It supports the assumption that imaging Mueller polarimetry holds promise for the fast and accurate collagen scoring in pregnancy and the assessment of the preterm birth risk.Preterm birth risk is associated with early softening of the uterine cervix in pregnancy due to the accelerated remodeling of collagen extracellular matrix. Studies of mice model of pregnancy were performed with an imaging Mueller polarimeter at different time points of pregnancy to find polarimetric parameters for collagen scoring. Mueller matrix images of the unstained sections of mice uterine cervices were taken at day 6 and day 18 of 19-days gestation period and at different spatial locations through the cervices. The logarithmic decomposition of the recorded Mueller matrices mapped the depolarization, linear retardance, and azimuth of the optical axis of cervical tissue. These images highlighted both the inner structure of cervix and the arrangement of cervical collagen fibers confirmed by the second harmonic generation microscopy. The statistical analysis and two-Gaussians fit of the distributions of linear retardance and linear depolarization in the entire images of cervical tissue  quantified the randomization of collagen fibers alignment with gestation time. At day 18 the remodeling of cervical extracellular matrix of collagen was measurable at the external cervical os that is available for the direct optical observations  The accurate assessment of PTB risk is critical both to devise new treatment options as well as for the deployment of the available intervention focused on prolongating the pregnancy, such as cervical cerclage, pessaries, or special drug administration.Preterm birth (PTB) is a public health problem worldwide. PTB complications are the most important cause of death in neonatal infants, and many survivors will face long-term health challenges2. Several studies suggest that the evolution of mechanical properties of cervical tissue in pregnancy is related to cervix softening because of cervical ECM remodeling4.The two main functions of uterine cervix in pregnancy include: (1) maintain its load bearing capability and integrity in the first phase of pregnancy, thus, letting a fetus to develop properly until delivery time and (2) prepare to labor and delivery by cervical tissue softening through physical and chemical changes that are part of the cervix ripening process and will let the cervix dilate during delivery. The main constituent of the extracellular matrix (ECM) of cervical tissue is fibrillar collagen6 leading to premature delivery. The early detection of the PTB risk may prevent this event and decrease both mortality and morbidity in infants as well as lowering health care system expenditures.All steps of the uterine cervix remodeling process are drastically accelerated in preterm labor8. Despite the extensive preclinical studies11 there are no clinical tools available for the fast and accurate detection of a spontaneous PTB risk.The ultrasonographic examination of cervix and the test of fetal fibronectin may help to avoid unnecessary treatment in case of negative results, but these techniques are not used for the PTB screening in pregnant women because of the low accuracy13 suggests exploring optical polarization for the assessment of the remodeling of cervical ECM in pregnancy. The development of polarization sensitive optical techniques for the accurate, fast, and non-contact diagnosis of the PTB risk in clinical settings represents the real challenge, as these modalities have potential to revolutionize the current medical practice of PTB risk diagnosis. The most promising approach includes using the complete Mueller polarimetry16 combined with the state-of-the-art Mueller matrix decompositions and data processing algorithms20, because (i) Mueller matrix images of a sample contain information on all polarimetric properties 14 of a sample, contrary to the incomplete polarimetric techniques , and (2) imaging Mueller polarimetry does not require sample scanning, all 16 Mueller matrix images of the entire cervix can be imaged in a few seconds an one wavelength22. Using Mueller polarimetric system in a visible wavelength range for the PTB risk assessment is a natural and safe choice, because visible light is harmless for the patients. Preliminary in vivo polarimetric studies of human uterine cervix in reflection configuration22 revealed linear birefringence of healthy cervical tissue; however, the detailed studies are needed to relate the observed optical anisotropy to the state of collagen ECM of uterine cervix during the pregnancy. Hence, we unavoidably face the fundamental questions:Is optical polarization sensitive to the modifications of collagen arrangement in the uterine cervix during pregnancy?Could the polarimetric signature of cervical collagen rearrangement be detected early enough to serve as a predictive marker of PTB risk despite shallow penetration depth of visible light in tissue because of strong scattering?Our case study of mice model of pregnancy address these questions using the custom-built complete imaging Mueller polarimetric system23 operating in a visible wavelength range in transmission configuration.An extreme sensitivity of polarized light to the subtle alterations of the structural components of such complex object as biological tissue14. We focused our analysis on the images of the total linear retardance Thin unstained sections of the upper and lower parts of the mouse uterine cervix from mice model of normal pregnancy at days 6 and 18 of a 19-days gestation period were imaged with the Mueller matrix polarimeter in transmission configuration. The experimentally recorded Mueller matrices were processed with the logarithmic Mueller matrix decomposition (LMMD) to obtain the images of polarization and depolarization parameters24  are shown in Fig. The total linear retardance images of the sections from upper and lower parts of the cervix (day 6) demonstrate circular arrangement of the collagen fibers in a midstroma around cervical canal  compared to the signals of ultrasound and MRI modalities36 or pathological zones40 that are not visible in the unpolarized intensity images. An imaging Mueller polarimeter integrates the signal over the volume of the probed tissue. This volume is defined by the thickness of tissue slab when measurements are performed in transmission configuration and by light signal penetration depth for the measurements in backscattering configuration. The latter is the most relevant optical measurement geometry for in vivo medical applications. Cervical ECM remodeling starts from the internal os towards the external os, the latter can be examined by a medical doctor during the colposcopy test41. The question arises – at which moment of pregnancy the ECM remodeling and consequent softening of cervix can be detected by an optical technique operating within the visible wave band (harmless for a patient) and having shallow penetration depth? Will the risk of PTB be detected early enough to allow for the deployment of necessary treatment to prevent PTB? The illustration of this problem is shown in Fig. It was shown that the wide-field imaging Mueller polarimetry in backscattering configuration provides high contrast images and highlights tissue microarchitectureThe images of tissue sections from both upper and lower parts of the mouse uterine cervix at day 18 of pregnancy are shown in the third and fourth columns of Figs. It confirms that the remodeling of ECM of collagen induced by cervix ripening can be detected with imaging Mueller polarimetry at least one day prior to delivery at day 19 in mice model of normal pregnancy.For the quantitative cervical collagen scoring during the course of pregnancy we conducted a statistical analysis of the distributions of the polarimetric parameters. The histograms of total linear retardance and linear depolarization in the images of the sections of lower part of mice cervices at days 6 and 18 of pregnancy are shown in Fig. The mean values of the total linear retardance are relatively small  and analyzed the distributions of all polarimetric parameters over the whole image, because such approach removes any operator-dependent bias in selecting the ROIs. In such case the parameters of circular statistics of the azimuth distribution show no significant difference between day 6 and day 18 of pregnancy, because the circularly arranged collagen fibers of midstroma at day 6 are covering the range of azimuth angles from 0 degrees to 360 degrees as well as the randomly distributed collagen fibers at day 18.The kurtosis of distribution of the azimuth of the optical axis was shown to be a promising metrics for the assessment of collagen arrangement in different zones of the cervix at different gestation time42.The polarimetric measurements of tissue in backscattering geometry will inevitably deal with the specular reflection of incident light on the uneven surface of tissue that will affect the backscattered signal. Such image pixels, however, can easily be detected and omitted from the analysis, because of a low depolarization of light specularly reflected by a surfaceThe suggested metrics for collagen scoring by the analysis of mean value, standard deviation, skewness and kurtosis of the distributions of retardance and depolarization in the images of cervical tissue as well as the parameters of fit with two Gaussian distributions do not require any image segmentation and selection of the special regions of interest for data analysis, and contain the valuable information on remodeling of the cervical ECM of collagen that may serve for the prediction of PTB risk.We have demonstrated the capability of a new promising polarimetric imaging technique, namely, imaging Mueller polarimetry operating in a visible wavelength range to detect the cervical ripening in mice model of normal pregnancy. We showed that cervical ripening starts from the internal os and progresses towards the external os of cervix. The state of cervical ECM remodeling is not detectable in the standard intensity images but is highly contrasted in the images of the total linear retardance and the azimuth of the optical axis. The circumferential arrangement of midstroma collagen around the cervical canal and subepithelial stroma zone was seen in the above mentioned images and confirmed by the SHG microscopy measurements.The polarimetric images of cervical tissue sections at day 18 confirmed the remodeling of cervical ECM throughout the entire cervix and, thus, complete ripening of mouse uterine cervix one day before delivery at day 19. As it was mentioned the PTB is characterized by the drastic acceleration of the normal process of cervix ripening. We demonstrated that the remodeling in cervical collagen affected the entire cervix at least one day before delivery in mice model of pregnancy. Hence, this remodeling can be detected with the imaging Mueller polarimetry in reflection geometry  as well, despite the fact that the penetration depth of Mueller polarimetry does not exceed couple of millimeters in cervical tissue in a visible wavelength range.17, and suggested collagen scoring metrics can be applied for the distributions of the retardance and depolarization values in the corresponding images of uterine cervix recorded in vivo.The most informative collagen scoring metrics include the statistics on the total linear retardance and the linear depolarization images of cervical tissue that were calculated with the logarithmic decomposition of the recorded Mueller matrices. Various Mueller matrix decompositions are available for the matrices recorded in backscattering configurationin vivo assessment of the PTB risk in humans during the colposcopy test22.Whereas the mouse reproductive system is different from that of human, the evolution of ECM of cervix during pregnancy in mice is representative of the same process in humans, but with a shorter time scale. It supports our assumption that Mueller polarimetry has potential to become a technique of choice for the fast, accurate and non-contact cervical collagen scoring and quantitative The mouse strain C57BL6/129sv mice were used and pregnant females in this study were between 3-6 months of age. For timed pregnancies, breeding pairs were set up in the morning for 6 hours. The presence of a vaginal plug at the end of the 6 hours period was considered day 0 of pregnancy. The birth of pups generally occurred in the early morning on day 19.Mice were housed in an approved animal resource facility. All animal procedures were performed in accordance with the standards of humane animal care following the NIH Guide for the Care and Use of Laboratory Animals. The research protocols were reviewed and approved by the Institutional Animal Care and Use Committee at the University of Texas Southwestern Medical Center (registration number: IACUC 2016-101519) and at Florida International University (registration number: IACUC-20-014). All animals were maintained and used in accordance with the ARRIVE guidelines.45. The mouse uterine cervix consists of the connective tissue mainly. It has a cylindrical shape, and there is an inner cervical canal that connects both the uterus and vagina . A cryostat (Leica CM3050) was used for the transverse cryosectioning of the whole length of cervix  were performed to calculate sixteen coefficients of a sample Mueller matrix for each image pixel. Non-linear SHG microscopy images were obtained with the SAMMM system24.The custom-built liquid crystal-based Mueller polarimetric imaging systemon Figs. a and 9b.47. Among all algorithms a logarithmic decomposition LMMD developed for the transmission measurements considers all optical properties as continuously distributed through the volume of a medium along the path length of probing beam. It makes LMMD particularly suitable for the studies of biological tissues. The key steps of LMMD are briefly recalled below. Within the framework of differential matrix formalism of a fluctuating anisotropic medium51 the transmission Mueller matrix is described by the following equation:z, is associated with a unique differential matrix m can be decomposed into a sum of matrices 52z. Spatial averaging is performed in the transverse plane to the direction of light propagation. It follows from Eq. (Several algorithms of nonlinear data compression were proposed for the physical interpretation of Mueller matrix dataTo obtain the differential matrix m of Eq.  at \docuz, the following relations hold23:A and B are the coefficients that do not depend directly on a local thickness of sample. It follows from the Beer-Lambert law that I - an intensity of transmitted light, z is physical thickness of a sample. Consequently, the ratio of the parameters described below should not depend directly on a local thickness z:A, and B parameters may vary within the The optical anisotropy, scattering and absorption properties of tissue as well as the path length of the detected light beam that travelled through tissue will all affect the measured values of tissue polarization and depolarization parameters. When a thin tissue section is measured in transmission the path length of the detected light beam is equivalent to sample thickness. Thus, the thickness of tissue section will also impact the polarization and depolarization parameters calculated with LMMD from the experimental Mueller matrices. We suggest mitigating the spatial fluctuations of thickness of tissue section in a transverse plane by exploring Eq.


