Annals of Surgical Oncology, Mihaljevic and coauthors show the importance of patient-reported outcomes measures (PROM) in abdominal cancer surgery,In this issue of the Patient-reported outcome measures have emerged during the past decade as a powerful tool for directly capturing patients’ perspectives and stimulating their autonomy in the decision-care processes.3PROMs are an objective measurement tool, even if the outcome they quantify is somewhat subjective; they undergo a rigorous development and validation process in order to make them an objective tool, with reproducible results from which valid conclusions can be drawn.PROMs can help to attain a more adequate care of cancer survivors, whose needs often can go unrecognized and unsatisfied.3The relevance of the PROM approach in cancer arises from the strong evidence showing the significant physical and psychosocial consequences that cancer treatment can have on patients’ QOL. These sequelae can often go unrecognized by health care teams.Similar to most studies published on PROM and cancer care, Mihaljevic et al. found a lack of correlation between postoperative complications or death and any of the PROM items evaluated.The newly developed PRO-CTCAE and Computerised Adaptive Testing (CAT) EORTC quality of life questionnaire (QLQ-C30) tools tested in the study followed the same trend as the HRQoL tool used for evaluating quality of life after major abdominal cancer surgery in this group of patients. These results are encouraging, showing that new practical tools for estimating quality of life dimensions reported directly from the patients are available for surgical cancer patients.The digital patient-reported outcomes has some limitations that can be divided in four categories: ability to use PROMs, engagement, emotional distress, and technical barriers.The PATRONUS study conducted by Mihaljevic et al. is very welcome, because it delivers a strong message on the relevance of empowering the main players of academic medicine and clinical practice, i.e., students and patients. The CHIR-Net Sigma study group is composed of medical students interested in the generation of new knowledge to improve clinical care through studying the direct experience of patients, making patients the protagonists of their own care process.Empowerment of students and patients is the key common ingredient of the student-centered learning and patient-centered medicine approaches. Both of these have shown improved outcomes in medical education and medical care compared with traditional models.11The development of research competences have been considered a key dimension of excellence in medical education.


Panic buying (PB) is an emerging Research Topic. During this COVID-19 pandemic, it has got attention even though it has been noticed since a long time back during the crises . AlthougArafat et al.; Arafat et al.). We proposed a complex interaction between several factors mentioned as primary, secondary, and tertiary factors  . One study replicated the concept that assessed PB in Bangladesh both in COVID-19 and non-COVID-19 context . The study revealed that the PB events in Bangladesh were precipitated by adverse environmental stimuli; identified that the people buy staples; and describe the implemented prevention strategies . Another study from China assessed the relationship of scarce consumption behavior with materialism and the need to belong during public health emergencies . The study identified that the severity of the emergency event is positively associated with materialism, scarce consumption, and the need to belong even though the effect is transient . This phenomenon is also explained by the environmental stimuli and human psychology interaction model. During this COVID-19 pandemic, adherent, and dysfunctional safety behaviors mediate the consumption pattern . Mass mediaAs an issue, PB has got the recent attention of the academics and research community . It is d et al.) . As per Weismüller et al.). These factors also affect the PB behavior in several aspects and fit with the environmental stimuli and human psychology interaction model . It has also been explained from the perspective of certain behavioral and psychodynamic explanations (Cooper and Gordon). Supply restriction results in the generation of negative emotions in the consumers, which in turn result in PB behavior. Rajkumar, had attempted to explain the panic buying behavior from the perspective of the bio-psycho-social model. Biologically the panic buying behavior has a resemblance with the compulsive and hoarding phenomenon which might be due to shared neurobiological factors. Psychological explanation of panic buying might be explained on the basis of attachment to objects. The attachment becomes very crucial at the time of scarcity of the object. From the social perspective, panic buying can be understood. As per this, social exclusion and lack of social support are associated with excessive buying and stocking (Rajkumar). Group panic buying has also been reported during this COVID-19 pandemic. The propagation model to a greater extent explains the PB behavior . The spread of negative information (both on online platforms and offline forums) evokes panic among people, compelling them to panic buying . A study from the Iraqi Kurdistan region has revealed that lack of sensibility in social media posts may increase panic buying behavior . It has been seen that individuals who have more pandemic-related health fears and those who experience intense stress due to scarcity of products and restrictions in their availability are more likely to involve in panic buying (Georgiadou).communication and long-term trust in the government affect safety behaviors during public health emergencies  or a normative behavior in its extreme at the face of stress . This phenomenon is poorly studied in past; however; there is extensive research during this COVID-19 pandemic, to understand the phenomenon. The collection of this Research Topic still identifies that prevention of PB has got little attention despite being a common incidence during public health/environmental emergencies. More articles are coming out discussing the theoretical and phenomenological aspects whilst ignoring the prevention aspects. As PB is a closely related event of a public health emergency, prevention of PB should be considered as a regular package of emergency preparedness. Without the prevention of PB, the distressed people during public health emergencies wouldn't be benefitted. Then, all the scientific efforts would seem meaningless.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.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 angiosperms exhibit a wide range of variability in floral traits such as shape and size, flower color is a hallmark of angiosperm diversity. Since before Darwin's time, flower color has long been appreciated for its role in pollinator attraction  and Meconopsis cambrica (orange), and white and red varieties of Mandevilla sanderi. The authors found that the absorption spectrum (i.e. colour) of anthocyanins can be dependent on the pH of the vacuole, however, not all flavonoids respond similarly to changes in vacuolar pH. Color diversity is also remarkably high in Gesnerioideae and Ogutchen et al. have elegantly shown that this is due to the expanded use of the anthocyanin biosynthetic pathway. In this family, the anthocyanin biosynthetic pathway includes the deoxyanthocyanin branch, which is rarely functional in angiosperms. Ogutchen et al. also call for a better understanding of the link between the biochemical basis of flower color and the visual perception of the primary pollinators. At the microevolutionary scale, Sánchez-Cabrera et al. identified several anthocyanin biosynthetic pathway loci likely involved in the shift in flower color in the orange/blue polymorphic Lysimachia arvensis. Further, these authors found differential expression of two genes (F3′5′H and DFR) in the anthocyanin biosynthetic pathway. The biochemical analysis of color morphs was consistent with the transcriptome data indicating that the shift from blue to orange petals is caused by a change from primarily malvidin to largely pelargonidin forms of anthocyanins . Authors discuss that both the decreased expression of F3'5'H in orange petals and the differential expression of two distinct copies of DFR, which also exhibit amino acid changes in the color-determining substrate specificity region, strongly correlate with the blue to orange transition. Collectively, these studies have revealed the complexity and nuance of the pigment biochemistry, yet the consistent role of gene expression changes in the anthocyanin biosynthetic pathway underlying the diversity of flower colors.The anthocyanin biosynthetic pathway is mostly regulated at the transcriptional level  that are perceived by pollinators  have petals with UV patterns, whereas others show human-visible patterns or uniform petal color. Koski investigated the evolutionary transition between patterned and non-patterned petals and found that the presence of UV and human-visible patterns evolved independently from one another. He also found that the evolution of human-visible patterns was associated with the evolution of larger flowers, supporting the hypothesis that nectar or pollen guides are more likely to evolve in larger-flowered species. In another study, Roguz et al. explored the evolution of flower color in Iris, a genus displaying a huge diversity of flower color and color patterns among and within species. They found that the most recent common ancestor likely had entomophilous, monochromatic flowers.Phylogenetically controlled studies at the community level have repeatedly found that flower color tends to show weak phylogenetic signal, reflecting an underlying pattern of evolutionary divergence  with a geographical perspective. This study found that the ability of plants that colonized the newly formed environments during Andean orogeny and the ecological changes that followed were concomitant with transitions in flower color as perceived by different pollinator functional groups. Further, this study suggests that habitat and pollination are linked to the history of a plant's lineage.The fate of new color variants depends on a diversity of evolutionary forces. Flower color can affect pollinator attraction and, when investigated in a community context, flower color can mediate different types of interactions among co-flowering species, such as competition, facilitation or mimicry Ghazoul, . The abuTrunschke et al. reviewed studies addressing selection on continuous flower color variation in the context of pollinator interactions. They suggest that evidence for significant pollinator-mediated selection is surprisingly limited among existing studies. In fact, most of the current understanding of flower color evolution arises from variation between discrete color morphs, where selection by pollinators is usually one of the most important factors involved in color variation. Selective foraging by pollinators for specific color morphs is frequently reported  and Medicago sativa . Both studies show significant correlations between flower color and floral display and demonstrate significant directional selection on floral display that indirectly selects for flower color. These examples of correlational selection can partly explain flower color evolution in M. sativa and the maintenance of the flower color polymorphism in S. littorea.Although direct selection on flower color by pollinators has been widely explored, indirect selection on correlated traits is rarely reported , Campanula americana , and Drosera cistifolia . Drought stress is one of the most important factors predicting flower color across geographic ranges . Conversely, other rarely studied, potential abiotic selective agents (such as soil type) do not seem to be related to the geographic pattern of color variation in Drosera cistifolia . The role of abiotic factors on flower color variation has also been reported in this volume. Peach et al. studied the effect of UV radiation on flower color variation in Clarkia unguiculata and found that populations growing in areas of high UV radiation showed higher anthocyanin concentration, a pattern previously reported  and grants from the Spanish government (PID2020-116222GB-I00) and the Andalusian Regional Ministry of Economy, Knowledge, Business and University . MC received scholarships from CAPES Coordination of Superior Level Staff Improvement (grant #88887.583309/2020-00 Finance Code 001) and FAPESP São Paulo Research Foundation (grant #2015/10754-8). Research by MS was funded by the German Federal Ministry of Education (BMBF) grant number 031B0516C and by Alan Dorin and Adrian G. Dyer under the funding scheme from the Australian Research Council Discovery Project 160100161.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.


