Chronic hyperglycemia is caused by diabetes mellitus-committed genital morphophysiology, and oxidative stress is one of the main factors involved in this process. Alpha lipoic acid (ALA) can prevent metabolic and morphological changes in diabetic individuals. In present study, we evaluated the effects of regular ALA consumption on the spermatogenesis and histoarchitecture in the male genital system of diabetic rats. Thirty-two Wistar rats were divided into groups: Control (CG); Diabetic Control (DCG), receiving commercial diet: ALA Group (ALAG) and Diabetic ALA Group (DALAG), fed diets with added ALA (300 mg/Kg bw). The diabetic groups received a single injection of streptozotocin (60 mg/kg). After sixty days of the diet, the animals were euthanized, and semen, testis and epididymis samples were collected. A histomorphometric analysis was performed to determine the epithelial height, tubular and luminal diameter, tubular and luminal area of seminiferous tubules and each epididymal region. Sertoli cells were evidenced using the antivimenti antibody and were quantified. The results were statistically analyzed by the ANOVA test. At the end of the experiment, the DALAG glycemia was significantly lower than DCG. The histomorphometric parameters of the seminiferous and epididymal tubules did not show improvement in the DALAG. However, there was an improvement in the DALAG in terms of the concentration, motility and percentage of spermatic pathologies, as well as in the number of Sertoli cells (p<0.001). The results demonstrated that supplementation with the ALA antioxidant retards testicular lesions and preserve the process of spermatogenesis in diabetes. Diabetes mellitus (DM) is a globally-known metabolic disorder characterized by chronic hyperglycemia and triggering systemic complications, among them cardiovascular diseases, nephropathies, and neuropathies , 2. The Testicular morphological changes as a consequence of the hyperglycemic effect of DM have been documented . The effAlpha lipoic acid (ALA) is known as a potent natural antioxidant with promising therapeutic applications, capable of restoring endogenous antioxidants (vitamins C and E), chelating free metals, and repairing oxidized proteins . It is uSupplementation with antioxidants has been fundamental to prevent oxidative damage triggering reproductive dysfunction  and reveKnown for its potential in regenerating other antioxidants like vitamin C and vitamin E , ALA hasRattus norvegicus albinus variety, also known as Wistar, were kept in individual cages in the experimental animal room with relatively humid environments of 21–23ºC with 60% humidity, clear and dark cycle control, and water provided ad libitum.The procedure with animals was approved by the Statistical Committee for the Use of Animals of the Federal Fluminense University (protocol CEUA-UFF number 799/16). All procedures followed the norms of the National Research Council (US) Institute for Laboratory Animal Research. Adult male rats of the Thirty-two rats  of streptozotocin  at a dose of 60 mg/kg . Normal The experimental diet was prepared in the Laboratory of Experimental Nutrition (LabNe) of UFF. The control groups consumed pelleted commercial feed  . ALAG anAfter confirmation of diabetes by STZ induction the weight and glycemia of all the animals was measured. Establishing the 5-hour fasting period, the blood was punctured through the caudal vein and analysed with the Accu-Check Perfoma  glycometer  weekly uAfter 60 days of consumption, the rats were euthanized with ketamine 75 mg/kg) along with xylazine (10 mg/kg). Immediately after the sacrifice, both testes and epididymis were collected. The tail of the right epididymis was sectioned and washed with 1mL of powdered milk thinner . Then a  mg/kg alThe left testicles and epididymis were separated. The testes were cleaved transversally and the epididymis longitudinally for visualization of the epididymal regions . The samSections stained with hematoxylin and eosin, visualized on an optical microscope coupled to a digital camera, were obtained from analysis and quantification of the seminiferous and epididymal tubules. Fifty seminiferous tubules were captured after the selection of the most rounded tubules according to Leblond and Clermont’s criteria . From thThe tubule area was verified by delimiting the tubule in the basal membrane (TA) and bypassing the seminiferous tubule spermatids (LA). The TD and LD were measured using the average of two perpendicular lines. The EH was evaluated by the mean of four measurements in the epithelium .Immunolabeling for mapping Sertoli Cells with an anti-vimentin monoclonal antibody (mouse 1:100)  was associated with the EnVision FLEX development system using 4 μm thick histological slices on salinized slides. The cuts were submitted to the automated process of dewaxing, hydration, and antigenic recovery in a single step in the PTLink Dako PT100 equipment. Then, the cuts were circled by the DAKO S2002 hydrophobic pen to prevent the diluted antibody solution from flowing. Subsequently, the slides were dehydrated in alcohol with increasing concentrations and submitted to four xylol baths. The slides were assembled with ALLKIMIA Synthetic Canada Balm for further microscopic analysis.plugin of the Image J program. The mean number of cells counted per tubule of each experimental group was calculated according to the method proposed by Corrêa et al. . Unlike DALAG, at week 8, hyperglycemia was not statistically significant compared to the beginning of the experiment. According to Observed in the STZ-induced groups, there was a marked decrease in tubular diameter, desquamation of germ cells, and agglomeration of cells in the tubular lumen . In the The groups induced by STZ presented a significant decrease compared to the control groups in the parameters of the total and luminal areas, including the total and luminal diameters (p<0.001) of all epididymal regions. There was no significant change in epididymal tubules between DALAG and DCG .According to Sertoli cells were evidenced by the immunohistochemical labelling of vimentin . The diaThe induction of DM by streptozotocin was efficient in establishing pathological lesions affecting spermatogenesis. Chronic hyperglycemia is the main cause of increased production of ROS that favours tissue oxidative damage and may lead to sexual dysfunction . AntioxiInduction of diabetes by streptozotocin was confirmed in diabetic groups (>270mg/dL). Hyperglycemia was evaluated throughout the experiment and, at the end of 8 weeks, the supplemented rats presented an attenuation of the serum level compared to the first glycemic measurement. The diabetic group supplemented with ALA had lower final hyperglycemia than the control diabetic group. This data agrees with Mohasseb et al.  that shoHistopathological changes were observed and evidenced in testicular histomorphometry in diabetic groups after induction by streptozotocin caused by free radicals. Kaplanoglu et al.  submitteRegarding epididymal regions, the histomorphometric analysis showed tubular decrease of all epididymal regions influenced by diabetes. Similar results were observed by Soudamani et al. , who repThe damage of diabetes on sperm parameters is similar to previous studies . Alpha lThe expression of vimentin is found in Sertoli cells associated with membrane integrity. Xu et al.  observedDM is a disease known worldwide for compromising reproductive physiology. Our results suggest that oral ALA supplementation attenuates the loss of Sertoli cells and improves the concentration and sperm motility affected by diabetes.