To examine the impact of using Communty Treatment Orders (CTO) of the Mental Health Act on use of inpatient care in Assertive Outreach team.Currently there is little evidence of the efficacy of community treatment orders (CTOs), and in particular with patients who use the Assertive Outreach service. One large randomised controlled study found no impact on use of inpatient care while a naturalistc study found significant impact.Our primary outcome was the number of admissions with and without a CTO comparing each patient with themselves before CTO and under CTO(“mirror-image”). Our secondary outcomes were the number of bed days, and the percentage of missed community visits post-discharge. We also looked at the potential cost savings of a reduction in inpatient bed usage.All the 63 patients studied over period of 6 years had a severe and enduring mental illness. The use of a CTO was linked to a significant reduction in the number of admissions  and bed days  There was no significant difference in the percentage of missed community visits post-discharge. Looking at the costs, an average cost for an inpatient Assertive Outreach bed per day in the local Trust was £250, and there were 8145 bed days saved in total, making a potential saving of just over £2million, during the study period.This study suggests that the implementation of CTOs using clinical judgment and knowledge of patients can significantly reduce the bed usage of Assertive Outreach patients. The financial implications of CTOs need to be reviewed further, but this study does suggest that the implementation of CTOs is a cost-effective intervention and is economically advantageous to the local Trust.


However, we think the proposed approach is still reductionistic in its scope resulting in various problems as far as it concerns the development of adaptive and flexible police officers.Koedijk et al. recently proposed a step-by-step methodology for police organizations to develop an observational behavior assessment instrument to assess psychological competencies of police officers in a meaningful way. We strongly appreciate widening the scope of the assessment of psychological competencies beyond the pure measurements of constructs Koedijk et al. build their assessment approach on the assumption that police officers need to develop a certain level of competence, that can then be evaluated through observable competencies. While broadly competence refers to the practitioner's integrated skills . Instead, emphasis has to be put on the thinking and decision-making process underlying these behaviors. In this way, a focus on the thinking process aids the development of declarative over procedural knowledge (Cruickshank et al., Police organizations neglecting the underlying thinking processes when assessing observed behavior may nurture problematic aspects concerning the training and education of police officers (Koerner and Staller, police officers training for the test instead for performance in the field by focusing on the desired output instead of the underlying production process of any behavioral solution,police trainers focusing on the to be shown competencies, thus neglecting a focus on problem-solving processes of their learners, anda neglection in the development and assessment of individual solutions to problems, that emerge as a result of the individual problem-solving process.Taken together, we would like to encourage the authors—and police organizations—to refrain from a competence-oriented approach, that underlies the conceptualization of the proposed assessment (Fouad et al., MS and SK authors contributed equally to the ideas presented. MS wrote the first draft of the paper. Both authors contributed equally to editing the first draft to its final version.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.


