relatively larger contribution of (fast) Purkinje-mediated conduction is expected at the beginning of the QRS complex, whereas the end of the QRS complex is relatively unaffected. We therefore reasoned that a Purkinje system that extends slightly more into the walls of the ventricles leads to a shorter QRS “body”  as an expression of relatively late activated tissue. This generates the question whether humans with a short QRS50 are more at risk for idiopathic ventricular re-entrant arrhythmias  block and not the maintenance of the arrhythmia.We have demonstrated earlier that conduction may modulate the arrhythmogenic substrate formed by a repolarization heterogeneity and may either promote or suppress the induction of reentry by a premature beat depending on the site of application of sodium channel blockade relative to a repolarization gradient . ConductEarlier studies have shown that fast activation of the heart, and shortening of the QRS duration, relates to the extensiveness of the Purkinje system . Our comWhether the Purkinje system indeed penetrates deeper into the ventricular wall of patients with iVF is yet to be investigated. Evidence of the involvement of the Purkinje system with iVF was provided by Indirect evidence of the involvement of the Purkinje system in iVF comes from the observation that Purkinje spikes often precede premature beats that give rise to ventricular fibrillation in iVF patients. Ablation of sites showing Purkinje spikes is often antiarrhythmic . It is tIt cannot be excluded that ablation of sites showing Purkinje spikes reduces the fine network of the Purkinje fibers, which, in turn, reduces the anatomical substrate for reentry. The Purkinje network as substrate for reentry was already recognized by Although the above ideas are speculative and not substantiated by systematic studies, our findings suggest that cardiac conduction velocity has a safe upper limit in the presence of pre-existing repolarization heterogeneities. Moreover, the reduction of apparent propagation velocity by ablating parts of the Purkinje system may underlie the antiarrhythmic efficacy of this therapeutic approach. These contentions need to be tested clinically.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.RC and BB designed and wrote the manuscript. MP performed computer simulation and edited the manuscript. MHa, ND, MR, VM, MC, and MHo edited the manuscript. All authors contributed to the article and approved the submitted version.MC is part-time employed by Philips Research.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The main deficits of the available classifications of radical hysterectomy are the facts that they are based only on the lateral extension of resection, do not depend on the precise anatomy of parametrium and paracolpium and do not correlate with the tumour stage, size or infiltration in the vagina. This new suggested classification depends on the 3-dimentional concept of parametrium and paracolpium and the comprehensive description of the anatomy of parametrium, paracolpium and the pelvic autonomic nerve system. Each type in this classification tailored to the tumour stage according to FIGO- classification from 2018, taking into account the tumour size, localization and infiltration in the vaginal vault, which may make it the most suitable tool for planning and tailoring the surgery of radical hysterectomy.The current understanding of radical hysterectomy more is centered on the uterus and little is being discussed about the resection of the vaginal cuff and the paracolpium as an essential part of this procedure. This is because that the current classifications of radical hysterectomy are based only on the lateral extent of resection. This way is easier to be understood but does not reflect the anatomical and surgical conception of radical hysterectomy and the three-dimensional ways of tumour spreading, neither meet the need of adjusting the radicality according to the different stages of FIGO classification, which depends—at least in the early stages—on the tumour volume and the infiltration in the vagina (but not on the directly spread in the parametrium). The new classification presented in this paper does not base anymore on the lateral extent of resection only but too on the depth of resection in the small pelvic and the extent of the resected vaginal vault without or with its three-dimensional paracolpium. This classification takes into account the tumour size, stage, localization and infiltration in the vaginal vault and may offer the optimal tool to adjust and tailor the surgery according to these important variables. Even when the radical hysterectomy has a long tradition as the standard therapy for early cervical cancer, there are a lot of unmet needs regarding the optimal technique and the most effective and practical way of defining and tailoring the radicality according to the tumour size and infiltration in the vaginal vault. The most popular classifications of radical hysterectomy are based on the lateral extent of resection Tumours with a big volume but without macroscopic infiltration in the vaginal vault or obvious infiltration in parametrium/paracolpium : these tumours demand a resection of a longer vaginal vault to be able to close the vaginal cuff beneath  from the tumour to avoid any spelling of tumour cells and any contamination of the abdominal cavity. In these cases and because of the curved and anteflexed shape of the upper vagina, tumors with ventral localization demand the resection of longer vagina cuff comparing with tumors from the same size and stage but with dorsal localization .