Adult-acquired flatfoot deformity is a progressive flattening of the arch of the foot that results from posterior tibial tendon insufficiency with a predilection for middle-aged women. A lateralized force vector associated with hindfoot valgus in adult-acquired flatfoot produces lateral ankle pain due to impingement at the lateral hindfoot, which can even lead to stress fractures of the distal fibula. Here, we present the rare case of a 73-year-old woman who presented with stress fractures of the bilateral taluses and unilateral distal fibula accompanied by severe adult-acquired flatfoot deformities. Adult-acquired flatfoot deformity is a progressive flattening of the arch of the foot that results from a combination of posterior tibial tendon insufficiency and failure of the capsular and ligamentous structures of the foot. A variety of symptoms can accompany this deformity depending according to its progression including pain and swelling along the course of the posterior tibial tendon, a heavy or tired feeling in the foot, difficulty walking or standing, painful calluses on the sole, and pain in the lateral ankle . LateralA 73-year-old woman presented with the complaint of left ankle pain that had exacerbated with walking for the previous month. She had a limping gait and complained of a limited walking ability of 5–10 minutes with a cane because of pain. She originally had limited walking ability due to a cerebral infarction 10 years prior that was classified as least-limited community walker according to the classification by Perry et al. ; howeverAn anteroposterior (AP) weight-bearing view of the left ankle joint revealed the fracture of the distal fibula, valgus talar tilt with joint space narrowing at the lateral tibiotalar joint, and collapse of the lateral talar dome . An AP wShe could not recall any trauma or unusual activity that may have caused this problem. She denied any history of smoking, alcohol abuse, or corticosteroid use. A blood test was negative for rheumatoid factor, anticyclic citrullinated peptide antibody, and antinuclear antibodies. Radiographs of other joints including the hip, knee, and shoulder revealed no osteonecrosis. Dual-energy X-ray absorptiometry measurements showed that the bone mass was 82% of young adult mean (YAM) in the lumbar spine and 81% of the YAM in the femoral neck without any use of drugs affecting bone metabolism, which did not meet the criteria for osteoporosis.The fibular stress fracture was treated successfully in 2 months with a walking boot and limited weight-bearing with crutches. After the fibular stress fracture healed, the patient could perform her activities of daily living as before the fibular fracture without wearing any devices or using any analgesics for pain control. At the time of the most recent follow-up, 2 years after the first visit to our hospital, the patient maintained the performance described above without complaint, although the comminuted lateral talar body displayed nonunion on radiography and CT evaluations.Stress fractures refer to fractures caused by mismatched bone strength and repetitive stress placed upon a bone. These fractures can be further divided into two types: fatigue fracture resulting from abnormal stresses on normal bone and insufficiency fracture resulting from normal stresses on abnormal bone. The foot and ankle are the most common locations of stress fracture, and the prevalence is highest at the tibia, calcaneus, and metatarsals, followed by the navicular, fibular, medial malleolus, and other tarsal bones , 6. The Valgus hindfoot alignment has been demonstrated to result in the lateralization of the force vector in some cadaver studies , 19. FriWhen stress fracture is suspected, plain radiograph should be the first imaging modality considered because of its availability and low cost. However, stress fractures of the talus may be difficult to diagnose on radiographs especially in the early stages without displacement of the bone fragment . The valThe talus is predisposed to avascular necrosis, mainly after traumatic fractures due to its nature of a wide range of articular cartilage coverage around 60%, no muscular or tendinous attachments, and small nutrient vessels . AlthougIn conclusion, a stress fracture of the talus may be provoked in adult-acquired flatfoot deformity. The repetitive shearing force placed on the talus due to the lateralization of the load axis in the fixed hindfoot valgus is considered the pathology of this condition.


Although most older adults live outside of care institutions, not all seniors choose to live in traditional family homes. Among those who relocate, some relocate too early while others are pre-frail or frail when they relocate. Social frailty – the interaction between social vulnerability and frailty – could contribute to these untimely relocations. The goal of this study was to inform the concept of social frailty by examining a population of semi-independent older adults who recently relocated to a continuum of care community. The objectives of this study were to: 1) understand the influence of the social determinants of health on the relocation process; 2) explore whether relocation increases or reduces social frailty; and 3) measure the level of post-relocation frailty in study participants. This mixed method study combined semi-structured interviews on the relocation process, the frailty identification tool PRISMA-7, and socio-demographic surveys. Twenty-nine recently relocated seniors were recruited with the assistance of a Citizens' Advisory Committee along with advertisements, presentations, information booths, and word of mouth. Qualitative descriptive thematic analysis and descriptive statistical analyses were used to examine the relationship between frailty, socio-demographic variables and relocation. Findings indicated that several social determinants contributed to frailty and that relocation into a continuum of care community could mitigate some aspects of social frailty. A conceptual framework on the influence of social frailty on relocation is discussed. More research is needed to inform the concept of social frailty and to better understand the impact of social factors on frailty.