Although many outstanding research challenges remain to be addressed, the successfuldevelopment of new treatments to preserve female fertility for a range of clinical indicationshas largely been underpinned by the conduct of extensive, fundamental research on oocytesand ovarian tissues from a number of laboratory and commercially important farm species.Indeed, the most recent evidence from large animals suggests that it is also possible to cryopreserveintact whole ovaries along with their supporting vasculature for later auto-transplantationand restoration of natural fertility. This review will explore how the methods developedto preserve human oocytes and ovarian tissues can now be used strategically to support thedevelopment of conservation strategies aimed at safeguarding the genetic diversity of commerciallyimportant domestic animals and also of preserving the female germplasm for wild animals andendangered species.A detailed understanding of the cryobiology of gametes and complex tissues has led to the developmentof methods that facilitate the successful low temperature banking of isolated mature humanoocytes, or immature oocytes  In the last few decades, advances in cryobiology have been combined with the development of newassisted reproduction technologies (ARTs) and used as a means to cryopreserve the structuralintegrity and biological function of key reproductive cells. Translation of these researchadvances has resulted in the development of the capacity to cryopreserve and long-term storeisolated gametes, embryos, complex gonadal tissues and even whole reproductive organs in humansand laboratory species as well as commercially important farm animal breeds and a limited numberof exotic or endangered species. Indeed, the issue of fertility preservation is particularlyrelevant in animals as over the last two decades, some 300 of 6000 farm animal breeds have becomeextinct and a further 1350 domestic breeds are being threatened with extinction as a result ofaggressive animal breeding strategies using limited genetic stocks of animals of high meritfor a range of economically valuable traits ; coolingto subzero temperatures; and either removal or conversion of the greater majority of liquidwater within the cells into a solid state. The reverse occurs during thawing or warming. Any ofthese elements can inflict damage on the cells to be preserved although the level and nature ofthe damage is dependent on the cryobiological properties of each individual cell type. Withregards to the cryopreservation of complex tissues containing multiple cell types, such asthe ovary, the success of cryopreservation is dependent on the need to balance the freezing optimafor a range of different cell types which are influenced by cell number and size and, in the caseof oocytes, maturational status, as well as the requirement to preserve the structural integrityof the tissue. Furthermore, the nature of the cryopreservation methodology, whether slow freezingor vitrification, the cooling and warming rates and the containment vessel used for tissue preservationand storage will all influence the efficacy of the preservation method and hence impact on thesubsequent viability of the preserved tissue. Finally, the unique biological properties ofoocytes challenge our potential to freeze-store these important cells. Mammalian oocytesare very large cells of approximately 120 µm diameter with a small surface area to volumeratio and high lipid and water content. The latter confers a high sensitivity to chilling injuryand intracellular ice formation. In MII oocytes these parameters are further confounded bythe presence of a fragile cytoskeleton that is resistant to the volumetric excursions commonlyassociated with equilibrium freezing and a highly temperature sensitive meiotic spindle apparatus. These et al., 2016). Regardless of species, it is clear that the success of oocyte cryopreservationis dependent on oocyte quality, a key parameter that is profoundly and negatively influencedby advancing maternal age  and Mexican gray wolf . Regardless of species,GV oocytes cryopreservation requires the freeze-storage of both the gamete and its supportingcompliment of cumulus granulosa cells. The success of GV oocyte cryopreservation is criticallydependent on the post-thaw/warming maintenance of the functional integrity of the heterologousgap junctional contacts connecting the cumulus cells to the oocyte. This network of cumuluscells supply the oocyte with vital nutrients and signaling molecules that are essential to drivethe cytoplasmic and nuclear maturation of the oocyte to the MII stage. Furthermore, cumuluscells have a discretely different cryopreservation optima compared to oocytes. The loss ofgap junctional contacts between the cumulus cell compartment and the GV oocyte is a common casualtyof the cryopreservation process such that both the capacity of the oocyte to under go in vitro maturation and its subsequent fertile potential and developmental competenceare severely compromised. Finally, GV oocyte preservation must be supported by the provisionof robust culture environments that support oocyte maturation in vitro. Insight into the discrete, species-specific differences in the composition of the cultureenvironment required to drive oocyte maturation will be needed to maximize oocyte quality aftercryopreservation.Some of the difficulties associated with the cryopreservation of MII oocytes may potentiallybe overcome by the preservation of fully grown, but nuclear immature, germinal vesicle (GV)staged oocytes. However, this option has proved inconsistent and like the MII oocyte preservationdetailed earlier, success rates appear to be influenced by species. In addition to rodent andruminants, successful GV oocyte vitrification has recently been reported in equids  following exposure to the ovotoxicimpact of chemotherapy agents for the treatment of cancer . When fertility preservation strategies require theremoval of the whole ovary and it is age appropriate to do so, ovarian cortex harvest and cryopreservationcan be most effectively combined with methods for in vitro maturation andvitrification of MII oocytes to maximize the likelihood of a future successful pregnancy outcomefor the patient. Although significant progress has been made in the development and use of ovariantissue cryopreservation as a means to safeguard the future fertility of girls and young womenat risk of POF, further optimization of the cryopreservation and transplantation protocolsare likely to be beneficial as the longevity of ovarian autograft function following transplantremains unclear. The latter is likely to be determined by patient age at tissue harvest and bythe degree of follicle loss that results from ischaemia and reperfusion injury following ovariantissue transplantation. Importantly, further research is also needed to define and mitigateagainst any potential risk of reseeding cancer cells through the transplanted ovarian tissues of oocytes from the primordial follicle stage to maturityin the laboratory . To date the production of healthy,live offspring from primordial follicles has only been achieved in mice (in vitro, the subsequent fertile capacity of the in vitroderived oocytes and, ultimately, the efficiency of IVGM strategies for cryobanked tissueswill be species specific. Furthermore, it is likely that no single IVGM strategy will fit allspecies and IVGM strategies for rare or wild species will likely have to be used in conjunctionwith xenografting in order to realize the fertile potential of the stored germplasm.Multiphase culture strategies are being developed to support the complete oratory , sheep in situ within ovarian tissues or by the vitrificationof MII oocytes. The stage is now set to translate these clinical advances for animal conservationand to use them to develop comprehensive strategies that will not only safeguard the future geneticdiversity of commercially important domestic species but will also facilitate germplasm preservationfor animals at risk of extinction.In conclusion although many questions remain to be answered, considerable recent progressin cryobiology, reproductive science, and IVGM technology have led to therapeutic advancesin clinical ART that have significantly improved our ability to cryopreserve female fertilityby banking primordial oocytes