Gait initiation (GI) challenges the balance control system, especially in the elderly. To date, however, there is no consensus about the age effect on the anticipatory postural adjustments (APAs). There is also a lack of research on APAs in older adults after proprioceptive perturbation in the sagittal plane. This study aimed to compare the ability of young and older participants to generate APAs in response to the vibratory-induced perturbation delivered immediately before GI. Twenty-two young and 22 older adults performed a series of GI trials: (1) without previous vibration; (2) preceded by the vibration of triceps surae muscles; and (3) preceded by the vibration of tibialis anterior muscles. The APAs magnitude, velocity, time-to-peak, and duration were extracted from the center of pressure displacement in the sagittal plane. Young participants significantly modified their APAs during GI, whereas older adults did not markedly change their APAs when the body vertical was shifted neither backward nor forward. Significant age-related declines in APAs were observed also regardless of the altered proprioception.The results show that young adults actively responded to the altered proprioception from lower leg muscles and sensitively scaled APAs according to the actual position of the body verticality. Contrary, older adults were unable to adjust their postural responses indicating that the challenging transition from standing to walking probably requires higher reliance on the visual input. The understanding of age-related differences in APAs may help to design training programs for the elderly specifically targeted to improve balance control in different sensory conditions, particularly during gait initiation. One of the most important requirements of successful locomotion is the ability to adapt gait to the various demands of the environment  to determine to what extent the proprioceptive perturbation of balance affects APAs in young and older adults, and (2) to examine whether such an effect is dependent on age. We hypothesized that altered proprioception from lower leg muscles resulting in a modified representation of the body verticality would significantly affect APAs and this would manifest as a change of the APAs magnitude, velocity, and timing in young adults. In contrast, we further hypothesized that older adults would show decreased ability to appropriately respond to the perturbation due to postural and physiological declines associated with aging.Twenty-two young and 22 older adults  free of Gait was initiated from an upright standing on a custom-made force plate  attached with elastic bands. In the case of triceps surae (TS) muscles, vibrators were fixed to the Achilles tendon of both legs, at the level of the ankle joint, and the vibration-induced body tilt was in the same direction as the forthcoming APAs, i.e., backward. In the case of tibialis anterior (TA) muscles, vibrators were fixed on the tendons of the tibialis anterior, 3–5 cm above the ankle joint, and the vibration-induced body tilt was in the opposite direction as the forthcoming APAs, i.e., forwards. The dimensions and positioning of the vibrators did not disrupt locomotion and they were fixed to the tendons during both vibration and control trials (vibrators off). The activation and deactivation of the vibrators were computer-controlled. The stimulation lasted 5 s with an amplitude of 1 mm and a frequency of 80 Hz. Kinematics of the body  was recorded by the optoelectronic motion capture system  with a sampling frequency of 100 Hz. The vibration-induced body tilt in the sagittal plane was computed from kinematic data as the angle between the shoulder-hip line, i.e., trunk angle (position of the acromion to hip markers) with respect to the vertical : (1) GI without previous vibratory stimulation ; (2) GI preceded by tendon vibration of TS muscles; and (3) GI preceded by tendon vibration of TA muscles. The order of conditions was randomized across the subjects.Participants stood on a force plate in a natural upright posture with their arms alongside the body, feet approximately pelvis-width apart, and gaze fixating on a visual target set at the eye level and located 5 m away from the starting stance position. After the initial 5 s of quiet stance followed either by 5 s of vibratory stimulation  or another 5 s of quiet stance , each participant performed a series of GI trials immediately after hearing an acoustic signal (short “beep”) delivered by the computer. Participants were instructed to step with their dominant leg at a spontaneous velocity and walk straight ahead to the end of the walkway. The acoustic signal was triggered at the same moment as the vibration offset. Participants performed two practice trials to familiarize with the experimental conditions and then five trials were collected in each of the following conditions  was measured by the peak of CoP excursion from the CoP position at the moment of vibration offset which was again arbitrarily assigned a value of zero. Related Time-to-Peak AP, from the onset of APAs to the instant of Peak AP was also measured  was evaluated. The APAs duration (APAd) was measured as the time between the onset and the end of APAs . The level of significance was set at p < 0.05 and effect size  was also computed.Algorithms for CoP signal analysis and evaluation of the variables were written in MATLAB R2020b . The mean of five trials was used for statistical analyses. Repeated measures ANOVAs were used to test the effect of vibration , the effect of age , and their interaction on each variable after having checked normal distribution with the Shapiro-Wilk test. Greenhouse-Geisser adjustments were performed in cases where the assumption of sphericity was violated. post hoc comparisons revealed that in young adults, all APAs variables were significantly different in vibration  compared to control (C) condition , nor TA  muscles and the APAs magnitude. Moreover, young and older participants did not significantly differ neither in backward , nor in forward  vibration-induced body tilt.The partial correlation analysis showed no significant association between the extent of trunk angle induced by vibration of neither TS (Time-to-Peak AP in all experimental conditions compared to young adults (APAd was significantly reduced in the older group only in TS condition. Moreover, a smaller Peak AP and Peak Velo AP were observed in older adults during control GI as well as GI preceded by TA vibration.In addition to different anticipatory postural strategies due to the proprioceptive alteration of balance in young and older adults, further analyses revealed significant age-related declines in the APAs variables regardless of the altered proprioception before GI. The older subjects exhibited a significantly shorter g adults . InteresIn this study, we compared the ability of young and older individuals to generate the appropriate APAs in response to the balance perturbation delivered immediately before gait initiation by bilateral vibratory stimulation of lower leg muscles. In line with our first hypothesis, the young participants significantly modified their postural adjustments during the preparatory phase of stepping and changed all APAs variables under both vibration conditions. In detail, the TS vibration before stepping resulted in backward body tilt to which young adults responded by smaller APAs magnitude and velocity and prolonged APAs duration and time-to-peak compared to unperturbed stepping. On the other hand, when they initiated a step from forward body tilt induced by the TA vibration, they increased the APAs magnitude and velocity while shortening both temporal parameters. As we expected, APAs were modulated according to the internal representation of the body verticality shifted by the vibration of lower leg muscles either forward or backward suggesting that the initial posture strongly influences forthcoming APAs. Our findings agree with previous studies (Rocchi et al., In the current study, we further aimed to investigate the age-related differences in APAs regardless of proprioceptive alteration. During the unperturbed stepping, older adults showed significantly smaller APAs magnitude and shorter Time-to-Peak AP compared to young adults. Congruently, age-related changes in APAs were revealed in previous studies (Henriksson and Hirschfeld, Apart from a significantly reduced APAs magnitude and Time-to-Peak AP due to age in control GI, we found similarly reduced APAs variables also in TA vibration condition. However, in the TS vibration condition, older subjects showed a very similar magnitude of APAs as young adults, but the postural adjustments were significantly shorter and slightly faster than in young adults. We speculate that these different anticipatory adjustments in older adults between the two vibration conditions might be associated with a specific response to the vibration offset (i.e., the moment of vibratory stimulation turn off; Bzdúšková et al., Interestingly, we revealed a significant decrease due to age in parameter APAd only in the TS condition, while Time-to-Peak AP was significantly different between the age groups in all experimental conditions. This indicates that Time-to-Peak would be a more sensitive parameter to detect early APAs impairments as total APAs duration.A strength of the study was the comparison of the ability to generate APAs in response to the proprioceptive perturbation of balance both forward and backward. For the first time, hence, this study uncovered and reported sensitive scaling of APAs in the sagittal plane according to the externally shifted vertical in young adults, and revealed the inability to modify APAs in older adults. Therefore, these results should be taken into account when designing training and rehabilitation programs for the elderly specifically targeted to improve balance control in different sensory conditions, particularly during the transition from standing to walking in order to enhance a more accurate adjusting of APAs and potentially prevent falling. On the other hand, we acknowledge several limitations of the present study. First, we did not collect electromyographic signals from lower leg muscles during the vibratory stimulation and GI which could provide additional information about APAs and would help to interpret age-related differences. Second, we might benefit from the kinematic analysis of the first step performed immediately after the balance perturbation. Further studies should address these limitations as well as investigate whether it is possible to improve the proprioception from lower leg muscles and thus increase the anticipatory responsiveness to perturbation.In summary, aging led to significantly reduced APAs during GI performed from the vibratory shifted vertical as well as from the natural body verticality. Moreover, young adults markedly modulated APAs in response to the vibration delivered before GI, which was in contrast with older adults who showed diminished modulation of APAs. Therefore we can conclude that the ability to generate the appropriate APAs in response to vibratory-induced perturbation particularly in the sagittal plane is age-dependent.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the local Ethics Committee of the Center of Experimental Medicine of the Slovak Academy of Sciences. The patients/participants provided their written informed consent to participate in this study.JK, ZH, and FH contributed to the conception and design of the study. JK organized the database and wrote the first draft of the manuscript. JK and DB performed the statistical analysis. JK, DB, ZH, and FH reviewed the manuscript. All 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.