This paper proposes and tests a multilayer framework for simulating the network dynamics of inter-organizational coordination among interdependent infrastructure systems (IISs) in resilience planning. Inter-organizational coordination among IISs  would greatly affect the effectiveness of resilience planning. Hence, it is important to examine and understand the dynamics of coordination in networks of organizations within and across various systems in resilience planning. To capture the dynamic nature of coordination frequency and the heterogeneity of organizations, this paper proposes a multilayer network simulation framework enabling the characterization of inter-organizational coordination dynamics within and across IISs. In the proposed framework, coordination probabilities are utilized to approximate the varying levels of collaboration among organizations. Based on these derived collaborations, the simulation process perturbs intra-layer or inter-layer links and unveils the level of inter-organizational coordination within and across IISs. To test the proposed framework, the study examined a multilayer collaboration network of 35 organizations from five infrastructure systems within Harris County, Texas, based on the data gathered from a survey in the aftermath of Hurricane Harvey. The results indicate that prior to Hurricane Harvey: (1) coordination among organizations across different infrastructure systems is less than the coordination within the individual systems; (2) organizations from the community development system had a low level of coordination for hazard mitigation with organizations in flood control and transportation systems; (3) achieving a greater level of coordination among organizations across infrastructure systems is more difficult and would require a greater frequency of interaction (compared to within-system coordination). The results show the capability of the proposed multilayer network simulation framework to examine inter-organizational coordination dynamics at the system level . The assessment of inter-organizational coordination within and across IISs sheds light on important organizational interdependencies in IISs and leads to recommendations for improving the resilience planning process. Natural hazards  pose great threats to infrastructure systems that support the well-being of society. Resilience, the “ability to prepare and plan for, absorb, recover from or more successfully adapt to actual or potential adverse events” is regarded as an important capacity of a city or a community facing stressors ,2. HenceResilience planning involves coordination of multi-organizational processes across IISs . ContradThe planning background in Houston also highlights the necessity of examining and understanding inter-organizational coordination dynamics within and across IISs for better resilience planning. Houston is one of the most flood-prone city in the nation. One important reason contributing to flood vulnerability in Houston is the confliction between the rapid urban development and poor urban planning with underinvestment in flood control infrastructure systems . HoustonFor example, this insufficient integration among plans (due to inadequate coordination among actors) was problematic and led to vulnerability during Hurricane Harvey. In August 2017, Hurricane Harvey hit Houston Texas, and caused an estimated $125 billion in damage . One of Interdependencies among IISs is an important aspect of coordination in the resilience planning process. While several studies have examined the interdependencies among IISs, the majority of the existing literature primarily focuses on physical aspects –16, and While SNA informs about the structural properties of inter-organizational networks ,23, therConsidering these factors, this study proposes a network simulation process to capture the varying levels of interaction frequencies among organizations and employs a multilayer network approach to representing the coordination between organizations of IISs. We convert the collaboration at varying levels of frequency among organizations to the link probability in the network representing the likelihood that collaboration may happen among organizations. Accordingly, perturbations in the links of the network (based on their coordination probabilities) are used to simulate the dynamics of inter-organizational coordination during a time period . The changes in network-level measures after link perturbation is then used to evaluate coordination performance. The existing literature has specified the common procedure for network characterization based on evaluating network performance: (1) obtaining empirical data to map a network; (2) measuring the investigated network’s features; (3) conducting link or node perturbation in the network ; (4) assThe majority of studies regarding infrastructure systems employing network modeling focused primarily on physical interdependencies among IISs. In addition, most of these studies did not fully consider the interactions among organizations managing and operating these systems  ,28,31,32The proposed framework conceptualizes the inter-organizational coordination among IISs embedded in urban systems as a multi-layer network. Each layer represents a specific infrastructure system  and nodes represent organizations. In terms of hazard mitigation in resilience planning, inter-layer links represent inter-organizational coordination within systems and intra-layer links represent coordination across systems. The simulation process perturbs inter-layer and intra-layer links based on their coordination probabilities (determined based on varying levels of collaboration frequency) within and across IISs. Accordingly, the inter-layer and intra-layer coordination level are determined using two measures related to network global efficiency. The details related to different steps of the proposed framework are discussed in the following section using a case study of Houston area, Texas, prior to Hurricane Harvey.In the months or years prior to Hurricane Harvey, to the best of your knowledge, did you or any other employee from your organization collaborate or work directly with any of the organizations listed below on hazard mitigation efforts? If so, how frequently have such collaboration occurred ?” The survey was sent to stakeholders in February 2018 and concluded with a total of 198 individual responses representing 160 distinctive organizational departments.The city of Houston, Texas, is used as our study site to show application of the proposed framework. We conducted a survey of stakeholders in Harris County, Texas, to collect data regarding collaboration of hazard mitigation in resilience planning among organizations in different infrastructure systems . After Hurricane Harvey in 2017, we identified 95 relevant organizations from five different infrastructure systems: transportation, flood control, emergency response, community development, and environmental conservation. We included these organizations in the survey as a roster of potential organizations with which survey respondents collaborated before Hurricane Harvey. We asked survey respondents about the frequency of hazard mitigation collaboration in resilience planning that occurred prior to Hurricane Harvey. We established the collaborative relationship through following survey questions: “Based on the gathered information regarding collaboration of hazard mitigation in resilience planning between organizations, we mapped two-mode  collaboration networks at different levels of collaboration frequencies . Due to the nature of survey questions, relationships between organizations within the original survey roster and among the survey respondent organizations could not be determined. In consideration of this, we selected 35 organizations which were both in the survey roster and among the survey respondents to map the collaboration network. To understand inter-organizational coordination within and across different infrastructure systems, we categorized these 35 organizations into five infrastructure systems: flood control, emergency response, transportation, community development, and environmental conservation. The proposed framework comprises four main steps: (1) conceptualize inter-organizational