Caring is described as the innermost core of nursing which occurs in a relationship between the patient and the care provider. Although caring in nursing is associated with maintaining and strengthening of the patient’s sense of dignity and being a person, there seems to be a gap between caring theories in nursing, healthcare policies and caring for patients by professional nurses in primary health care clinics. Developing strategies that will facilitate effective caring for patients by professional nurses in primary health care clinics within an ethical and mindful manner became an area of focus in this study.To develop strategies to facilitate effective caring for patients by professional nurses in primary health care clinics in South Africa.Strategies were developed based on the conceptual framework developed in Phase 2, which was derived from synthesis of the results of Phase 1 of the previously conducted study and supported by literature. The conceptual framework reflects the survey list of Dickoff, James and Wiedenbach’s practice theory.Three strategies were developed: 1) facilitating maintaining of the empowering experiences; 2) facilitating addressing the disempowering experiences by professional nurses, and 3) facilitating addressing of the disempowering primary health care clinic systems.The developed strategies, being the proposed actions, procedures and behaviours, could facilitate effective caring for patients by professional nurses in primary health care clinics. Caring Science is based on the philosophy of Human Caring, a theory articulated by Watson as a foundational covenant to guide nursing as a discipline and profession  is considered as a fundamental component of the health transformation process in post-apartheid South Africa. The PHC approach’s strength is based on its response to the local needs of individuals, families and populations through a comprehensive, intersectoral approach that focuses on communities as the unit of intervention  Model  Empowering experiences in caring for patients, 2) Disempowering experiences in caring for patients and 3) Disempowering experiences with PHC clinic systems. Literature regarding: 1) facilitating maintaining of the empowering experiences, 2) facilitating addressing the disempowering experiences, 3) facilitating addressing of the disempowering PHC clinic systems were the guiding principles in developing the strategies. The strategies in this study entail proposed actions to be taken, behaviours to be adopted and procedures to be performed to facilitate effective caring for patients by professional nurses. The strategies also include a cluster of decisions to be taken to pursue the goal to facilitate effective caring for patients by professional nurses. The conceptual framework was developed from the researcher’s thinking map as the basis for developing strategies, reflecting the practice theory survey list of Dickoff, James and Wiedenbach :415–435.The conceptual framework in this study reflects the activities or the strategies undertaken by the nurse manager and professional nurses to facilitate effective caring for patients by professional nurses in PHC clinics. The objectives to be achieved, proposed actions to be taken and how the available resources will be used to achieve the goal of effective caring for patients by professional nurses were listed. The decisions regarding the procedures to be implemented and the behaviours to be adopted were also made. The conceptual framework enabled the researchers to interpret and link the study findings into practice and also served as a tool for connecting concepts to provide a context for interpreting the study findings. The questions of the survey list were as follows: Who is the agent?, Who is the recipient?, What is the context, What is the procedure or process?, What are the dynamics?, and What is the purpose or outcome?A brief outline of the six elements follows:Agent – Who performed the activity?The nurse manager is the agent who plays an active role in facilitating the process of professional nurses effectively caring for patients. The facilitative role focuses on maintaining empowering experiences and addressing disempowering experiences through a continuous interactive process that ensures engagement, support and empowers professional nurses by guiding them in realising the nursing goals. The nurse manager also plays a significant role in facilitating the implementation of activities that promote the delivery of effective caring for patients by professional nurses in accordance with the patients’ health needs.Recipient – Who was the recipient of the activity?The professional nurses are the recipients who receive guidance and support from the nurse manager on maintaining empowering experiences and addressing disempowering experiences whilst they actively engage themselves and play an active role in the facilitation and implementation of the process to facilitate effective caring for patients.Context – In what context was the activity performed?The context for this study is the PHC clinics rendering comprehensive PHC services to patients; the nurse manager and professional nurses caring for patients in PHC clinics. The nurse manager supports and often takes part in caring for patients, especially when the PHC clinics are too full, to off-load the heavy workload from the professional nurse.Procedure – What was the guiding procedure?The outline of the procedure in this study is to develop strategies to facilitate effective caring for patients by professional nurses in PHC clinics. The nurse manager, being the agent, performs the activities of the facilitation procedure in interaction with professional nurses. The professional nurses, are the recipients of the activities of the facilitation procedure, aimed towards the realisation of the outcome of the study.Dynamics – What was the energy source for the activity?The dynamics are the driving forces or motivation to provide effective caring for patients. The empowering and disempowering experiences encountered by the professional nurses and the patients in the PHC clinics motivate the nurse manager in facilitating effective caring for patients.Purpose/outcome – What was the purpose/end product of the activity?The nurse manager facilitates effective caring for patients by professional nurses through engagement, empowerment and support of professional nurses. The professional nurses provide effective caring for patients in PHC clinics.n = 10) to 20 (n = 20) different staff categories, whilst a few also open on Saturdays for half a day. As revealed by the findings in Phase 1 of the main study, these PHC clinics are faced with challenges such as shortage of medicines, staff and functional medical equipment.The setting of this study was the PHC clinics in Ekurhuleni, an area in the eastern part of Gauteng Province, South Africa. The PHC clinics provide comprehensive health care services such as maternal, child and reproductive health, human immunodeficiency virus, tuberculosis testing and treatment, screening and care for non-communicable diseases and treatment of common ailments through the DHS  maintaining of the empowering experiences by professional nurses, 2) addressing the disempowering experiences of professional nurses as well as 3) addressing of the disempowering PHC clinic systems were the guiding principles in developing the strategies. The developed strategies will guide and assist professional nurses in PHC clinics in utilising effective caring behaviours displayed as kindness, empathy, respect and helpfulness in caring for patients within an ethical, reflective and knowing framework behaviours. The developed strategies will also enable professional nurses to maintain the empowering experiences and address their disempowering experiences in this environment.


In the original version of this article, the given and family names of Christiane Dienhart were interchanged. The original article has been corrected.


In the last 10 years, we have experienced exceptional growth in the development of machine-learning-based (ML) algorithms for the analysis of different medical conditions and for developing clinical decision support systems. In particular, the availability of large datasets and the increasing complexity of both hardware and software systems have enabled the emergence of the new multidisciplinary field of computational neuroscience  models are increasingly used by scientific communities due to their higher accuracy and efficiency. Deep learning comprises different classes of algorithms that implements artificial neural networks with deep layers. These models have proved effectiveness in a wide range of applications since they can be used even with non-trivial relationships among the features of a predictive task and between the features and the outcomes. On the other hand, due to the high inner complexity of the algorithms, is often difficult to obtain insights into the workings of the deep learning models. Their “black-box” nature makes the models less trustworthy to physicians, thus hindering their expansion into real clinical settings  has emerged, which aims to provide new methodologies and algorithms to enhance transparency and reliability to both the decisions made by predictive algorithms and the contributions and importance of individual features to the outcome  for gender classification. They exploited information provided by graph architecture on functional connectivity networks by means of GNNs which comprise graph operations performed by deep neural networks and demonstrated that the gender classification method is able to effectively extrapolate state-of-the-art results by achieving high accuracy values. At the same time, the authors introduced an important mathematical formalization concerning the relationship between GNN and CNN. Based on this relationship, they used a saliency map visualization technique for CNN, i.e., the gradient-weighted class activation mapping (Grad-CAM) to visualize the important brain regions resulting from the classification task, overcoming the current limitation issue about the interpretability of the GNN architectures.Bučková et al.. The authors tested a deep convolutional neural network trained to identify biological gender from EEG recordings of a healthy cohort on another dataset of EEG data of 134 patients suffering from Major Depressive Disorder. In their work, they developed an explainable analysis to verify the discriminative power of beta-band power and test its effectiveness before and after the antidepressant treatment by highlithing the contribution of each electrode in order to clearly identify the final set of biomarkes.The gender classification task was also treated by Lopatina et al. where several XAI methods based on attribution maps (heatmaps) were used in conjunction with a CNN to both identify multiple sclerosis patients from 2D susceptibility-weighted imaging scans and highlight individual heatmaps indicating the contribution of a given voxel to the classification decision.The crucial role of XAI methods for clinical personalized analysis was explored in the work of Lombardi et al. also showed how to use local XAI algorithms to extract personalized information about the importance of several brain morphological descriptors extracted from the MRI scans of a healthy cohort of subjects for the prediction of the biological age. The authors presented an explainable DL framework to evaluate the accuracy of the models while achieving high interpretability of the contribution of each brain morphological feature to the final predicted age They introduced two metrics  to compare different XAI methods and quantitatively establish their reliability in order to choose the most suitable for the age prediction task.Varzandian et al. adopted the brain MRI scans of 1901 subjects to train a predictive model based on the apparent brain age and the chronological age to classify Alzheimer's disease patients. The authors developed a workflow to perform the regression and classification tasks maintaining the morphological semantics of the input space and providing a feature score to assess the specific contribution of each morphological region to the final outcome.Bae et al. focused their work on revealing misleading points that may arise from the pre-defined feature space. They used a DNN architecture to simulate four different problem scenarios such as the incorrect assessment of the feature selectivity, the use of features that act as confounding variables, the overestimation of the network feature representation and several misassumptions regarding the feature complexity.Finally, although the concept of interpretability has several implications, one of the most important regards the ability to understand also the errors and pitfalls of the ML and DL algorithms. In conclusion, all the works included in this Research Topic outline the potential effects of XAI techniques in different diagnostic scenarios and show how empirical studies could draw future directions for boosting XAI in real clinical applications.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.This work was supported in part by the research project Biomarcatori di connettività cerebrale da imaging multimodale per la diagnosi precoce e stadiazione personalizzata di malattie neurodegenerative con metodi avanzati di intelligenza artificiale in ambiente di calcolo distribuito (project code 928A7C98) within the Program Research for Innovation -REFIN funded by Regione Puglia  in the framework of the POR Puglia FESR FSE 2014-2020 Asse X - Azione 10.4.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. 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African American caregivers are often confronted with the complexities of caregiving through the lens of race and associated health disparities. The COVID-19 pandemic has both exacerbated the systemic disparities and deeply rooted inequities experienced by African Americans and laid bare their effects on the community of caregivers. The purpose of this project was to explore the experiences of African American dementia caregivers during the COVID-19 pandemic. Nineteen African American caregivers of persons living with dementia were recruited by primary investigators and community partners with purposeful sampling techniques to participate in semi-structured focus groups that were held April 2021. Four overarching themes were constructed during thematic analysis: social isolation, decreased well-being, the good and bad of telehealth, and challenges in fulfilling the caregiver role. Caregivers expressed that they became socially isolated from family and friends, which led to them becoming depressed and mentally strained. Several caregivers felt they could not carry out their caregiver duties due to the constraints surrounding the pandemic. The varying levels of interaction with and the comfort level of physicians utilizing telehealth led to caregivers having mixed reviews on the popularized service. The results of this study will be used to culturally adapt caregiving education courses and programs promoting mastery and competency during a pandemic. In preparations for future public health crises, healthcare professionals will be able to use the results of this study to address the specific needs and improve the experiences of African American dementia caregivers.