Clinical supervisors of radiography students play a key role in the facilitation of practice-based learning. However, there is a scarcity of evidence-based strategies to support clinical supervisors. This study aimed at exploring the level of support required by radiographers in order to develop a framework strategy for supporting clinical supervisors of radiography students in Zambia.This study used an exploratory sequential mixedmethods approach. The qualitative phase was conducted first, and the findings were used to develop the questionnaire for the quantitative phase. The study population was radiographers working in the Lusaka and Copperbelt provinces of Zambia. For the first phase, data were collected from a purposive sample of 10 clinical supervisors of radiography students. For the survey, data were collected from 120 radiographers using a questionnaire. In the third phase, a group of experts validated the proposed framework using an online questionnaire. Qualitative data were analysed thematically and quantitative data using statistics.Four support areas were identified: training and education in clinical supervision, clinical training resources, human resources and relationships, and quality assurance programmes related to clinical supervision. These findings informed the development of a support framework strategy for clinical supervisors.This study has revealed that clinical supervision of radiography students requires coordinated support from stakeholders: schools of radiography, professional body, and radiology and hospital management. It is anticipated that the developed framework, when implemented, will enhance the experiences of clinical supervisors and improve the quality of clinical education. Teaching in the clinical environment is an integral part of radiography education which allows students to develop their competence . RadiogrMost of the strategies for supporting clinical supervisors documented in the literature are from the nursing profession: protected time, support groups, and training in supervision –10. HoweIn Zambia, there is a lack of evidence-based strategies for supporting radiographers in the clinical supervision of radiography students. The researcher, being a clinical educator, had also heard radiographers expressing concern about and dissatisfaction with the support received from stakeholders in their roles as clinical supervisors. The aim of this study was to explore the level of support required by radiographers in order to develop a framework strategy for supporting clinical supervisors in Zambia.This study employed a mixed-methods research approach using an exploratory sequential design. Qualitative data were collected and analysed in the first phase and the findings were used towards the development of a questionnaire for the quantitative phase ,15.Study population and sampling: The study population comprises of radiographers working in the Lusaka and Copperbelt provinces of Zambia. The first phase included a purposive sample of ten clinical supervisors working at two teaching hospitals. The criteria for recruitment were radiographers with more than two years' experience in the supervision of students as per the eligibility criteria of a clinical supervisor  Research Ethics Committee. Permission was also obtained from all the heads of the X-ray departments at the study sites. The details of the study were disclosed to each participant and confidentiality and anonymity were assured. In the first phase, informed consent was obtained from each participant, whereas in the second phase, the completion and returning of the questionnaire constituted consent Six participants suggested the establishment of a clinical supervision training programme:Sub-theme 2: Provision of CPD“The Radiological Society of Zambia (RSZ) could offer CPD in clinical supervisi on”. (Participant 9)Three participants suggested the provision of CPD related to clinical supervision:Theme 2: Equipment maintenance and training resourcesThis theme yielded three sub-themes: prompt repair of X-ray equipment, the publication of guidelines and the provision of more consumables during students' placements.Sub-theme 1: Prompt repairs of X-ray equipment“Fix broken imaging equipment on time, so that I can continue with students' training”. (Participant 4)The prompt repairs of X-ray equipment was a support area suggested by three participants:Radiographers attributed the frequent breakdown of X-ray equipment due to a lack of maintenance.Sub-theme 2: Publication of clinical supervision guidelines“The college should provide us with supervision guidelines”. (Participant 1)Five participants suggested the publication of guidelines to guide radiographers in the facilitation of practice-based learning:Sub-theme 3: Provision of adequate Consumables“There is a need to improve the supply of consumables such as X-ray films and contrast media agents because there is a waste of resources during training”. (Participant 2)The provision of adequate resources during students' placement was another support area suggested by four participants:Theme 3: Designated radiographers and incentives for clinical supervisorsThis theme had two sub-themes: appointment of designated radiographers and the provision of incentives for clinical supervisors.Sub-theme 1: Appointment of a designated radiographer in each X-ray department“There is a need to create a link between the schools of radiography and the radiographers involved in supervision by appointing link clinical tutors”. (Participant 10)Three participants suggested the appointment of a dedicated radiographer to act as a link between schools of radiography and placement site:Sub-theme 2: Provision of incentives for clinical supervisors“There is also a need for radiographers who teach students to receive teaching allowances”. (Participant 3)Seven participants suggested some form of material reward for the extra duties' radiographers undertake in clinical supervision:Phase 2: Quantitative approachOut of 160 administered questionnaires, 120 were completed and returned, giving a response rate of 75%. Education and training: The provision of education and training had two suggestions. Equipment maintenance and training resources: Designated radiographers and incentives: Educational audit programme: This study revealed a lack of appropriate knowledge and skills for effective clinical supervision amongst radiographers due to the non-availability of a clinical supervision training programme. Similar findings were identified in studies conducted by Sutton  and Lee A lack of CPD related to clinical supervision came forward from this study. This is an interesting finding because, in a study conducted in South Africa by Mung'omba and Botha , radiogrA lack of communication and coordination between the schools of radiography and clinical training sites came through as a challenge in clinical supervision. For this reason, radiographers suggested the appointment of a designated radiographer to be responsible for clinical supervision. This finding is in line with Walsh  who adviThis study found a lack of incentives as an inhibiting factor to clinical supervision. Radiographers suggested the need for incentives for clinical supervisors in the form of a teaching allowance and education sponsorship opportunities. This finding is in line with a study carried out by Eta et al.  in CamerThis study found a lack of clinical supervision guidelines from the schools of radiography and RSZ. This finding is in contrast with the Society of Radiographers of the UK, which has issued several guidelines to assist radiographers in the facilitation of radiography students' learning ,3,25–27.This study revealed poor maintenance and servicing of imaging equipment. This finding agrees with the Ministry of Health Strategic Plan of 2017 to 2021 , which aRadiographers expressed concerns about a lack of consumables such as X-ray films and contrast media agents. This finding agrees with a study conducted in Rwanda by Ondari et al.  which foThis study revealed a lack of educational audits of clinical training sites. Walsh  states tProposed strategy framework for supporting clinical supervisors: The overarching aim of this study is to develop a framework strategy for supporting clinical supervisors in Zambia. In line with the aim and study findings, the following framework was drafted and proposed  was requested to validate the proposed framework strategy. Data were collected using an online questionnaire in February 2019. The questionnaire was develop based on the seven criteria identified from the literature: clarity, credibility, relevance, efficiency, sustainability, implementability and impact ,33. The The proposed framework is easy to understand”. “The first statement was on the clarity of the proposed strategy framework. The result from The results portray that all validators believed that the proposed framework is clear and simple to understand.The second statement asked expert group members to indicate whether the proposed strategy framework was creditable. “The framework may be developed, but clinical supervisors also need training”. The third statement focused on the relevance of the proposed strategy framework. Data presented in This concern was taken into consideration when developing the framework and included under education and training. The results show that most of the validators were satisfied that the framework was relevant for supporting clinical supervisors.The fourth statement concentrated on the efficiency of the proposed strategy framework. In a fifth statement, expert group members indicated their opinion regarding the implementability of the strategy framework. The sixth statement endeavoured to elicit validators' opinions on the impact of the proposed strategy framework. The results show that four validators “strongly agreed” and two “agreed” to the statement. This finding suggests that all validators were satisfied that the framework could result in positive experiences for clinical supervisors.“There is a need to look at the role of the training institution concerning clinical supervision, e.g. are the training institutions overenrolling and what is the impact of such to clinical supervisors”. The final statement dealt with the sustainability of the proposed strategy framework. This concern was considered during the development of the framework and covered under quality assurance. Evaluation of radiographers in clinical supervision will reveal the impact of over enrolment of students.The comments from validators were not significant enough to make any amendment to the framework. Therefore, the developed framework still maintains the four support areas: training and education, training resources, human resources and relationships, and quality assurance programmes (In conclusion, the developed strategy framework, if implemented, would enhance the experiences of clinical supervisors of radiography students in Zambia. At the time of this study, the researcher was not aware of any framework that guided stakeholders in supporting clinical supervisors of radiography students and this study has accomplished the task of bridging the gap which existed in the literature. Whilst addressing most of the strategies suggested in the framework at the local level, there are others which require intervention at a higher policy level, the Ministry of Health of Zambia. A further study, measuring the impact of the strategies on the experiences of clinical supervisors, following framework implementation, may be undertaken.