coordination among IISs as a multilayer network; (2) determine coordination probabilities between organizations based on the reported frequency; (3) perturb links based on assigned coordination probabilities; and (4) evaluate the network performance after link perturbation using measures such as network efficiency and coefficient of variation. These steps are elaborated in the remainder of this section.The proposed framework conceptualizes coordination among organizations from different infrastructure systems as a multi-layer network. Each layer in the multi-layer network represents one infrastructure system. Intra-layer and inter-layer links of the multilayer network represent inter-organizational coordination for hazard mitigation in resilience planning within and across IISs. Network simulations requires the probability of node  or link  perturbation as input. But these mathematical probabilities are usually difficult to obtain directly. For example, coordination between organizations is often stated in frequency terms such as daily or weekly. Therefore, we use probability distribution to convert different levels of collaboration frequency  to the coordination probability of each link. We are able to obtain these levels of collaboration frequency from survey responses.In the proposed framework, to determine coordination probabilities, we define daily interaction among organizations as the baseline, in which the probability of coordination between two organizations would be equal to one. We make the following assumptions to determine the daily coordination probability for other levels of collaboration frequency.We approximate the probability distribution of coordination frequency as a normal distribution;We define the boundaries for each frequency level . The boundary for weekly collaboration is from once a week to seven times a week  considering seven days one week. The boundary for monthly collaboration is from once a month to four times a month  considering that one month has 4 weeks. Likewise, considering that one year has 12 months, the boundary for the yearly collaboration is from once a year to 11 times a year . Finally, we consider daily frequency should have interaction at least once a day . The boundaries of each collaboration frequency are listed in We treat holidays and weekends with the same weight as other days when determining coordination probabilities as they will not affect the simulation result, but unnecessarily, complicate the process.Based on these assumptions, the daily coordination probability for organizations which reported a weekly interaction frequency is determined as an average of 96 days per year  with a 95% confidence that the coordination frequency is in the interval of , 144  between the organizations. First, we generate a random probability between 0 and 1 (0 and 1 themselves are excluded) in each iteration of the simulation process. Meanwhile, each link will randomly draw a sample among 100,000 generated samples for the assigned distribution. If the selected sample is less than the generated probability, the link is removed in this iteration of the simulation process. This probabilistic perturbation process means that the lower the daily coordination probability of the link is, the higher probability the link will be removed in the simulation process. For example, if the daily coordination probability of a link is 1 , the link would never be removed in the simulation process. We conduct the simulation process with 365 iterations to capture the inter-organization coordination fluctuation in a full year cycle. In the case of investigating the inter-organizational coordination within a specified infrastructure system, we only remove the correspondent intra-layer links. Accordingly, we only remove inter-layer links when examining the inter-organizational coordination across infrastructure systems. That means, if we want to investigate the inter-organizational coordination within the flood control system, we only remove the links within the flood control system ; when we want to analyze the inter-organizational coordination across the flood control and transportation systems, we only remove the links between these two systems  in the simulation process. This separate link removal enables examining the level of coordination within and across different systems separately.N represents the total number of nodes in the network and dij is the distance of the shortest path between node i and j. Network efficiency is very sensitive to the total number of nodes  in the network [σ and μ are the standard deviation and mean of the network efficiency of multiple iterations. This measure implies the stability of coordination during the simulation process.We adopt two measures for examining the level of coordination within and across IISs: network efficiency and its coefficient of variation after the link perturbation. Network efficiency measures the shortest distances between nodes after the link perturbation. The shortest distances between nodes tend to increase as links are removed, and the increase of distances between nodes can be interpreted as the decrease in the overall level of coordination among various organizations of IISs –38. Netw network . As a reIn order to evaluate the extent to which variation in daily coordination probability between organizations affects overall level of coordination, we examined five scenarios in which we uniformly assigned five different daily coordination probabilities  to each link in the mapped multi-layer network.To examine how to increase coordination within and across different systems, we conducted simulation experiments to determine the required coordination probability of links to achieve targeted network efficiency within and across different infrastructure systems. The first step is to uniformly assign each link an initial coordination probability: 1/365. Then the simulation process would be applied within or across different infrastructure systems, and network efficiency is calculated after simulation iterations. If the targeted network efficiency is not met, the coordination probabilities of links are increased by 1/365 increment until the targeted network efficient is met. In this section, we show the application of the proposed framework to the data collected from the stakeholder survey in Harris County, Texas. Each infrastructure system is mapped to one layer of the multi-layer network. The layer of flood control system has 15 nodes  and 79 links representing coordination between organizations in terms of hazard mitigation. The transportation layer comprises 13 nodes and 57 links, while the community development layer has 16 nodes and 74 links. The emergency response layer and environmental conservation layer have 13 nodes with 56 links and 14 nodes with 63 links, respectively. The total number of nodes in the five infrastructure systems is 71, which is more than the total number of organizations, 35. This is because some organizations, such as City of Houston, American Planning Association, and-Galveston Area Council, have multiple departments involved in different infrastructure systems, and therefore appear in more than one layer.The simulation results indicate that the lowest daily coordination probability for each link, 15% in this case, leads to the lowest mean of network efficiency (0.355) and the highest coefficient of variance 0.116). The scenario with the highest daily coordination probability for each link, 75%, leads to the highest mean of network efficiency (0.725) and the lowest coefficient of variance (0.009). . The sceAs shown in As illustrated in To study how to increase inter-organizational coordination within and across different infrastructure systems, we set the targeted network efficiency as half of the maximum values and applied the coordination increase simulation to calculate the required coordination probability. Tables Tables The results of the multi-layer network simulation framework examine inter-organizational coordination in IISs for flood hazard mitigation in Harris County. The discussion of the results below focuses on how the level of inter-organizational coordination within and across IISs may affect resilience planning outcomes. We provide anecdotal evidence and link to other studies to