Inflammatory bowel diseases (IBDs) and irritable bowel syndrome (IBS) are associated with decreased quality of life and mental health problems. Among various approaches to supportive therapy that aims to improve mental health in affected individuals, vitamin D supplementation is considered to be an effective method which may also be beneficial in alleviating the symptoms during the course of IBDs and IBS. The aim of the present study was to conduct a systematic review of the literature presenting the data regarding the influence of vitamin D supplementation on mental health in adults with inflammatory and functional bowel diseases, including IBDs and IBS. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (Registration number CRD42020155779). A systematic search of the PubMed and Web of Science databases was performed, and the intervention studies published until September 2021 were included. The human studies eligible to be included in the review should have described any intervention involving vitamin D as a supplement in a group of adult patients suffering from IBDs and/or IBS and should have assessed any component of mental health, but studies presenting the effects of combined supplementation of multiple nutrients were excluded. After eliminating the duplicates, a total of 8514 records were screened and assessed independently by two researchers. Further evaluation was carried out on the basis of title, abstract, and full text. Finally, 10 studies (four for IBDs and six for IBS) were selected for the current systematic review, and their quality was assessed using the Newcastle–Ottawa Scale (NOS). The studies analyzed the influence of various doses of vitamin D on bowel diseases, compared the results of vitamin D supplementation with placebo, or administered specific doses of vitamin D to obtain the required level in the blood. Supplementation was performed for at least 6 weeks. The analyzed mental health outcomes mainly included disease-specific quality of life/quality of life, anxiety, and depression. The majority of studies  confirmed the positive effect of vitamin D supplementation on the mental health of IBD and IBS patients, which was proven by all research works evaluating anxiety and depression and by the majority of research works evaluating quality of life. Although the studies followed different dosage regimens and supplementation protocols, the positive influence of vitamin D on mental health was found to be consistent. The number of studies on patients suffering from ulcerative colitis and the availability of trials randomized against the placebo group was low in the current review, which is considered to be a limitation of the present study and could also reflect the final outcome of the analysis. The conducted systematic review established the positive effect of vitamin D supplementation on the mental health of IBD and IBS patients, but this result requires further investigation, particularly in relation to other mental health outcomes. Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are idiopathic intestinal disorders that are characterized by repetitive episodes of inflammation of the gastrointestinal tract, usually associated with bloody diarrhea, tenesmus, and abdominal pain, while the location of the disease and the thickness of the affected bowel wall differ in the diseased individuals . They arThe diagnostic problems in IBDs are mainly due to the lack of appropriate diagnostic tools to differentiate between UC and CD , as wellAs described above, the IBDs and IBS may influence the mental health of patients, and their mental health may further influence the somatic course of the disease, which is observed in both IBD  and IBS Among the various methods of supportive therapy that are known to positively impact the mental health of patients, nutrition is considered to be one of the promising and potential options to reduce the symptoms of depression, as demonstrated in the systematic review and meta-analysis by Firth et al.  and systOf the various dietary factors known to play a key role in alleviating mental health problems, vitamin D is one of the most effective components. The meta-analyses by Vellekkatt & Menon , ShafferTaking into consideration the above-described state of knowledge, the present study aimed to conduct a systematic review of the literature analyzing the influence of vitamin D supplementation on the mental health status of adults with inflammatory and functional bowel diseases, including IBDs and IBS.The systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines , based oThe studies eligible to be included in a systematic review of influence of vitamin D supplementation on mental health in adults with inflammatory and functional bowel diseases were ought to describe any intervention including any dose of vitamin D supplemented and the assessment of any component of mental health.(1)adult population studied;(2)patients with confirmed IBDs and/or IBS studied;(3)applied vitamin D dose defined within the study;(4)any component of mental health assessed within the study (assessed using either subjective or objective measurements).The following inclusion criteria were scheduled:(1)animal model studies;(2)studies conducted in populations with concurrent intellectual disabilities;(3)studies conducted in populations with concurrent eating disorders;(4)studies conducted in populations with concurrent neurological disorders, including Alzheimer’s disease, epilepsy, etc.;(5)conducted assessment of supplementation of multiple nutrients combined;(6)studies conducted in populations of mothers/children, analyzing the association between maternal vitamin D supplementation and the mental health of their offspring.The following exclusion criteria were scheduled:No other exclusion criteria, associated with the stage or course of disease, studied population, or country were scheduled.The detailed description of electronic search strategy is presented in After conducting an electronic search and identifying potentially eligible studies, the duplicates were removed and the studies were verified based on the previously planned inclusion and exclusion criteria. They were verified in three phases—on the basis of title, abstract, and full text. If the full text was not available, the corresponding author of the study was asked for the full text of their study. The assessment in each phase was conducted independently by two researchers, while the results of the searching were verified by comparison of their lists and if any disagreement appeared, it was consulted by third researcher.The detailed procedure of including studies is presented in (1)the basic characteristics of the studies and of the studied populations ;(2)the detailed characteristics of the patients studied ;(3)the detailed characteristics of the applied vitamin D supplementation intervention and mental health outcome ;(4)the observations and conclusions .The data extraction was conducted based on the standard procedure, while researchers extracted the following data:If any information was not available, the corresponding author of the study was asked about the details of their study (data marked in the systematic review as provided on request). The data were extracted independently by 2 researchers, while the extracted data were verified by comparison of their results and if any disagreement appeared, it was consulted by third researcher.The included studies were assessed in terms of the quality of the study, expressed as the risk of bias, as recommended by Cochrane . The NewThe basic characteristics of the studies and of the studied populations of IBD patients for the studies included to the systematic review ,33,34,35The detailed characteristics of the studied IBD patients for the studies included to the systematic review are presented in The detailed characteristics of the applied vitamin D supplementation intervention and mental health outcomes for the studies of the IBD patients included to the systematic review are presented in The basic characteristics of the studies and of the studied populations of IBS patients for the papers included in the systematic review ,39,40,41The detailed characteristics of the studied IBS patients for the papers included in the systematic review are presented in The detailed characteristics of the applied vitamin D supplementation intervention and mental health outcomes for the studies of the IBS patients included in the systematic review are presented in The summary of the observed association between vitamin D supplementation and mental health outcomes for the studies of the IBD and IBS patients included in the systematic review, accompanied by the NOS total score, is presented in The conducted systematic review confirmed the proposed hypothesis that vitamin D supplementation positively influences the mental health of bowel disease patients. Only one study did not support this positive influence , and allAs the majority of studies included in this systematic review assessed the disease-specific quality of life/quality of life, it can be confirmed that this mental health outcome is significantly associated with the disease course and symptoms, as revealed in both IBD  and IBS Moreover, it is of particular importance that two studies assessing the influence of vitamin D on anxiety and depression, in IBD  and IBS However, except for the mental health outcomes, for which the influence of vitamin D supplementation has been studied so far, there are some reports revealing that bowel diseases are also associated with other mental health outcomes, which include self-esteem , lonelinThe results indicate that vitamin D supplementation may be beneficial to alleviate the symptoms during the course of bowel disease ,26 and mIn spite of the fact that the conducted systematic review highlighted some novel observations for the betterment of IBD and IBS patients, some limitations of the study need to be acknowledged. The most important issue is the inclusion of a small number of studies, especially the small number of studies randomized against placebo, and that no studies randomized against a placebo representing the IBD population were included. Moreover, it should be emphasized that there is a risk of overlap in the results presented within the included studies, since two studies ,39 were The conducted systematic review confirmed the positive influence of vitamin D supplementation on the mental health of bowel disease patients, observed for both IBD and IBS. The majority of the studies supported the beneficial effect of vitamin D supplementation on the studied mental health outcomes, such as disease-specific quality of life/quality of life, anxiety, and depression. Though the studies adopted different vitamin D dosage regimens for varied periods of time, the general observation of positive effect on mental health is consistent. However, the limited number of studies selected for the review, especially for UC, must be considered as a limitation of the present analysis. The effect should be further studied in a larger sample of patients and on other mental health outcomes.