(2)Tumours infiltrating the vaginal wall with no obvious infiltration in parametrium/paracolpium : these tumours demand the resection of a longer vaginal vault with paracolpium (the blood supply and drain and the lymph drain of the upper 1/3 to ½ of the vagina) to be able to confirm or deny any tumour spread along with the vaginal vessels/lymph ways.Therefore, it is essential in our opinion to find a more suitable classification for radical hysterectomy, taking into account both situations affecting the radicality and challenging the tailoring of surgery in early-stage (resectable) cervical cancer:In both good operable situations, it is possible—and we have to say mandatory—to spare the pelvic autonomic nervous system to reduce the postoperative complications to the minimum ,5,6.The second problem in the popular classifications of radical hysterectomy is the arbitrary definition  of type B (Querleu–Morrow) or class II (Piver-Rutledge) radical hysterectomy as the resection of parametrium at midway/halfway, which does not correlate with tumour spread in parametrium (direct -continuous- tumour infiltration or affected lymph nodes in parametrium) and neglects the lymph nodes and ways lying at the distal part of the lateral parametrium. The continuous parametrial invasion occurs rarely, and the tumour spreading in the adjacent parametrium takes place mainly by tumour cell emboli and lymph node involvement . The assThis new classification of radical hysterectomy depends on the Cibula 3-dimentional concept of parametrium , MuallemThis classification is no longer based only on the lateral extent of resection but also on the depth of resection in the small pelvic and the extent of the resected vaginal vault without or with its three-dimensional paracolpium. The resected length of the vaginal vault has to be adjusted to the tumour size  or to the tumour infiltration in the vagina . This is the most crucial point by adjusting and tailoring the radicality during surgery for cervical cancers according to the tumour volume and spread. We think that the resection of all length of 3-dimentional parametrium, which it is nothing else than the lymph nodes, lymph vessels and the blood supply and drain of uterus/cervix, is essential to be performed in every FIGO-stage (up IA2) demanding a lymph node staging (Sentinel and/or lymph node dissection). Here, it is worth mentioning the contribution of Girardi  and BeneThis classification takes too into account the location of the cervical lesion in the cervix, which plays an important role in the surgical decision about the resected length of the vaginal vault during the radical hysterectomy. The classification distinguishes, therefore, between tumours locating on the ventral (anterior) and tumours locating on the dorsal (posterior) cervical lips in FIGO IB-stage. This is because of the fact that the resection of a longer vaginal wall ventrally, which is, of course, the case with tumours locating at the ventral cervical lip , is anatThe radical hysterectomy has to be performed nerve sparingly in every procedure as long as there is no direct (contiguous) infiltration in the paracolpium and/or the tendinous arch of the pelvic fascia (endopelvic fascia).The three-dimensional anatomic template for the resection of parametrium and paracolpium depends on the precise anatomy of parametrium and paracolpium published before ,10 and bIn this way, every part of the three-dimentional parametrium and paracolpium has a proximal aspect  and a distal aspect . The dorsal parametrium in this classification is the sacrouterine ligament, and the dorsal paracolpium is the sacrovaginal ligament which has been previously described as the deep uterosacral ligament by Ramanah et al.  and as tThe ventral parametrium  is the vesicouterine ligament, and the ventral paracolpium  is the vesicovaginal ligament which contains the venal anastomoses between the vaginal vein and the inferior vesical vein  consisting from the lateral and medial vesicovaginal veins —Figure The detailed description of parametrium and paracolpium is shown in The new classification of radical hysterectomy describes four types of radical hysterectomy according to the clinical and surgical demands. Each type in this classification is tailored to the tumour stage according to the International Federation of Gynecology and Obstetrics (FIGO)- classification from 2018, taking into account the tumour size, localization and infiltration in the vaginal vault and depends on the precise three-dimensional anatomy of parametrium and paracolpium and their close anatomic relationships to the pelvic autonomic nerve system. The pelvic exentration or the extended resection of pelvic organs (Class V in Piver-classification or Type D in Querleu-Morrow classification) is no more a part of this classification because this kind of radical resection is rarely indicated for primary cases and is not compatible with the concept of radical hysterectomy.This procedure is equivalent to the so-called extra-fascial hysterectomy (Class A in Q-M classification) aiming to remove the entire uterus with parmetrium margins  and minimal vaginal vault. This tailored procedure is suitable for microscopic cervical cancers FIGO IA  and no lymphovascular space invasion (LVSI) .This procedure is equivalent to the Wertheim-Meigs Operation and included the resection of the distal aspects of the new defined ventral , lateral  and dorsal parametrium  but without paracolpium resection and with minimal (about 2 cm) vaginal vault, which will be the surgery of choice for stages IA with lymphovascular space invasion and IB1 (less than 2 cm) with dorsal localization .This procedure is similar to the class C1 radical hysterectomy in Q-M classification with complete resection of the upper defined ventral, lateral and dorsal parametrium but with resecting of only the proximal aspects 3-dimentional paracolpium allowing the resection of the longer vaginal vault (about 2–4 cm). This demands more preparation of the vagina and highlighting the vaginal vessels and the ventral parts of the inferior hypogastric plexus to be able to dissect them carefully, lateralizing and sparing them during the procedure. This type of radicality is the surgery of choice for stage IB1 with ventral localization, IB2 and IB3 with dorsal localization in the cervix. This new type of radical hysterectomy has the advantage of avoiding the difficult preparation and resection of the vesical venous plexus  and the vaginal vessels, which reduce the risk of injuring the inferior vesical vessels and the following ischemic injuries of the distal ureter and the bladder trigon. This type offers the opportunity to resect an adapted length of vaginal vault to cover big cervical tumours . It is wThis procedure is equivalent to the nerve-sparing Okabayashi operation (modified from Fujii) and included the radical hysterectomy with resection of the distal aspects of ventral , lateral  and dorsal parametrium  with the resection of distal aspects of ventral paracolpium , lateral paracolpium  and dorsal paracolpium (at the tendinous arch of the pelvic fascia) . This prIn the direct infiltration in paracolpium and/or in the endopelvic fascia, the ipsilateral resection of the inferior hypogastric plexus will be mandatory. This procedure is the surgery of choice for stage IB3 with ventral localization or deep stromal invasion, stage IIA and selected cases of stage IIB.The old classifications of radical hysterectomy depended only on the lateral extension of resection. This misinterpreted the concept of surgery to be reduced only on the resection of lateral parametrium with no or minimal resection of the ventral parametrium. The limited resection of the ventral parametrium and/or paracolpium restricted the length of the resected vaginal vault and made the surgery of tumours with big volumes (>2 cm) or with vaginal invasion pretty difficult.The new classification is based not only on the lateral extension of resection, but also on the depth of resection in the small pelvis, taking into account the three-dimensional parametrium and paracolpium template and the comprehensive description of the anatomy of parametrium, paracolpium and the pelvic autonomic nerve system . It takeThe author is aware that this new classification does not result from randomized control studies, but it depends on a clear described anatomical and surgical concept ,6,10 andThis new classification may supply a very good tool for uniting the terminology and definitions of radical hysterectomy and for planning the right tailored radical surgery for cervical cancer according to the tumour size, stage, localization and infiltration in the vaginal vault. All these parameters could be evaluated with clinical examination and with or without additional magnetic resonance imaging.The new suggested classification of radical hysterectomy does not depend only on the lateral extension of resection in lateral parametrium but consider the three-dimensional template of parametrial resection, the three-dimensional template of resection of paracolpium and the comprehensive description of the anatomy of parametrium, paracolpium and the pelvic autonomic nerve system. It may be a good tool for planning and tailoring the surgery according to the tumour size, stage, localization and infiltration in the vaginal vault.