reinforce the validity of the findings obtained from the multilayer network simulation framework.As shown by the results, the maximum network efficiency within different infrastructure systems are close (around 0.85), which implies that different infrastructure systems have almost the same potential to reach the same level of within-system coordination. However, the actual coordination for each system varies based on the collaboration frequency obtained from the survey, with the highest level of coordination (transportation: 0.46) being almost twice that of the lowest (community development: 0.25). The transportation system has the highest network efficiency and the lowest coefficient of variance after the intra-link perturbation, implying that prior to Harvey, organizations within the transportation system had a higher level of coordination with each other compared to organizations in other infrastructure systems.The flood control and emergency response systems have the second highest network efficiency and the second lowest coefficient of variance for within-system coordination. Also, the flood control system has the highest maximum network efficiency. The flood control and emergency response systems also had relatively high levels of coordination for hazard mitigation prior to Harvey. The flood control system plays an important role in hazard mitigation and resilience planning. Organizations such as Harris County Flood Control District and Texas Floodplain Management Association within the system are usually responsible for floodplain management and hazard mitigation plan and policy development . Sufficient inter-organizational coordination within the flood control system would be an important foundation for hazard mitigation integration in resilience planning . OrganizThe network efficiency within the community development system is the least, and it also has the lowest maximum network efficiency. One possible reason is that there is a lower level of coordination among organizations within the community development system compared to other infrastructure systems in Harris County. This finding suggests that organizations within the community development system do not fully engage in hazard mitigation processes. Coordination for hazard mitigation among organizations in the community development system is crucial for resilience planning ,10. HoweThe simulation results show that the level of coordination across different infrastructure systems is much lower than the coordination level within infrastructure systems. Also, the maximum network efficiency across systems is lower than those within the infrastructure systems. This means that inter-organizational coordination for hazard mitigation across infrastructure systems is harder to achieve a high level compared to within-system coordination. The highest level of coordination within the system (transportation: 0.46) is nearly 1.6 times more than the highest one across systems (transportation and emergency response: 0.28). Organizations in the emergency response system have a high level of coordination for hazard mitigation with organizations in the transportation system indicated by the highest cross-system network efficiency and lowest coefficient of variance. This could be due to the importance of transportation infrastructure  in emergency response operations (such as evacuation and relief supply). For example, many roads in Houston were flooded with water more than 25 inches deep during hurricane Harvey, preventing access by fire vehicles. Firefighters had to manage rescues by boat, greatly decreasing rescue efficiency.The results also show that organizations in the flood control system have a low level of coordination with organizations in the community development system. Also, inter-organizational coordination for hazard mitigation between community development and transportation systems is the lowest despite the high maximum network efficiency. This finding suggests that organizations from the community development system had insufficient coordination for hazard mitigation with organizations in other infrastructure systems prior to Hurricane Harvey.n2, where n is the number of nodes in the network). However, when the maximum network efficiency is low, it requires great coordination frequency to increase the network efficiency.The results indicate two ways to increase the level of inter-organizational coordination within and across systems: (1) increasing maximum network efficiency, and (2) increasing coordination probabilities. In the context of resilience planning, these two methods essentially suggest establishing new collaborations or increasing coordination frequency among organizations. Maximum network efficiency relates to the number of the shortest paths in networks. Basically, for the same network, a network of greater density implies higher maximum network efficiency . This imIn summary, to increase the level of inter-organizational coordination within and across IISs, the findings suggest establishing new interactions among organizations when the existing collaboration is small and limited, especially with organizations involved in more than one infrastructure system . Forums and workshops in which diverse actors could participate are considered an effective way to establish new interaction regarding resilience planning . Also, oAlthough the planning background in Houston and the example of Hurricane Harvey suggest that more coordination among IISs would have enhanced outcomes in resilience planning, it is important to note that a body of literature highlights that there are often tradeoffs and unintended consequences of higher connectivity and coordination in networks –53. ChelThis paper proposes and tests a multilayer framework for simulating the network dynamics of inter-organizational coordination among IISs in resilience planning. The proposed framework and its application in the context of Harris County, Texas, prior to Hurricane Harvey have multiple methodological and theoretical contributions. First, the presented work considers the organizational aspects of interdependencies among IISs, departing from the majority of infrastructure interdependency studies which mainly focus on physical aspects. Second, the proposed framework adopts the simulation process and multilayer network for examining human/organizational networks with heterogenous types of nodes and dynamic links. The proposed framework enables modeling inter-organizational coordination among IISs with heterogenous nodes and capturing the coordination frequency among the nodes. Third, the framework provides new insights into coordination dynamics among organizations within and across different systems. Fourth, from the practical perspective, the framework enables examining the coordination increase strategies and provides recommendations to increase the level of coordination among organizations, which may lead to better resilience planning in IISs.Some limitations in the proposed framework still exist which can be addressed in future research. This study assumes that coordination frequency is normally distributed. Future studies can further test this assumption by estimating the coordination probability based on the longitudinal data gathering regarding interaction frequencies. Such data collection would require more specific data regarding the dates and mode of coordination interactions among agencies, a task whose implementation would not be straightforward. Also, in the simulation experiments for examining the coordination increase strategies, we increased the same coordination probability for all links in the scenarios (1/365 in each iteration). The future work could examine the increase in coordination probability based on different network reticulation mechanisms, such as preferential attachment. Furthermore, inter-organization networks directly and indirectly influence the networks of plans, as well as infrastructure networks. A low level of coordination in inter-organizational networks may lead to conflicting plans and more vulnerability in physical networks. Hence, understanding the interdependencies among inter-organizational networks, network of plans, and physical networks may hold the key to unlocking a holistic resilience planning process in IISs.