Polycystic ovary syndrome (PCOS) is a complex condition, impacting cardio-metabolic and reproductive health, mental health and health-related quality of life. The physical health benefits of exercise for women with PCOS are well-established and exercise is increasingly being recognised as efficacious for improving psychological wellbeing. The aim of this review was to summarise the evidence regarding the effectiveness of exercise interventions on mental health outcomes in women with PCOS.A systematic search of electronic databases was conducted in March of 2020. Trials that evaluated the effect of an exercise intervention on mental health or health-related quality of life outcomes in reproductive aged women with diagnosed PCOS were included. Methodological quality was assessed using the modified Downs and Black checklist. Primary outcomes included symptoms of depression and anxiety, and health-related quality of life.Fifteen articles from 11 trials were identified and deemed eligible for inclusion. Exercise demonstrated positive improvements in health-related quality of life in all of the included studies. Half of included studies also reported significant improvements in depression and anxiety symptoms. There was large variation in methodological quality of included studies and in the interventions utilised.The available evidence indicates that exercise is effective for improving health-related quality of life and PCOS symptom distress. Exercise also shows some efficacy for improving symptoms and/or prevalence of depression and anxiety in women with PCOS. However, due to large heterogeneity of included studies, conclusions could not be made regarding the impact of exercise intervention characteristics. High-quality trials with well reported exercise intervention characteristics and outcomes are required in order to determine effective exercise protocols for women with PCOS and facilitate translation into practice.The online version contains supplementary material available at 10.1186/s12889-021-12280-9. Polycystic Ovary Syndrome (PCOS) is a complex and common condition, affecting 8-13% of reproductive aged women  and althMany chronic illnesses have an impact on mental health and are associated with a reduction in quality of life and an increase in a range of psychological symptoms –11. GiveIn a healthy population, exercise is an effective means of promoting, improving and managing mental health . This isThe current international evidence-based guidelines for the assessment and management of PCOS recommend 150 minutes per week of moderate intensity exercise or 75 minutes per week of vigorous intensity exercise in all women with PCOS, in order to improve general health and quality of life , 25, 26.This systematic review was registered on the International Prospective Register of Systematic Reviews (CRD42019118657) and conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines  andAn electronic database search was initially conducted in December 2018 and updated in October 2021 using Ovid Medline and EBSCOhost , with no date or language restrictions. The search strategy included Medical Subject Heading (MeSH) terms and keywords relating to mental health, health-related quality of life, physical activity or exercise interventions and PCOS. An example of a search strategy is reported in Supplementary Table max or 40 to < 60% VO2max), vigorous (70 to <90% HRmax or 60 to <85% VO2max) or high intensity (≥90% HRmax or ≥85% VO2max) [Included studies involved women of reproductive age (18-45 years of age) and with a diagnosis of PCOS using any established diagnostic criteria . Randomised controlled trials (RCT), non-randomised controlled trials and uncontrolled trials were included. Exercise interventions of two weeks or greater were included in this review (Table  VO2max) .Table 1EThe outcome measures were health-related quality of life as assessed by either the polycystic ovary syndrome questionnaire (PCOSQ) or the short form 36 (SF-36) questionnaire and symptoms of depression and anxiety assessed by any validated questionnaire Table . Trials After duplicates were removed, two reviewers (R.P. and R.B.) independently screened each article by title and abstract. Following removal of irrelevant studies, full-text versions of the remaining publications were assessed for inclusion eligibility. Data relating to study design, participant and intervention characteristics, and outcome measures were extracted independently by reviewers using a pre-determined data extraction form. At each stage of the screening process, discrepancies were resolved by consensus or by a third reviewer (N.S.).. Due to poor reporting of intervention characteristics and outcome measures and large heterogeneity in the interventions, a quantitative synthesis was not feasible. Study results were therefore summarised as statistically significant within group changes (p<0.05).The modified Downs and Black checklist for the assessment of methodological quality was used to evaluate the quality of included studies  Supplem. QuestioThe database searches identified 1114 references. Six articles were removed due to duplication and 1033 articles were deemed irrelevant after title and abstract screening. Of the 76 papers that were deemed eligible for full-text screening, 61 were excluded due to having no relevant outcome measures  , bodily pain, general health perception, vitality, social functioning, role limitations due to emotional problems  and mental health . Four stEight studies measured the effect of an exercise intervention on depression symptoms, with five reporting significant reductions in depression scores. Two studies that reported improvements delivered an aerobic exercise intervention , 40, twoSix studies also examined symptoms of anxiety, three of which reported statistically significant within group reductions in symptoms after an exercise intervention , 38, 40.In summary, exercise interventions reduced symptoms of depression and anxiety in half of the reviewed studies. Due to the large variety of training interventions, conclusions cannot be made regarding the impact of a specific type or intensity of an exercise intervention, compared to another.The current systemic review aimed to determine the effectiveness of exercise on mental health and health-related quality of life outcomes in women with PCOS. Exercise interventions appear to have positive effects on health-related quality of life and associated PCOS symptom distress as assessed by validated measures. The findings for mental health outcomes were less consistent, with a combination of positive and null findings regarding improvements in symptoms of anxiety and depression, although half of the included studies reported improvements in symptoms of anxiety and depression after an exercise intervention. The most common exercise program included various types of aerobic exercise of varying intensities, ranging from moderate to high intensity. Others included some form of resistance training program or a combination of resistance and aerobic exercise. Intervention duration and the inclusion of supervised exercise also varied among interventions. There did not appear to be any common exercise characteristics that could explain differences in symptoms of depression and anxiety, PCOS associated distress, or improvements in health-related quality of life outcomes.This systematic review expands on an existing review of seven trials that found exercise to be beneficial for improving health-related quality of life, depression and anxiety in women with PCOS . Future The current international evidence based guidelines for the assessment and management of PCOS states that psychological factors, including anxiety and depression, should be screened, assessed and managed . It is iGiven that previous research shows that time limitation is reported as the biggest barrier to exercise participation both in a general population and among women with PCOS , the altHalf of the studies included in this review reported significant reductions in anxiety and depression symptoms after an exercise intervention, especially when considering that the reviewed interventions were primarily aimed at improving the physical health, rather than the mental health, of participants. Designing future interventions with a mental health informed rationale for the exercise intervention may improve engagement and therefore result in greater mental health benefits. For example, multi-component interventions that also include additional therapies such as cognitive behavioural therapy could be considered useful and may aid to increase adherence, retention, engagement as well as the maintenance of a healthy lifestyle to improve all health outcomes in women with PCOS . AlthougIn addition, many of the included trials excluded women who were taking medications for the treatment of clinical anxiety and depression. Given the high prevalence of these two mental health conditions in women with PCOS, excluding these women does not adequately represent the population, and therefore, perhaps the true benefits of exercise for these women. We could benefit greatly from future research that examines the effect of exercise in women with PCOS, who display elevated baseline levels of anxiety and depression. Such research would provide greater insight regarding the efficacy of exercise for improving mental health and health-related quality of life in women with PCOS and would increase generalisability and applicability to real-world clinical practice.This review builds on existing knowledge and provides preliminary data to support the inclusion of exercise to manage and improve mental health and health-related quality of life outcomes in women with PCOS. A strength of this review is that it follows the PRISMA guidelines, including double screening of articles, data extraction and quality appraisal of each publication. This review was limited by large variations and poor reporting of exercise characteristics in the included primary studies. This hindered us from being able to conduct a quantitative synthesis of results and limited our ability to form strong conclusions about the effectiveness of exercise, and particular exercise characteristics, on mental health and health-related quality of life in women with PCOS. Future studies should endeavour to adequately report all intervention characteristics, including frequency, intensity, type, format and session duration of exercise interventions and as well as reporting both adherence and compliance to the exercise intervention inform future research.This review found that exercise results in both clinically meaningful and statistically significant improvements in health-related quality of life in women with PCOS. Exercise also appears to have some benefit for improving symptoms of common mental health concerns with half of studies reporting significant improvements in symptoms of depression and anxiety. However, the heterogeneity of included studies, including methodological quality, and the poor reporting of the characteristics of exercise interventions delivered, limited the ability to make conclusions regarding the effectiveness of specific types of exercise. This also limited the ability to conclude the impact of specific exercise characteristics including intensity, frequency and type of exercise for improving mental health in women with PCOS. It is vital to employ strategies that can both reduce symptoms of anxiety and depression and increase adherence to interventions. Therefore, multi-component interventions that integrate psychological treatment with exercise and address the complex physical and mental health concerns of women with PCOS have the potential for improving mental health outcomes. Future studies should aim to address barriers to exercise participation and determine which intervention characteristics are associated with increased engagement and maintenance of exercise for the promotion of mental health in women with PCOS.Additional file 1.Additional file 2.Additional file 3.