OBJECTIVES/GOALS: We describe here the implementation of a pilot Quality Improvement (QI) program in clinical research processes in order to facilitate translation from bench to community. This presentation will also discuss challenges encountered by the research teams during the implementation of QI activities. METHODS/STUDY POPULATION: Miami CTSI collaborated with University of Kansas’ CTSA to test the implementation of a QI program for clinical research processes. The program has a duration of 1 year and consists of multi-modal training and coaching sessions with different research teams. Six teams comprising of Principal investigators, clinical coordinators, and regulatory specialists participated in the program based in applied clinical microsystem theory science. Team coaches and teams worked together to assess current processes, test new and improved processes, and standardize and disseminate applicable best practices of the QI program. RESULTS/ANTICIPATED RESULTS: The implementation of QI activities in large clinical research settings poses numerous challenges for the research team. We will present survey results from the coaching sessions and follow on feedback from the different teams involved in the program to implement the QI activities. We will describe the modifications and adjustments made to the original conceptual framework of QI program in order for it to be applicable and feasible for the settings of the University of Miami. We will provide recommendations for other academic clinical research centers that are considering implementing a QI program. DISCUSSION/SIGNIFICANCE OF IMPACT: The successful adaptation of a QI process to implement in academic clinical research settings relies on early engagement of the institution leadership, careful selection of team members, as well as developing communication skills to enhance team dynamics as a clinical research unit.


The retention force of electronic connectors, in general one of the essential specification requirements, is defined as a maximum force of metallic terminals withdrawn out of the corresponding plastic housing. Accurate prediction of the retention force is an important issue in the connector design stage; however, it is not an easy task to accurately assess the retention force based on the authors’ knowledge. A finite element analysis is performed in conjunction with a self-coded user subroutine accounting for relaxation/creep behaviors of semi-crystalline thermoplastic polymers under various loading conditions in order to appraise the mechanical performance of the plastic base structure. Material parameters adopted in the constitutive model are evaluated by utilizing the automated design exploration and optimization commercial software. Applications of the developed subroutine with several damage criteria to assess retention forces of two electronic connectors were conducted. Retention forces predicted by utilizing the current constitutive model agreed fairly well with the associated experimental measurements. A dramatic improvement of the underestimation of the retention force based on the approach commonly adopted in the industry is also demonstrated here. Thermoplastic polymers are broadly used as engineering materials in modern industry, from automotive systems to electronic devices. An electronic connector, used for electrical signal transmission, is basically comprised of two major components, these being metallic terminals and a polymeric housing. Terminals are secured into the housing via the interference of barbs designed in the terminal and the polymeric structure by using a fixture. The retention force of the connector, defined as the peak force of the terminal withdrawn out of the associated housing, is required to be sufficient to prevent embedded terminals from being detached from the housing under relatively critical conditions such as shock and vibration. Accurate prediction of the retention force is thus an important issue, especially in the connector design stage. Nonetheless, it is generally known that the retention force is not easy to be appropriately estimated due to the complex mechanical responses and fracture mechanisms of thermoplastic polymers.In order to properly illustrate the dependence of time, strain rate, and temperature on stress-strain behaviors of thermoplastic polymers, various constitutive models were developed based on experimental observations. Colak  modifiedGearing and Anand  used theAcademic studies related to applications of the advanced constitutive model suitable for the thermoplastic materials to industrial products under practical operation conditions are not broadly reported, and there are even fewer research articles focusing on the assessment of the retention force of electronic connectors. The constitutive model proposed by Ayoub et al. , with vaIn order to examine the rate-dependent mechanical response of semi-crystalline polymers, a series of uniaxial compression tests for both polyamide 4T (PA4T) and liquid crystalline polymer (LCP) were conducted at different strain rates of 0.001 To further assess the appropriateness of the choice of damage criteria presented later, the strength of an injection-molded PA4T latch of DDR4 connector under multiaxial loading conditions was conducted, as shown in Two types of the electronic connector, PCIE (with a PA4T housing) and SSD (with a LCP housing) as shown in The constitutive model proposed by Ayoub et al.  is choseDeformation gradients of both intermolecular resistance and network resistance can be respectively decomposed into elastic and inelastic parts in a multiplicative manner.Furthermore, the stress–strain behavior of the network resistance is given by the eight-chain rubber model (Arruda and Boyce ).(14)TBThe users’ subroutine VUMAT, which accounts for the constitutive model mentioned above, is coded and the ABAQUS/Explicit  solver iFour developed damage criteria are examined to evaluate the failure of the polymeric materials. (a) Maximum principal strain criterion: A local region of the structure with maximum principal strain larger than a certain threshold Mechanical behaviors of the latch of DDR4 connector under the compression conditions as described in the previous section are numerically examined. Both the head and the metallic fixture are assumed to be rigid bodies since they are much stiffer than the polymeric latch. Four-node tetrahedron elements with reduced integration are assigned to the latch while a region enduring large deformation illustrated in an insert of Geometry models of PCIE and SSD connectors are reasonably simplified in the numerical analysis as shown in It should be noted that in the connector industry, based on the authors’ understanding, the polymeric housing is usually regarded as the simple isotropic elastic-plastic material for the retention force numerical analysis. Comparisons of the simulation results based on the modified VBO model and the isotropic elastic-plastic model will be presented in the next section.Numerical simulations of the latch of the DDR4 connector under rather complicated loading conditions with four damage criteria were then performed. For the sake of concise presentation, only the force-displacement responses subjected to the head based on the calculations with the damage accumulation criterion are shown in Insertion/withdrawal force histories with respect to the displacement based on the simulations with the damage accumulation criterion of PCIE and SSD connectors are shown in Mechanical behaviors of the engineering polymers PA4T and LCP were experimentally and numerically examined in the current study. The modified VBO model, which was suitable for the rate-dependent semi-crystalline polymeric materials with four damage criteria, was coded as the user subroutine implemented into the finite element analysis software. Numerous material parameters of the modified VBO model can be evaluated by fitting the stress-stain relationships of the specimen under the uniaxial compressive loading conditions at two distinct strain rates based on the simulations with those based on the experiments. By utilizing the strength investigation of the latch of the DDR4 connector, simulations can reasonably capture the mechanical response and give fair estimations of crack orientation compared with the experimental observations. Trends of the withdraw force-displacement relationships of PCIE and SSD connectors based on the modified VBO model with the damage accumulation criterion and the corresponding experiments are relatively similar, and simulated retention forces agree well with the measured ones, while the approach commonly adopted in the industry yields substantial underestimations. Applications of the current numerical procedures to evaluate mechanical responses of other polymeric components/products of interest could be promising in the future.