Varroa destructor infestation rates (organic apiary). We found that the biological age of bees from the conventional apiary progressively decreased from the spring (17 days) to the fall (6 days). However, in colonies from the organic apiary, the population aged from spring (13 days) to summer (18.5 days) and then rejuvenated in the fall (13 days) after Varroa treatment. Biological age was positively correlated with the amount of brood (open and closed cells) in the apiary with low Varroa pressure, and negatively correlated with Varroa infestation level in the apiary with high Varroa pressure. Altogether, these results show that the estimation of biological age is a useful and effective method for assessing colony demographic state and likely detrimental effects of stress factors.Honeybee colonies are increasingly exposed to environmental stress factors, which can lead to their decline or failure. However, there are major gaps in stressor risk assessment due to the difficulty of assessing the honeybee colony state and detecting abnormal events. Since stress factors usually induce a demographic disturbance in the colony , we suggest that disturbances could be revealed indirectly by measuring the age- and task-related physiological state of bees, which can be referred to as biological age . We therefore estimated the biological age of bees from the relationship between age and biomarkers of task specialization (vitellogenin and the adipokinetic hormone receptor). This relationship was determined from a calibrated sample set of known-age bees and mathematically modelled for biological age prediction. Then, we determined throughout the foraging season the evolution of the biological age of bees from colonies with low  or high  As eusocial insects, honeybees live in societies that are notably characterized by an age-dependent division of labor among workers for tasks related to colony homeostasis, growth and development . Bees geHowever, in a rapidly changing environment, honeybee colonies are increasingly exposed to diverse sources of stress, which represent a challenge to their social homeostasis and can ultimately lead to their collapse , 13. A mThe nurse/forager ratio is crucial to colony functioning and colonies generally respond to perturbations via the plasticity of the division of labor . For instance, a significant loss of foragers for the colony will accelerate the behavioral maturation of young bees to replace them . SimilarVarroa destructor, the greatest threat to colonies worldwide ;  [The expression levels of ATGTGGTA .Varroa infestation) in relation to the sampling dates were analyzed via generalized linear mixed effect models (GLMM) by maximum likelihood using the lme4 package. The colony was considered as a random variable. Generalized linear hypothesis tests as implemented by the multcomp package allowed for multiple comparisons between the different time points. The link between biological age and colony parameters was determined using a linear regression analysis.All statistics were run using the R statistical software. The codes for the age-biomarker model and the ABC procedure are available in vg significantly changed with age . It increased sharply after bee emergence, stabilized until day 10 and then decreased until day 20, from which time it remained stable . In the organic apiary, the infestation level exhibited an earlier and more severe increase until treatments were performed (mid-August for both apiaries).We then analyzed variations in colony parameters that could be associated with variation in population biological age. Apart from pollen storage in the conventional apiary, each colony parameter changed significantly over the season . In bothr2 = 0.514 and closed brood cells: r2 = 0.579, p < 0.001 for both; Varroa infestation . However, in the organic apiary, the biological age of the colony population was positively correlated with the Varroa infestation level .In the conventional apiary, between April and October, the predicted biological age of the colony population was positively correlated with the amount of brood , nurse bees might accelerate their behavioral development and forage precociously in response to a loss of foragers or exposure to disease , 16–18, elopment , 26, areelopment . Since celopment , identifelopment .i.e. a higher proportion of foragers at the colony level) to sustain the needed resources for consumption by the colony. Conversely, Varroa infestation level and the amount of stored honey were negatively correlated with population biological age. This seems counter-intuitive given that Varroa infestation is known for decreasing the level of vitellogenin of individual bees [Varroa infestation rate in the fall is associated with a decrease in vg level [Varroa infestation levels remained low and mostly below 5% throughout the foraging periods and therefore it is possible that the influence of Varroa remained negligible when compared to the influence of the brood. The negative correlation would simply be due to the concomitant growth of the Varroa population and a decline in population biological age between spring and fall. A similar explanation could be advanced regarding the link between the amount of stored honey and the biological age of colonies.In the conventional apiary, a regular decrease in the biological age of colony population was observed between the spring and fall. This observation is consistent with a normal colony life cycle and the changes occurring between foraging periods. At the end of the foraging period , short-lived summer bees are replaced by long-lived winter bees until the next foraging period (spring). The physiological features of winter bees resemble those of nurse bees, with high levels of nutrient storage and vitellogenin , 45, untual bees , 49, andvg level , 32. HowVarroa on the vitellogenin titer of bees (see above). Indeed, in the organic apiary the Varroa infestation level strongly increased until treatments (mid-August). Our data indicates also that a high level of Varroa could overcome the influence of other colony parameters like the amount of brood, and therefore prevent the colony from adapting its population demography to its needs. However, since only one apiary per experimental condition was used , we cannot exclude that variations in colony demography were due to environmental factors (rather than to Varroa infestation level). Finally, a negative correlation between the amount of stored pollen and colony biological age was also identified. This could reflect the positive influence of pollen nutrition on vg level and therefore the development of a nurse physiological profile [Interestingly, we did not observe a decrease in population biological