Injuries to the knee ligaments can be particularly disabling in young patients, given the risk of long-term disability if adequate fixation is not achieved during initial repair. The TWINFIX™ titanium (Ti) suture anchor with ULTRABRAID™ Suture  was designed to secure tendon and ligament reconstructions with increased boney ingrowth at the anchor site with minimal invasive technique. This retrospective analysis looked at 33 patients (41 implants) operated with this device between 2015 and 2019 at a single institution. The average age of patients was 33.18 years , with an average body mass index of 24.88 . The indications were lateral extra-articular tenodesis during anterior cruciate ligament reconstruction, medial patellofemoral ligament reconstruction, quadriceps or patellar tendon repair and medial collateral ligament repair. After an average follow up of 24.3 + 6.53 months, there was no reports of clinical failure or radiographic evidence of implant failure or loosening. One patient experienced a complication unrelated to the study device, requiring manipulation under anesthesia with resolution of symptoms. This case series supports the safety and performance of this implants for the knee procedures in which its use is indicated. Additional follow-up will be required to determine whether these effects are sustained at medium- and long-term durations. Although suture anchors are an established therapeutic option within orthopaedic  and sporThere are numerous indications for suture anchors in knee ligament repair procedures , includiEmerging trends for anterior cruciate ligament (ACL) reconstruction involves adding a lateral extra-articular tenodesis (LET) or anterolateral ligament reconstruction  since thThe TWINFIX™ titanium (Ti) suturanchor with ULTRABRAID™ Suture  was designed to offer additional strength and stability over traditional suture systems.While there have been studies evaluating the advantages and disadvantages of various fixation methods for Knee Ligament Reconstruction ,18, no cWe hypothesized that the use of these anchors or fixation’s methods are the ideal treatment method or at least one more therapeutic option for providing stable fixation and satisfactory clinical outcomes after a 6-months minimal follow-up. The purpose of the study was (1) to describe arthroscopic anchor suture-bridge fixation as a novel technique for treating tibial intercondylar eminence fractures in adults; and (2) to analyze the minimal follow-up results of the radiographic and clinical outcomes.From July 2015 (after introduction of the device) to December 2019, 33 consecutive patients underwent knee ligament repair procedures with the study device at a single hospital center. Patients who met clinical criteria for operative intervention had the following injuries and indications: ACL reconstruction with anterolateral reconstruction, extra-capsular MPFL reconstruction, quadriceps or patellar tendon repair, and medial collateral ligament (MCL) repair. All included patients were evaluated by a sports medicine fellowship trained orthopaedic surgeon and operated on by the same hospital team.The average age of patients was 33.18 years , with 10 under the age of 21. Patients had an average body mass index of 24.88  and were followed for an average of 24.3 months  postoperatively.The study protocol was in accordance with standard ethical and human research principles. Written informed consent for participation and publication was given by a parent of each participant, including the publication of photographs. The study was approved by the Research Ethics Committee of the Principado of Asturias , Spain.All patients received same devices of Titanium, preloaded with the ultrabraid suture for soft tissue attachment in the bone and had signs of knee joint instability (between femur and tibia or between femur and patella) or functional insufficiency on quadriceps or patellar tendons prior to the procedure. Once the implant was placed inside the bone, there are two possibilities or direct fixations by means of a loop with the knot on the ligament itself or by means of a suture to the ligament according to the Krackow technique  in orderThe primary outcome was implant failure, which was defined as any implant with one of the following three conditions: clinical instability used the Knee Injury and Osteoarthritis Outcome Score (KOOS). The KOOS comprises 42 items in 5 separately scored subscales assessing pain and function of the knee in patient with injury or osteoarthritis .The subscales are divided in Pain (nine items); Symptoms (seven items); Function in daily living (ADL) (17 items); Sport and Recreation Function (Sport/Rec) (five items); Quality of Life (QoL) four items. Each item is rated on a 0- to 4-Likert scale, and each of the five subscales is calculated as the sum of the items included. Scores are then transformed to a 0–100 scale. The measure generates five separate scores where the higher the score, the best the health state.The presence or absence of local inflammatory signs, stiffness or pain, as well as general patient variables such as age, sex and body mass index, were recorded as secondary variables. The participant was asked to return after 6 months and then score the KOOS he or she had perceived during the previous 3 days.® . The Shapiro–Wilk test applied to the data showed the distribution to be normal in the pre and postoperative evaluation. It was therefore decided to use Student’s t-test for paired samples to compare Pre-Post and the effect size by Cohen’s d. Differences were considered to be statistically significant if p < 0.05.Data were analyzed with the IBM SPSS 24Thirty-three patients (41 implants) underwent operative intervention with procedures that required the implantation of a suture anchor. Of the 33 patients, 27 had one implant (27 implants), five had two implants (10 implants), and one had four implants .Indications for surgery included 24 patients with LET during Anterior Cruciate Ligament (ACL) reconstruction , two patients with extra-capsular MPFL reconstruction , three patients with quadriceps or patellar tendon repair (inside of the respective bone), and four with MCL repair  .All 33 patients had postoperative radiographs, which demonstrated visible implant tracks in the knee. There was no evidence on initial or repeat imaging, or upon clinical examination, of implant failure, dislocation, or loosening in any patient.p < 0.001).The mean preoperative and of post- operative KOOS score are shown in There were three reported non-serious adverse events after ACL reconstruction: two cases of minor dysesthesia in the knee and one case of femoropatellar pain. One patient had to return to the hospital for two days because of fever, stiffness, and swelling one week after surgery was performed. No infection was diagnosed, and the patient’s symptoms resolved with medication only.Only one patient had complications that required return to the operating room. The patient had a post-operative local infection, swelling, and stiffness, which required manipulation under anesthesia. He subsequently developed lateral inflammation above the anterolateral ridge and required antibiotics, cleaning of the wound, and small drainage by means of one minimum incision. This resulted in resolution of symptoms.None of the complications mentioned above were considered to be related to the study device.The most important finding of this study was to know the possibility for using these types of metallic implant in knee surgery for ligaments or tendons reconstructions, and the no presence of adverse effects. These Suture Anchors are designed to provide secure reattachment of soft tissue to bone and facilitate bone ingrowth. Attachment of soft tissue is performed with the surgeon’s preferred technique. These devices can be used with instruments such as drills, threaded dilators, and awls.The body of these anchor products is fabricated from ASTM F-136 titanium alloy. Both anchors come preloaded with a non-absorbable suture. All sutures are made of ultra-high molecular weight (UHMW) polyethylene fiber. In terms of mechanical design, the primary difference between the two anchors relate to eyelet placement. The Ultra Ti suture anchor contains a distal suture eyelet that accommodates internal suture routing, enabling anchor cortical fixation. The Ti suture anchor contains a proximal suture eyelet that does not afford anchor thread engagement with the cortical layer .Approximately 97% of extra-capsular repair cases with LET combined with ACL reconstruction relied on implants placed on the lateral tibial surface at a location point situated halfway between the fibular head and the Gerdy´s tubercle by means of a minimally invasive incision .There was no complication related to the use of this implant in the knee joint procedures. Occurrence of patient complications such as joint rigidity (slow return of range of motion) was entirely related to healing of the surgical joint incision and not related to the implant. Because of the lateral extra-articular approach used for implants, only a distal minimal incision (described above) is needed, which has the clinical benefit of foregoing much higher disruption and morbidity associated with transosseous fixation.This technique also has the advantage that it can be used in pediatric patients, with the anchor implant placement achieved by radiographic control with a minimal incision and placing the anchor in the correct epiphyseal location to avoid injury of the cartilage growth zone and preserve the integrity of the bone growth plate . All patIn the future, the possible development of non-metallic implants may help to avoid magnetic resonance imaging interference and more closely match the mechanical and biological properties of bone. The current anchor product allows for achieving accurate and safe repair, with fixation of the knee tendons on bone (in this situation combining different repair techniques) in a similar fashion to other joints such as the shoulder .This is As previously described, the LET supports greater improvement for the rotational stability of the knee in the context of ACL reconstruction, and should result in a greater survival of the graft  ,21. ThesIn our practice, we prefer the use of this type of implant to using a linear strip of the iliotibial band, which could weaken the lateral area of the knee, especially if the Kaplan fibers are damaged.The limitations of this technique were the possibility of presence of more implications in the evaluation’s methods, as for the ligament injury, the affected range of mobility because of the affected tendons or the presence of osteoarthritis previously to the surgery.In conclusion, this retrospective case series supports the safety and performance of these implants for the knee procedures in which its use is indicated used the KOOS outcome measure. Additional follow-up will be required to determine whether these effects are sustained at medium- and long-term durations.