It is with great pleasure that we present this Research Topic dedicated to handling of transient metals and their function in the brain. Iron and copper are important co-factors for a number of enzymes in the brain, which are involved in multiple processes including neurotransmitter synthesis and myelin formation. Both shortage and excess of copper and iron will negatively influence brain function. The transport of copper and iron from peripheral circulation into the brain is strictly regulated and the concordantly protective blood-brain and blood-cerebrospinal fluid barriers have evolved to protect the brain's internal environment from unwanted exposure from the periphery. The sites for uptake and transport of copper and iron into the brain overlap, and the uptake mechanisms of the two metals significantly interact: Both iron deficiency and overload lead to altered copper homeostasis in the brain. Similarly, changes in dietary copper influences the cerebral iron homeostasis.For long the focus of research on copper and iron in the brain has had a mainstay on the significance of molecules in the brain using these metals as co-factors. Moreover, the understanding of transport of the metals through the blood-brain and blood-cerebrospinal fluid barriers and the understanding of the further handling of the metals inside the brain have received prioritizing from many research groups. Naturally, the possibility of nutritional deficiency caused by insufficient dietary supply of copper and iron has also gained interest, and attempts to delineate the impact of dietary insufficient on the brain, not at least the developing brain, are important topics that could aid in understanding periods during development where sufficient metal supply could be a highest importance.In 2015, we launched this Research Topic with the intention to provide a platform for presentation of research on the significance of copper and iron for the brain. This Research Topic mainly covers: (i) the genetics of proteins handling copper and iron in the brain, (ii) the expression and function of copper- and iron proteins in normal and pathological conditions; (iii) the clinic manifestations of dietary deficiencies in copper or iron; (iv) the clinic manifestation of genetic diseases leading to mishandling of copper and iron; (v) therapeutic aspects of handling dietary deficiencies, overloading pathologies, or conditions with genetic mutations in proteins related to copper and iron.Møller et al. show that protein variants encoded by ATP7A transcripts missing either exon 10 or exon 15 are not functional and not responsible for the so-called occipital horn syndrome (OHS) phenotype, a mild variant of Menkes disease with mutation in the ATP7A gene. Prior studies have shown that only minor copper dependent transcriptional regulation of the ATP7A and ATP7B genes are apparent. In agreement with lack of rapid transcriptional regulation, the study of Lenartowicz et al. shows that a high copper concentration pressure leads to cellular selection. Interestingly, normal cells encoding the ATP7A gene have selective growth advantages at high copper concentrations, whereas cells without functional ATP7A has selective growth advantage toward low copper concentrations. The review by Lenartowicz et al. reports on the Mottle mouse, which closely recapitulates the phenotype of Menkes disease and leads to multi-systemic copper metabolism disorder caused by mutations in the X-linked ATP7A gene. Lessons from studies in the Mottled mouse reveal that the ATP7A protein is expelling copper from certain cells including cells in the kidney, intestine, placenta and testis, and that deficiency in ATP7A function leads to excessive or even toxic amounts of copper in these tissues and at the same time lack of copper in other tissues. Fu et al. show in their study on the role of copper in the developing ventricular system in the rat, that copper levels increase as a function of age, and subventricular zone shows a different expression pattern of Cu-regulatory genes than seen in the choroid plexus. An age-related increase in the copper-binding protein MTs and a simultaneous decrease in Ctr1 may contribute to the high copper level in this neurogenesis active brain region. The review of Skjørringe et al. discusses the role of the divalent metal transporter 1 (DMT1) for handling iron transport at the blood-brain barrier (BBB). DMT1 is detectable in endosomes of brain capillary endothelial cells denoting the BBB. Iron uptake at the BBB occurs by means of transferrin-receptor mediated endocytosis followed by detachment of iron from transferrin inside the acidic compartment of the endosome. McCarthy and Kosman discuss the transendothelial trafficking of iron at the BBB by covering mechanisms by which brain endothelial cells take-up iron from the blood and by which they efflux this iron into the abluminal space mediated by ferroportin. They also cover the regulation of iron efflux into the brain by exocrine factors released from adjacent astrocyte-end feet, and how cytokines secreted by the endothelial cells conversely may regulate such glial signaling. Codazzi et al. reviews the mechanisms responsible for non-transferrin-bound iron (NTBI) entry in neurons and astrocytes and on how they can be modulated during synaptic activity, not at least under the influence of calcium permeable channels and DMT1. They also in-depth speculate how NBTI might have relevance for cellular iron homeostasis in both physiological and pathological conditions. Gajowiak et al., studied changes in iron metabolism in a mouse model of amyotrophic lateral sclerosis (ALS). They report that overexpression of mutated SOD1G93A leads to pathological changes in a skeletal muscle with deposits of iron.This research forum hence covers many important characteristics of metal biology in the brain, and the advances thereof included within this Research Topic indeed brings novelty to the understanding of how the neurons and glial cells handles copper and iron to enable the significance of these essential metals for the brain.LM and TM: summary of topic. Both authors contributed to the article and approved the submitted version.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.


This historical summary of the main aspects of the Barlow valve helps readers to understand the complexity of this pathoanatomical and functional disease and the best approach for successful surgery.58.See Article page Mitral valve repair is the gold standard in the surgery of degenerative mitral valve disease, a solidly established option supported by practice guidelinesThe Barlow valve still poses technical challenges to surgeons due to its multifaceted pathoanatomical presentation with bileaflet involvement with abnormally thickened leaflet tissue, gross involvement of the subvalvular apparatus, and annular dilatation.8Journal, Barlow and colleagues,In this issue of the Additional investigations showed that pathoanatomic changes in the form of annular abnormalities like disjunction should not be separated from the disease complex.Surgery of the Barlow valve aims at restoring competence, releasing leaflet tension, and achieving leaflet coaptation. Another issue is like in other repairs what may eventually happen with the left ventricleThis elegant and comprehensive historical review of Barlow and colleagues on the Barlow valve


Preparedness of residents in long-term care (LTC) exposed to disasters continues to warrant concern. Prior work by our research team highlights explicit evidence of the profound vulnerability of Florida nursing home (NH) residents exposed to Hurricane Irma in 2017. This research adds to our knowledge of the profound effect of disasters on long term care residents. This symposium will utilize mixed methodologies to discuss the varied effects of Hurricane Irma on vulnerable older adults residing in Florida NHs and Assisted Living communities (ALCs). Using a novel methodology for identifying a cohort of ALC residents, the first presentation will present the morbidity and mortality effects of Hurricane Irma on Florida ALC residents and identify high risk groups by health condition. The second presentation will document the effect of Hurricane Irma on NH Residents previously enrolled in Hospice and expound on the effect of the disaster on hospice enrollment after the storm. The third presentation will present qualitative results of interviews with ALC administrators highlighting the effect of the storm on both large and small ( <25 beds) facilities. The fourth presentation will address the issue of heat exposure in the days after Hurricane Irma and consider the preventative effect of generators on morbidity and mortality. Finally, a fifth presentation will examine NH staffing level variation in the days leading to the hurricane. To conclude, this symposium offers a multi-faceted view of a disaster’s effects on LTC residents across Florida, including novel data from the NH environment and lesser-examined ALCs.


This session provides insights into how the pandemic challenged the capabilities and ingenuity of the Older Americans Act (OAA) programs and the aging network and what it means for in-home and community aging services now and in the future. Speakers will include key aging network stakeholders, who will discuss the overnight evolution of programs serving often isolated older adults.