age in the organic apiary. On the contrary, the average biological age increased between April and August, and rebounded to its initial level in the fall. This abnormal population dynamic could be largely explained by the direct influence of  profile , 50.Our data demonstrated that the biological age of bees can objectively be assessed by measuring biomarkers that are related to the age-dependent division of labor, and thus could be useful for the longitudinal monitoring of colony demography and health. We therefore believe that the ability to gather biological age information in monitoring programs will help to better understand how honeybees respond or adapt to growing environmental pressures. At the same time, further studies, which include larger calibration sample sets  and combinations of more biomarkers, will improve the predictive power and accuracy of biological markers.S1 File(R)Click here for additional data file.S2 File(XLSX)Click here for additional data file.S1 FigExpression levels of vitellogenin (A) and the receptor to adipokinetic hormone (B) as a function of bee age. The solid lines denote the average expression levels (n = 12 pools per sampling age); the dotted lines give the 95%-confidence envelopes of the expression levels with the over-dispersion parameter c equal to 0; the dashed lines give the 95%-confidence envelopes of the expression levels with the over-dispersion parameter c equal to 1 .(TIFF)Click here for additional data file.


The integration of both conventional and digital techniques in the treatment workflow can have a synergistic effect that facilitates the treatment of complex complete mouth prosthetic rehabilitations.The introduction of digital dentistry and CAD/CAM technology has redefined treatment concepts in implant dentistry—computer guided implant placement has become routine practice, and CAD/CAM prostheses are now commonplace. These advances in treatment options and modalities has led to a paradigm shift in the workflow of surgical and restorative treatments. This case report presents a customized staged treatment protocol that involves the strategic retention of teeth to serve as transitional abutments, which will support a computer guided implant surgical guide as well as a fixed interim prosthesis. The treatment protocol also describes an integrated digital and conventional workflow for full mouth implant-supported fixed prosthetic rehabilitations to provide improved patient care with more predictable outcomes and fewer complications. The challenges involved in the treatment of completely edentulous patients with fixed implant rehabilitations have been reported in the literature ,2,3,4. IOnce the implants are placed in prosthetically idealized positions based on the guided surgical planning, the restorative phase is greatly simplified as the appropriate prosthetic space as well as implant access hole locations have been virtually pre-verified. The combination of CAD-CAM technology with computer guided implant surgery not only simplifies the treatment protocol, but can also enhance the final prosthetic outcome ,16.The transitional period from a provisional to a definitive prosthesis during a complete mouth implant reconstruction presents a challenge for clinicians and patients, alike. Unexpected procedural complexities may hamper the clinician’s progress, and patients may experience difficulty in accepting and adapting to prosthetic changes. Various techniques have been applied to facilitate this transition including the use of removable dentures and provisional mini-implants, as well as immediate implant loading protocols to reduce the treatment duration and enhance the patient experience ,20,21,22The aim of this clinical report is to describe an integrated digital and conventional treatment workflow in the management of a fixed implant-supported complete mouth rehabilitation. A staged treatment approach was utilized in conjunction with computer guided implant placement, and definitive prostheses were fabricated using CAD/CAM titanium abutments and monolithic zirconia prostheses. Before starting the treatment, the subject gave her informed consent that records of the case would be available for teaching purposes, including scientific publication.A 77-year-old female patient presented to the Advanced Graduate Education Prosthodontics clinic at Harvard Dental Center with the chief complaint of “I would like to chew and smile.” The patient requested fixed restorations and expressed a desire to avoid wearing removable prostheses during her treatment. The patient’s medical history was non-contributory to any dental treatment with normal vital signs and a reported allergy to penicillin. The initial comprehensive clinical A and radFollowing a discussion of the benefits, risks and alternative treatment options, the patient consented to maxillary and mandibular fixed implant-supported rehabilitation. Based on the patient’s existing anatomy, the planned prosthetic design, and biomechanical prosthodontic principles, eight implants were planned in the maxillary arch, and six were planned in the mandibular arch. The treatment goals were to restore form, function, and esthetics while maintaining the patient in fixed prostheses throughout the entire treatment period. The first phase of treatment consisted of oral hygiene instruction and elimination of active disease, strategic extraction of teeth and fixed provisionalization. Eight implants were planned in the maxilla at the positions of the lateral incisors, canines, first premolars and first molars, and six implants were planned in the mandible in the areas of the canines, first premolars and first molars. Extraction sites were determined based on the planned implant positions while the remaining abutment teeth were kept to support a fixed provisional as well as the computer guided surgical template during the implant surgical phase A,B. FollThe second phase of treatment involved an integrated digital and conventional workflow for guided implant surgical intervention. Eight weeks after the extractions, radiographic guides were fabricated by duplicating the provisional restorations in a radiopaque acrylic and affixing them to templiX reference plates . Computerized tomography (CT) scans were taken with the patient wearing the radiographic guides stabilized on the transitional abutments. The implant positions were virtually planned in relation to the hard and soft tissue architecture and the planned prostheses A,B with After a three-month healing period, the transitional teeth abutments were extracted A,B. The During the definitive restorative phase, maxillary and mandibular implant level impressions were made with silicone impression material  