Introduction: The middle turbinate (MT) is the most important anatomical structure inside the nasal cavity and a landmark in the identification of skull base, ethmoid cells, and lamina papyracea. Postoperatively, lateralizationof the MT can cause synechia and obstruction of the middle meatus and the maxillary, ethmoid, or frontal sinuses.Objective: To review the current literature about the outcome of different techniques used intraoperatively to prevent lateralization of MT after functional endoscopic sinus surgery (FESS).Materials and methods: This retrospective narrative literature review provides a summary of current and past research publications about different techniques used intraoperatively to prevent MT lateralization after FESS.Results: Many methods have been described to prevent the lateralization of MT and synechiae formation. These methods include controlled synechiae, suture lateralization, metal clips, partial resection of MT, middle meatus implants, and steroid-eluting implants and stents.Conclusion: The ideal FESS should include preservation of the MT, reducing its lateralization, and preventing synechia formation.Different techniques have been discovered in an attempt to prevent this complication. The middle turbinate (MT) is an anatomical structure inside the nasal cavity that plays an important function in nasal air flow and olfaction . It is cMethods and materialsThis retrospective narrative review covers literature from the period 1992-2019. An electronic search was done using PubMed, Medline, and Ovid Science Direct databases using the keywords “synechia, Middle Turbinates, Sinus surgery”. The search unearthed a large volume of diverse materials that have been used to prevent lateralization of MT after FESS. We included papers and texts published in English that met the objectives of the review.Inclusion criteriaPatients who underwent FESS with varying intraoperative techniques to prevent the lateralization of the MT.Exclusion criteriaPatients who underwent FESS without any known technique to prevent the lateralization of the MT.Results and discussionAnatomic Characteristics of MTIt is important to review the MT anatomy to understand the dynamics of MT lateralization. It has four different parts, an anterior buttress, a posterior buttress, a vertical attachment, and a horizontal attachment. The anterior buttress is a point of attachment of the MT to the lateral nasal wall below the agger nasi. The posterior buttress is a point of attachment to the lateral nasal wall near the posterior end of the MT. The vertical lamella attaches superiorly to the lateral cribriform plate lamella, providing stability for the anterior MT and makes the boundary between the cribriform plate and the ethmoid roof. The horizontal lamella  is attached laterally to the lamina papyracea and extends downwards to the posterior buttress .Incidence of MT Lateralization After FESSSynechia formation between the MT and the lateral nasal wall is the most common surgical complication of FESS, which occurs in 43% of patients . Other sCauses of MT LateralizationOne of the first steps of FESS is the medialization of MT to provide proper exposure of the OMC components. The MT might be destabilized after medialization, which can lead to its lateralization and formation of synechia when the raw mucosal surfaces are left in apposition -16. MT lThe Debate of MTMT is a key structure in FESS but the adequacy of its management remains controversial . Some auTechniques to Prevent MT Lateralization After FESSMany techniques have been designed to prevent synechiae formation -20. Each1- Controlled synechiae (Bolgerization): This was developed by Bolger et al. in 1999, and has been found to be effective in the prevention of MT lateralization in 88% of patients . It invo2- Conchopexy technique: The needle is introduced into the left nasal cavity and passed through the head of the MT, septum and the contralateral MT in a single pass then brought back to the right MT and passed through the septum to the initial side to be knotted with left MT.Many authors reported endoscopic conchopexy technique as the most effective method to prevent MT lateralization with high success rate (90%-92%) . It cons3- MT Medialization with metallic clips: Medialization of MT using metallic clips is an effective method of preventing MT lateralization with success rates reaching up to 96% . It cons4- Partial resection of MT: The resection of the lower third of the MT that corresponds to the ethmoidal infundibulum by utilization of curved cutting scissors, or shaver is another method . Partial5- Middle meatus implants (silastic stent): Middle meatus implant is a technique proposed to place a proper size of inverted U-shape polymeric silastic sheet according to the size of the nasal cavity, the size of the MT, and the height and depth of the middle meatus. It is inserted between the middle meatus and caudal portion of the nasal septum and fixed it with mattress suture. The silastic sheet can be removed 10 to 14 days after FESS -30. The Another technique described by Jebeles and Hicks is the application of a 1 cm × 1 cm Merocel pack  between the bulla ethmoidalis and MT, this pack is placed for two days to stabilize the MT . However6- Steroid-eluting implants and stents: Bioabsorbable steroid-eluting sinus stents are inserted into the sinuses to maintain sinus patency, stabilize the MT, reduce synechia formation, reduce the need for systemic anti-inflammation medication, reduce medical and surgical interventions and improve outcomes. The slow release of steroids for a period of 30 days aims to reduce inflammation and edema of sinuses mucosa and improve wound healing -35. CurrThe MT is an important surgical landmark during FESS. Many methods have been proposed in the literature as useful, effective measures for preventing MT lateralization and synechia formation after surgery. Most of those methods achieved a favorable success rate in preventing unstable, floppy MT with few difficulties and complications.


Perinatal mortality includes both fetal demises (stillbirths) and deaths in the first week of life. Worldwide, there are over 6.3 million perinatal deaths a year, almost all of which occur in developing countries . StillbiThe primary rationale for this Research Topic has been to advance the state of knowledge and expertise for investigating the neuropathology of unexplained perinatal deaths and, in particular:contribute to the identification of the pathogenic mechanisms underlying these deaths , in the context of interactions with environmental risk factors  and neuropathological findings.facilitate the development of evidence-based prevention and management strategies to decrease the incidence of these inexplicable and devastating deaths.Another aim of this proposal was to deepen knowledge regarding developmental brain dysfunctions that can manifest later in life as neuropsychiatric symptoms, impaired motor function, learning, language, or non-verbal communication behaviors such as crying, or autism spectrum disorders –12. A reThis Research Topic presents a series of articles and reviews written by leading authors and covering most aspects of state-of-the-art research on the neuropathology of fetal and infant sudden death and other neurodevelopmental disorders.The papers are grouped into two main sections, according to the purposes of the Research Topic:1) Neuropathology of Sudden Unexplained Perinatal Death2) Neuropathology of Other Neurodevelopmental Disorders1) Neuropathology of Sudden Unexplained Perinatal DeathThe articles are distributed in the following sub-sections:(a) Neuropathological research on sudden infant deathBlackburn et al. present an epidemiological study on the neuropathology of sudden infant death syndrome (SIDS). These authors point out that the underlying death mechanism reported in many studies is highly controversial. Using machine learning tools, they emphasize the existence of three distinct groups of SIDS, each with a unique peak age of death, and specific epidemiological and extrinsic risk factors.McGuone et al. provide a review on Sudden Unexplained Death in Childhood (SUDC), i.e., the unexpected death of a child over 12 months of age that remains unexplained after a thorough case investigation. The authors emphasize the scarce and unsatisfactory nature of literature on this subject, especially on the neuropathology of SUDC, and advocate greater interdisciplinary participation in research efforts to elucidate the underlying mechanisms, especially to institute preventive strategies.(b) Neuropathology of neonatal breathingHarper and Kesavan. This interesting article reviews, among other topics, the rationale and empirical evidence for use of peripheral locomotor muscle pacing as an alternative intervention for disordered breathing, an often overlooked mechanism to stabilize breathing.A thorough description of the multiple systems and mechanisms that underlie regulation of breathing and cardiovascular processes in newborns is represented by the contribution of (c) GeneticsPHOX2B gene  and sudden unexpected infant death (SUID/SIDS). The authors report, for the first time, on the genetic screening of the three exons of the PHOX2B gene in Italian IALTE and SUID/SIDS cases. The study finds a statistically significant association between common 3′UTR variants in the exon 3 of the PHOX2B gene with these two pathologies, suggesting that CCHS, ALTE, and SUID/SIDS might be members of the same group of respiratory autonomic disorders of infancy.Congenital central hypoventilation syndrome (CCHS) is a genetic neurodevelopmental disorder with an autosomal dominant transmission caused by heterozygous mutations in the X2B gene . BachettKe and Chen report a rare case of a heterozygous nonsense mutation in the CTNNB1 gene in a 15-month-old girl with a complex phenotype  associated with a neurodevelopmental disorder with spastic diplegia and visual defects.(d) Immunohistochemical studiesAlwazzan, Mehboob, Hassan et al. analyze the immunoexpression of Neurokinin-1 receptor (NK-1R), a receptor of tachykinin peptide substance P (SP), in miscarriage occurring in the first trimester of pregnancy. The authors highlight the involvement of SP/NK-1 receptor system dysregulations in these deaths and suggest the use of NK-1R antagonists to diagnose and treat spontaneous abortion.Alwazzan, Mehboob, Gilani et al. shows that the alpha 7-nicotinic acetylcholine receptors (α7-nAChR) are highly expressed in the placenta and products of conception during the first trimester. These receptors could then be involved in sudden fetal deaths and complications of pregnancy.Another immunohistochemical study by (e) Perinatal environment exposureBednarczuk et al. The authors examine literature in this field, emphasizing the mechanisms by which smoking in pregnancy can cause brain abnormalities in sudden intrauterine unexplained death syndrome (SIUDS) and SIDS and the need to educate women on these harms.The harmful effects of maternal tobacco smoke on the nervous system of fetuses and newborns are covered in the mini-review by Lucchini et al. investigate the effects of chronic tobacco and alcohol consumption during pregnancy on autonomic function in a wide population of fetuses at ≥34 weeks gestational age, by quantifying heart rate, heart rate variability, movement, and heart rate-movement coupling. The results of this study contribute to identifying new biomarkers and understanding the mechanisms underlying risk for adverse outcomes.Vivekanandarajah et al. Through a multicenter longitudinal study and by using autoradiographic methods to highlight the nicotinic receptor binding in the brainstems of infants dying of SIDS, the authors provide evidence that developmental factors paired with changes in nicotinic receptor binding are related to the cause of death as well as exposure to maternal cigarette smoking.The serious consequences of cigarette smoke and alcohol absorption in pregnancy are also the focus of the contribution by 2) Neuropathology of Other Neurodevelopmental DisordersWard et al. compare hypoxic ventilatory responses in mice with cell-type specific knockout or rescue of Mecp2. The study suggests that MeCP2 expression in excitatory, inhibitory, or dopaminergic/noradrenergic neural cells is essential for normal hypoxic ventilatory responses. The authors explore the implications of these findings for the pharmacological treatment of breathing abnormalities and understanding the pathophysiology of sudden death in Rett syndrome.Rett syndrome is caused by the loss of function of the transcription factor methyl CpG-binding protein 2 (MeCP2) . In an eSingh et al. This study, which focuses on the autonomic features of sudden unexpected death in pediatric epilepsy, offers interesting indications on the management of epilepsy in patients with Rett Syndrome.Another interesting contribution on the Rett Syndrome is given by the systematic review article of Di Lascio et al. The study analyses various in vivo and in vitro approaches aimed at better understanding the CCHS molecular pathogenetic mechanism, in order to reduce the damage caused by the aberrant function of mutant PHOX2B and provide new therapeutic strategies.Congenital central hypoventilation syndrome (CCHS) is the focus of the review article by Gotchac et al. The authors develop a new rodent model, using acute hypoxic cardiac arrest to induce HIE-like injury in post-natal rats. The study, which combines radiological, histological, and behavioral testing, finds that neurological changes that persist into adulthood, suggesting that the model may recapitulate milder forms of HIE. This model may be useful for understanding the long-term neurological and psychiatric consequences of oxygen deprivation during perinatal life.New insights into hypoxic ischemic encephalopathy (HIE) of the full-term newborn derive from the experimental study by Together, these publications expand current knowledge on the neuropathology of sudden unexplained perinatal/infant death and other neurodevelopmental disorders, such as the Rett syndrome and CCHS, thus allowing the broadening of the diagnostic criteria and preventive strategies. As editors of this Research Topic, we express our sincere gratitude to the authors who accepted the invitation to participate and for their significant efforts in identifying interesting approaches that explain the pathogenesis of these conditions. We would also like to thank the reviewers for their significant comments, elevating the quality of the submitted articles. Finally, we thank Frontiers and, in particular, the editorial office for essential support.AL, AA, and WF: the editors of this Research Topic, together wrote the editorial that summarizes the contents of all the 13 published articles. All authors contributed to the article and approved the submitted version.AA was funded by the International Rett Syndrome Foundation (#3803).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.