Variations in the upper limb arterial pattern are commonplace and necessitate complete familiarity for successful surgical and interventional procedures. Variance in the vascular tree may involve any part of the axis artery of the upper limb, including the axillary artery and brachial artery or its branches, in the form of radial and ulnar arteries, which eventually supply the hand via anastomosing arches.To study the peculiarities of the arterial pattern of the upper limb and to correlate them with embryological development.The entire arterial branching of forty-two upper limbs of formalin fixed adult human cadavers was examined during routine dissection for educational purposes, conducted over a 3-year period in the Department of Anatomy, Lady Hardinge Medical College, New Delhi.The study found: 1) One case in which a common trunk arose from the third part of the axillary artery, which immediately splayed into four branches (2.4%); 2) High division of the brachial artery into ulnar and radial arteries, in 3 cases (7.1%); 3) Pentafurcation of the brachial artery into ulnar, interosseus, radial, and radial recurrent arteries and a muscular twig to the brachioradialis in 1/42 cases (2.4%); 4) Incomplete Superficial Palmar arch in 3/42 cases (7.1%); and 5) Presence of a median artery in 2/42 case(4.8%)This study observed and described the varied arterial patterns of the upper limb and identified the various anomalous patterns, supplementing the surgeon’s armamentarium in various surgical procedures, thereby helping to prevent complications or failures of reconstructive surgeries, bypass angiography, and many similar procedures. The web of arterial patterns in the body has always been an enigma. Inconsistencies in the arterial pattern of the upper limb in both origin and distribution are the rule rather than an exception. The axillary artery (AA) is a direct continuation of the subclavian artery, extending from the outer border of the first rib to the lower border of the teres major and thereafter continuing as the brachial artery (BA) of the upper limb.This observational study was conducted with donated human cadavers meant for research work and teaching for first-year Bachelor of Medicine and Bachelor of Surgery undergraduates at the medical institution. Eight to nine embalmed cadavers are designated for dissection purpose in the research laboratory for each new academic year and, since the study was conducted over a 3-year time frame, 24 embalmed cadavers and a total of 42 upper limbs were included. Cadavers that were not appropriate were excluded from the study. The Local Government approved the ethical aspects and policy for conducting research studies and for teaching purpose on donated human bodies at the Department of Anatomy in the Government Medical institution. Informed written consent was also obtained at the time of body donation from the donors themselves or their relatives.Cunningham’s Manual of Practical AnatomyIn the present study on 42 upper limbs , the artIn one of the 42 cases, an extremely rare type of variation was seen involving the axillary artery . The fiSubscapular artery , supplying the latissimus dorsi muscle along with the thoracodorsal nerve  supplying the lateral thoracic wall especially the third and fourth intercostal areas including the respective serratus anterior muscle parts and mammary gland  gave rise to the usual anterior and posterior interosseus artery and a persistent median artery, which passed deep to the pronator teres and accompanied the median nerve.The superficial palmar arch (SPA), which is completed by a superficial palmar branch of the radial artery and infrequently by an arteria princeps pollicis or arteria radialis indices, was not evident in three out of 42 limbs. In these cases, there was no contribution from a superficial branch or any other branch from the radial artery and therefore an incomplete SPA was observed that was formed solely by the ulnar artery in the palm . A mediaDeviations of the upper limb arterial pattern from its anatomical norms have been frequently reported, which makes it even more essential to familiarize one with the possible patterns for successful surgical interventions.Several authors have reported an exceptional number of branches from the axillary artery varying from seven to eight branches to as many as five to eleven branches.A very close similarity to our finding of variant AA is presented in a case report on the tetrafurcation from the third part of the AA, where a common trunk gave origin to TDA, CSA, PCHA, and LTA, whereas, in our study the PCHA had a normal origin from the third part of the axillary artery and the common trunk gave rise to an auxiliary LTA and the TDA, in addition to the SSA branch itself, which divided into CSA and TDA.The SSA is known to supply the subscapularis muscle by giving off one collateral branch in 31.1% and two branches in 29.3%.In another study conducted on 40 cadavers, the LTA emerged from the SSAThe TDA defines the posterior boundary of axillary lymph node dissection and any derailment of its normal course can compromise oncology results in surgeries involving lymph node dissections. The presence of multiple TDA seen in our study renders isolation of the vascular pedicle for free flap transfer a perilous task and could result in postoperative complications or failure of the flap itself.There are considerable variations of the brachial artery (BA) documented in the literature. In the majority, the brachial artery, which is a continuation of the axillary artery, begins at the inferior border of the teres major and ends by bifurcating about a centimeter distal to the elbow joint into radial and ulnar arteries. The two main classifications of arterial arm variations include one in which a brachial artery is positioned anterior to the median nerve, described as the superficial brachial artery, while the other main anomaly involves doubling of the brachial artery into superficial and deep brachial arteries. The former is called the superficial brachial artery superior when it occurs at the median nerve roots in the axilla. Another version of the superficial brachial artery is positioned posterior to the median nerve, but ultimately travels anterior to the median nerve more distally in the arm.,In cases where the brachial artery is doubled or presents with high bifurcation of the vessel, the superficial and deep brachial artery reunite distally before eventually either dividing into radial and ulnar artery or continuing as only a radial or an ulnar artery, with or without collateral branches.Unlike in our case, trifurcation of the brachial artery has been documented in the literature, dividing into radial, ulnar, and superior collateral arteries;The brachial artery is reported to become compressed by the bicipital aponeurosis in athletes with hypertrophied muscles in the forearm, to the extent that it causes discomfort and even obliterates the radial pulse.In our study, one cadaver had a median artery (MA) that originated from the common interosseous artery and travelled deep to the pronator teres, supplying the brachioradialis and accompanying the median nerve. The median artery did not pass under the carpal tunnel. The RA and the MA ended in the musculature of the forearm, making no significant contribution to the hand. As a result, an incomplete superficial palmar arch with no participation from the radial artery was observed in the hand. It was further noted that the ulnar artery that was solely involved in the superficial palmar arch was highly tortuous. The tortuosity of the ulnar artery is explained due to involvement of the ulnar nerve as an occupational hazard in those who engage in constant hammering/vibrating actions and repetitive traumatic activities; a condition known as hypothenar hammer syndrome.-Unwanted vascular injuries can be circumvented during surgical and other interventional procedures if any vascular anomaly is delineated in advance by Doppler study or MRI with angiography. The thoracodorsal and circumflex scapular vessels are used as recipient sites for autologous microsurgical reconstructions with free flaps such as deep inferior epigastric artery perforator (DIEP) or profunda femoris artery perforator (PAP) flap procedures.,Due to long term patency and survival benefits, the radial artery is a versatile conduit for CAB (coronary artery bypass) and open radial artery harvesting reduces the risk of endothelial damage.Considering the plethora of clinical significance scenarios, it is imperative for clinicians to have a thorough knowledge of the normal and aberrant vessels in the branching pattern of the upper limb.The principal arteries anastomose and periarticular networks of capillaries emerge according to a temporal sequence; some paths that are initially functionally dominant subsequently regress. The anomalous patterns occur as differences in the mode and proximodistal level of branching, aberrant vessels anastomosing with principal vessels, and/or vessels forming unexpected neural, myological, or osteoligamentous relationships.In conclusion, understanding of the normal and variant patterns of the vascular system is imperative for a favorable postsurgical outcome when the surgeon is taking an on-table decision in vessel selection for reconstructive surgery. Rarer variations are encountered more frequently than anticipated. Therefore, having a thorough knowledge about the kinds of variants that exist might help to raise the level of suspicion and thus extend the reach of the safety net for preventing surgical catastrophes. The present study is intended to raise awareness in the minds of surgeons and radiologists alike about the variations of the arterial arrangement of the upper limb that could determine the outcomes of surgical and interventional procedures.


A 70-year-old patient with positive anamnesis of hypertension and arthritis, went to our observation for an asymptomatic localized lesion on the hard palate. The lesion has been present for about seven years and initially appeared as a slight swelling at the midline of the hard palate. He reported a slow and constant expansion but remained asymptomatic. The objective examination revealed poor oral hygiene conditions, previous periodontal disease and prosthetic and endodontic treatments. On the anterior third of the hard palate in a central position there were multiple pink rounded neoformations, the bigger of about 1 cm in diameter and of elastic consistency. The patient confirmed the habit of tapping the tip of the pen on the palate. Palpation of the laterocervical lymph nodes was negative. There was no leakage of liquid to compression.


The recent development of magnetic resonance-guided focused ultrasound highlights the clinical significance of the stereotactic surgery of the thalamus including deep brain stimulation (DBS). Essential tremor and parkinsonian tremor respond well to DBS of the ventral intermediate nucleus (Vim) of the thalamus   and subthalamus (downstairs).Above the plane containing the anterior commissure (AC) and posterior commissure (PC), the ventral motor nuclei of the thalamus are arrayed as Voa, Vop, and Vim from the rostral to caudal direction . The venft, ft are made up of the ansa lenticularis  and fasciculus lenticularis (fl). The al originates from the ventral globus pallidus interna (GPi). The al is ventral and medial of the subthalamic nucleus (STN) and makes a turn (ansa) to go over the STN. The fl originates from the dorsal GPi. The fl goes between the dorsal STN and ventral Zi, the field H2 of Forel (Forel H2). The al and fl go through the prerubral field H of Forel (Forel H) and merge to become the ft. The ft goes through field H1 of Forel (Forel H1) and then enters the Voa/Vop , (ii) rostal Zi, (iii) Forel H2 (including fl), and (iv) STN. The posterior subthalamic area (PSA) consists of the cZi and Raprl  for this research from Japan Society for the Promotion of Science.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.