The interplay between infections and rheumatic diseases has been a constantly evolving field for several reasons. First, a number of infections often manifest with primarily immunologic phenomena, as for example happens in hepatitis C virus-related cryoglobulinemic vasculitis or parvovirus or Chikungunya-associated arthritis. Second and more importantly, infections have been and continue to be among the most serious comorbidities in rheumatic patients treated with immunosuppressive or immune-modulating therapies. The latter issue has become more prominent in the last 20 years after the introduction of biologic and targeted synthetic therapies in daily clinical practice.“Infection-Related Rheumatic Diseases,” hoping that it will provide a better understanding of this complex interaction between infection and rheumatic disorders.We present here a Research Topic collection of four articles entitled Calabrese et al. present their perspective on the contemporary landscape of infections after the launching of targeted (biologic and synthetic) therapies. They not only focus on infections associated with specific agents that were expected by preclinical research [i.e. tuberculosis and Tumor Necrosis Factor (TNF)-inhibitors], but also in severe infectious entities like progressive multifocal encephalopathy (PML) after natalizumab or rituximab that, although rare, need increased vigilance for their prevention and early detection. They also emphasize the significance of big data and post-approval surveillance for the documentation of potential links between novel therapies and specific infections. The authors finally suggest measures for early recognition of patients at risk for severe infectious complications, such as the use of prediction scores  in South Korea. The issue of tuberculosis reactivation in patients treated with biologics, especially TNF-inhibitors, has been widely studied during the last 20 years and numerous scientific organizations have provided detailed guidelines for the effective screening and treatment of latent tuberculosis in rheumatic patients before biologic treatment initiation. However, the risk in patients with SNV treated mostly with conventional synthetic DMARDs and immunosuppressives has not been studied extensively. The authors reached to some interesting conclusions. First, they find a 6-time higher TB incidence in SNV compared to general population, both in men and women. Second, with the exception of eosinophinic granulomatosis with polyangiitis (EGPA), the finding was almost constant for other types of SNV. Third, the risk ratio was significantly higher during the first 3 months after diagnosis that aligns with the induction of remission regimens and the high glucocorticoid doses at the initiation of treatment in SNV. Despite some noteworthy limitations , this is a valuable study for the better understanding of TB in this vulnerable population.In the second article by Abdallah and Abu-Madi, the authors focus on the genetic background of rheumatic heart disease (RHD). Although rare in Western countries, the topic still is of great interest for a variety of reasons. The first is that the death toll in low- and middle-income countries still is worrisomely high , a synthetic double stranded RNA mimicking viral infection, in an animal model of SS (SS-like NOD/ShiLtJ mouse). They found that poly(I:C) administration enhanced the inflammatory lesions in salivary glands, most likely through the action of interferon-induced signals and interleukin-33, a cytokine involved in Th1 signaling.Finally, there has been a speculation over long time about the potential involvement of viral infections in the pathogenesis of Sjogren's syndrome (SS). In this article collection, In conclusion, these articles show on the one hand how infections can participate in autoimmune processes and on the other hand, the potential of various immune-suppressive/modulating treatments used for the treatment of rheumatic diseases to increase the risk for common or opportunistic infections.KT and CC conducted the manuscript. DV made the final amendments and approved the final version. All 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.


The melanin fluorescence emitted by pigment cells of the human skin has been a central research topic for decades, because melanin, on the one hand, protects against (solar) radiation in the near-UV range, whereas on the other hand, melanocytes are the starting point for the malignant transformation into melanoma. Until recently, however, melanin fluorescence was not accessible in the context of conventional spectroscopy, because it is ultraweak and is overshadowed by the more intense so-called autofluorescence of endogenous fluorophores. The advent of a new method of laser spectroscopy has made this melanin fluorescence measurable in vivo. A stepwise two-photon absorption with 800 nm photons is used, which more selectively excites melanin (dermatofluoroscopy). Our review summarizes the experimental results on melanin fluorescence of the four types of cutaneous pigment cells from healthy and malignant tissues. Outstanding is the finding that different types of melanocytes  show characteristically different fluorescence spectra. The possibilities of using this melanin fluorescence for melanoma diagnosis are shown. Moreover, the uniform fluorescence spectra emitted by different melanoma subtypes are essential. Conclusions are drawn about the molecular processes in the melanosomes that determine fluorescence. Finally, experimental suggestions for further investigations are given. As a skin pigment, melanin may be viewed as a double-edged sword: on the one side, melanin acts as a parasol protecting epidermal stem cells from UV-induced DNA damage, and on the other side, the melanocytes that produce melanin carry the risk of transformation into melanoma, one of the most aggressive and deadliest forms of skin cancer. Melanin exerts its protective effect on the normal pigment cells, which are termed “melanocytes.” On the way from aggregated pigment cells (nevomelanocytes) of benign/common nevi or nevomelanocytes of dysplastic nevi towards melanoma cells, the effect of melanin shifts away from its original benefits to malignancy .The objective characterization of these four subtypes of melanocytes with spectroscopic methods has been the goal of extensive research for decades, because a clear-cut differentiation either in vivo (directly on patient skin) or ex vivo  could be of great benefit for the diagnosis of melanoma.In the past, much attention was paid to the fluorescence of melanin with the most crucial question to be answered: Is it possible to specifically measure melanin fluorescence in the skin and is it possible to differentiate the four subtypes of melanocytes in this way?With regard to melanoma cells, the question was expanded, because “melanoma” presents itself in a variety of subtypes, which differ according to growth patterns, anatomical localization, and patterns of genetic aberrations ,3. MelanA breakthrough in terms of the measurability of melanin fluorescence in tissue came with a special technique of non-linear spectroscopy, the stepwise two-photon excitation of fluorescence ,10,11,12Differentiation/characterization of the four types of pigmented skin cellsDetectability of all melanoma subtypesWith dermatofluoroscopy, the ultraweak melanin fluorescence can be measured without interference from background autofluorescence. It turns out to be a meaningful source of information on the issues addressed above:On this basis, a new and objective melanoma diagnosis is possible both in vivo directly on the patient skin ,18,19,20The results of the most important studies investigating dermatofluoroscopy are summarized below. In addition, we demonstrate that measuring the melanin fluorescence is an informative predictor for molecular processes in the melanin microenvironment in the melanosomes and their changes in the process of malignant transformation into melanoma cells. Finally, suggestions for further investigations on current issues of melanin spectroscopy using nonlinear spectroscopy are given.In conventional spectroscopy, melanin is transferred from the ground state to the fluorescent excited state by absorption of one (UV) photon a. Howevestepwise excitation by two photons of lower energy (800 nm). Melanin is first brought into an intermediate state and from there into the fluorescent excited state  In vivo on pigmented lesions of the skin, (ii) ex vivo on surgically removed specimen of suspicious lesions, and (iii) on the corresponding histological FFPE preparations . The entire database of measurements consists of several tens of thousands of spectra.The examined individuals were of the Caucasian skin type (Fitzpatrick skin types 1–4). Most individuals of the database were patients of a dermatological practice in Berlin, or the dermatological clinic of the St. Josefs Hospital of the Ruhr University, Bochum. Freshly excised specimen and FFPE preparations originated from patients of the Dermatology Clinic at Vivantes Klinikum Berlin-Südost. In all cases, written informed consent of patients was obtained.between these four types of spectra, but within each mentioned cell type the spectra are largely identical.The most important result of the investigations into several hundreds of samples of pigmented skin tissue, i.e., tens of thousands of measuring areas, is that there are only four types of fluorescence spectra. These spectra belong to the four different pigment cell types: melanocytes, nevomelanocytes, dysplastic pigment cells, and melanoma cells ,13,17,20In The fluorescence spectrum of melanin in melanoma cells is given in This uniform spectral fluorescence shape of melanoma-derived melanin is mathematically characterized in that the first derivative of the intensity course I(lambda) over the wavelength lambda, dI(lambda)/d(lambda), the gradient, is a straight line over the entire range of 430–650 nm.The uniform fluorescence spectrum of melanin in atypical pigment cells  is shown in With an automated evaluation of measured fluorescence spectra, with a fixed root mean square error (RMSE), an automatic assignment to one of the four types of spectra is possible ,17,19,25The ex vivo fluorescence spectra of melanin in the four pigment cell types * correspond to the in vivo spectra  of the fluorescence excitation radiation. This means: Whereas in the intact dermis the second harmonic of the excitation radiation (400 nm) is generated in the microcrystalline structures of collagen, the tumorous destruction of the dermis leads to disruption of the microcrystalline structure and thus to failure of the SHG ,25.It is worth mentioning that the uniform melanin fluorescence spectrum of melanoma d  can give rise to fluorescence interfering with the measurements and should be avoided. Nevertheless, spectra of such artifacts are recognized in the automatic evaluation of the fluorescence data and the corresponding tissue sample is removed from a diagnostic evaluation.Early detection of all melanoma subtypes, and for both, de novo melanomas as well as those developed on a pre-existing nevus.Perspective of non-invasive follow-up of suspicious pigmented lesions.Characterization of the malignant potential of eruptive nevi .Presurgical definition of incision line for complete excision of melanoma lesions.Optimal tailoring of paraffin-embedded specimen for the preparation of histopathological slides, especially in lesions with eccentric positioning of the most suspicious region.Objective assistance or second option for the dermatohistopathologist to arrive at a final histopathologic diagnosis (the present gold standard of melanoma diagnostics) for all melanoma subtypes except LM/LMM. Dermatofluoroscopy may particularly support dermatopathologists in the diagnosis of melanocytic lesions with uncertain malignant potential, e.g., MELTUMP or STUMP; atypical congenital nevi of childhood; or in cases of trans-epidermal melanocytic migration . Based Fluorescence spectra as shown in absorption spectra of the four cell types are largely identical: they show a monotonously decreasing curve over the entire visible spectral range towards the red.** Thus, the fluorescence in the process of malignant melanocytic transformation shows an increasing red shift compared to the absorption . What conclusions can be drawn from this observation about molecular processes?Dermatofluoroscopy reveals pronounced spectral changes in the melanin fluorescence of the four types of pigment cells, particularly when ranking these according to the process of malignant transformation see : from a 6 of such melanin oligomers form what is known as granules. These melanin granules are attached to a fibrillar matrix, localized in melanosomes bound to the lipid membrane. The melanin oligomers provide the pi-electron system, which determines the spectroscopic properties considered here.The melanin fluorescence of cutaneous pigment cells has its origin in melanin oligomers. These oligomers are the fluorescent units. They consist of 3–6 sub-units , which aIn ordinary organic molecules with pi-electron systems, the cause of a redshift of fluorescence compared to absorption is a vibrational relaxation in the final state of the electron transition, the so-called Franck–Condon (FC) state. This relaxation is triggered by the fact that in the FC state the core configuration corresponds still to that in the ground state, but the electron density distribution is already changed. This vibrational relaxation leads to an energetic lowering of this excited state. The fluorescence resulting from this relaxation is red-shifted compared to the absorption.2O at 510 nm, in DMSO at 575 nm [For molecules in solution, additional energetic lowering of the fluorescing excited state is possible due to a changed interaction with the solvation shell. This so-called solvatochromism can lead to large Stokes shifts of up to several hundreds of nanometers. This phenomenon can also be observed with dissolved melanin, and with a different shift with different solvents, e.g., fluorescence maximum in HIn the case of coupled oligomers as the origin of the melanin fluorescence in pigment cells, instead of the solvation shell there is the complex microenvironment (protein matrix) of the melanosomes . A red s(i) a minimization/elimination of the interaction of the melanosomes with the keratinocytes via the dendrites in the sequence from melanocytes via normal and atypical nevomelanocytes to melanoma cells  and/or.(ii) a gradual dissolution of the melanosome membrane in in the process of melanomagenesis ,34.At present there are not enough experimental results to specify the various mechanisms, but the following findings can be helpful: (i) The robustness of the fluorescence spectra with respect to the dehydration in the process of the histological preparation of tissue specimen (see above), (ii) the even further red shift of the fluorescence in skin types 5 and 6 .** This melanin absorption represents a remarkable exception to the usual structured band spectra of organic molecules and pi-electron aggregates. According to current knowledge, this monotonous melanin absorption in the visible and near-infrared spectral range is the envelope of sub-bands . This isWith the method of dermatofluoroscopy (stepwise two-photon excitation), the ultra-weak melanin fluorescence of pigmented skin tissue can be measured selectively and spectrally resolved in the visible spectral range. It shows that (i) the melanocytes of normally pigmented skin, the nevomelanocytes of benign and atypical (dysplastic) nevi and the melanoma cells each show a distinct spectral pattern of fluorescence, and (ii) the melanin spectrum of the melanoma cells is independent of the melanoma subtype.This novel method of dermatofluoroscopy is well suited to diagnose melanoma. It can be used both on patient skin (in vivo) and on freshly excised or formalin-fixated and paraffin-embedded surgical specimen (ex vivo). The four characteristic melanin fluorescence spectra are measures of the molecular structures of the fluorescent pi-electronic melanin units and their relaxation processes. These are influenced—in characteristically different ways—in the four types of pigment cells by the microenvironment in the melanosomes. For further basic research on the molecular processes of malignant melanocytic transformation, it is recommended to use the following methods of nonlinear spectroscopy on each of the four different pigment cell types: (i) Investigation of stepwise as well as simultaneous two-photon fluorescence excitation spectra of melanin with variable excitation wavelength in the red/near infrared region, (ii) hole-burning absorption spectroscopy , preferaSuch investigations could elucidate fluorescence-relevant differences in the subband structures of the melanin absorption spectra. The following examinations using dermatofluoroscopy could contribute to the further qualification of this method for melanoma diagnosis: (i) Inclusion of less frequent melanoma subtypes, e.g., mucosal melanoma , (ii) coA transfer of available research results concerning melanin fluorescence is currently under way to further elucidate its role in Parkinson’s disease as well as in human tissue containing neuromelanin . Other p


Pain is the most common cause of disability in IBD. What causes inter-individual variability in chronic pain after successful treatment of inflammation remains elusive. We have shown that activation of TRPV1+ colonic nociceptors is essential for the establishment of persistent pain in DSS colitis. Nociceptor development coincides with microbial colonization, while early life dysbiosis can lead to visceral hypersensitivity in adulthood. Whether the microbiota dictates nociceptor development and pain susceptibility remains unknown. Here we test the hypothesis that the microbiota programs nociceptor specification during early development, rendering them more susceptible to sensitization later in life. We have identified the aryl hydrocarbon receptor (AHR) that senses bacterial-derived metabolites as a candidate target that orchestrates transcriptional regulation in nociceptors.We investigated the developmental regulation of nociceptors by the microbiome and how it influences pain sensitivity. We will determine the effects of AHR activation on nociceptor lineage and function as well as the long term impact of AHR signaling on pain sensitivity.We have developed a germ-free (GF) TRPV1-GFP reporter mouse that was used to phenotype and visualise TRPV1+ nociceptors in the absence of a microbiota. We will isolate TRPV1+ neurons by FACS to identify genes that are under the control of the microbiota and to characterise the phosphoproteome of TRPV1+ nociceptors in GF conditions. Finally, we will investigate the role of AHR signaling in nociceptors both acutely and during development.We showed a reduction in thermal pain threshold and a reduction in capsaicin test responses in GF mice. The number and size of DRG neurons was unchanged in GF mice. Examination of molecular markers for peptidergic (CGRP) and non-peptidergic (IB4) neurons did not show a difference. Finally, there was no difference in the expression of TRPV1, suggesting post-translational modification of the channel. In cultured DRG neurons, we found a decrease in capsaicin induced action potentials and a decrease in the amplitude of the capsaicin response in GF mice. Using RNAscope, we showed that TRPV1+ neurons express AHR.Our results highlight the importance of bacterial composition in regulating the development of nociceptors and pain sensitivity in adulthood. Furthermore, we are the first to demonstrate the expression of AHR in sensory neurons. These findings point to a role of the microbiota in programming nociceptors during development. My work will advance our understanding of the role of commensal bacteria in regulating pain and could lead to recommendations for the treatment of neonates in early life to reduce their risk of developing chronic pain later in life.CAG, CIHR