using an open tray impression technique. The master casts and the existing provisional casts were scanned and superimposed, allowing for the virtual designing of the abutments and zirconia prostheses A,C. CAD/In this case, the transition from failing dentition to a fixed implant-supported complete rehabilitation was accomplished in several phases: Strategic extraction, virtual implant planning, computer guided surgery, and CAD/CAM prosthesis fabrication. Despite advances in the computer guided surgical technology, inaccuracies can accumulate from all stages of the workflow—from CT data acquisition, and data manipulation, to imprecision in the seating of the surgical template. Horizontal fixation pins are commonly used in computer guided implant systems treating edentulous arches. In such cases, however, the reproducible seating of the radiographic guide and surgical template can be a challenge due to the nature of mucosa-borne guided surgery. In the present case, the utilization of transitional tooth abutments allowed for reproducible and accurate positioning of the radiographic and surgical guides. Another benefit of strategically keeping transitional abutments is that quadrilateral positioning of transitional tooth abutments allows for fixed provisional prostheses and uninterrupted healing of the implants. In the final restorative phase, the integration of digital technology with conventional prosthodontic techniques allowed for a customized treatment protocol. The use of a digital impression system for a single implant restoration has been found to be more efficient than conventional impression techniques . HoweverWith the introduction of novel digital technology into the field of dentistry, it is necessary to determine the ideal combination of a digital and conventional workflow based on the stages of treatment. In our proposed protocol, the overall workflow can be largely divided into three phases consisting of integrated conventional and digital techniques. Phase 1 is a diagnostic and preparatory phase wherein conventional techniques are used to set the foundation for future surgical and restorative interventions. The end result of this phase is an idealized provisional restoration on transitional tooth abutments. Phase 2 consists of a conventional conversion of the provisional to a radiographic stent, and a digital planning and subsequent guided placement of the implant fixtures. Finally, in phase 3, a conventional technique is utilized for the final impressions of the implants, while a predominantly digital protocol is utilized to arrive at the final prostheses .A systematic review of implant supported fixed prostheses reported complications such as the fracture of resin teeth or frameworks, material wear, and veneer chipping or fracture . The useThe overall expected prognosis of the presented treatment is considered good with patient compliance in the wearing of an occlusal guard and following a proper recall and maintenance regimen.With adequate planning and proper execution, a phased computer-guided implant surgical protocol and CAD/CAM technology can bring accuracy, efficiency, and predictability to complex full-mouth implant rehabilitation cases. Understanding the limitations of conventional and digital dentistry will allow the clinician to create a synergistic integration of processes from both realms to optimize the management of complex and challenging treatments.


Brain imaging methods have contributed to shed light on the mechanisms of recovery after early brain insult. The assumption that the unaffected right hemisphere can take over language functions after left perinatal stroke is still under debate. Here, we report how patterns of brain structural and functional reorganization were associated with language outcomes in a group of four-year-old children with left perinatal arterial ischemic stroke (PAIS). Specifically, we gathered specific fine-grained developmental measures of receptive and productive aspects of language as well as standardized measures of cognitive development. We also collected structural neuroimaging data as well as functional activations during a passive listening story-telling fMRI task and a resting state session (rs-fMRI). Children with a left perinatal stroke showed larger lateralization indices of both structural and functional connectivity of the dorsal language pathway towards the right hemisphere that, in turn, were associated with better language outcomes. Importantly, the pattern of structural asymmetry was significantly more right-lateralized in children with a left perinatal brain insult than in a group of matched healthy controls. These results strongly suggest that early lesions of the left dorsal pathway and the associated perisylvian regions can induce the interhemispheric transfer of language functions to right homolog regions. This study provides combined evidence of structural and functional brain reorganization of language networks after early stroke with strong implications for neurobiological models of language development. The prevalent theories explaining the functional recovery of language functions after perinatal ischemic stroke strikingly differ on the role of perilesional functionally spared regions as opposed to the homologous non-affected contralesional brain areas. Here, we assessed how patterns of brain functional and structural reorganization were associated with language outcomes in a group of four-year-old children with left perinatal arterial ischemic stroke (PAIS). Larger lateralization indices of both functional and structural connectivity toward the right hemisphere were associated with higher levels of language development. Thus, interhemispheric plasticity through structural and functional hyperconnectivity mechanisms might be crucial in early damage, probably through the degeneration of neurons projecting from temporal to frontal areas together with contralateral axonal sprouting over the right hemisphere.In adults, language processing relies on a largely distributed network mainly involving perisylvian brain regions in the left hemisphere . These bIn this context, the study of young children with early brain lesions such as perinatal arterial ischemic stroke (PAIS) provide a unique opportunity to study brain reorganization and plasticity mechanisms taking place before language development unfolds. PAIS occurs in one in 4000 births  and may Considering the role of perilesional functionally spared regions as opposed to the homologous non-affected contralesional brain areas in the current theories of functional recovery after early stroke, we expected children with perinatal stroke affecting the left AF to be the most impaired in language functions. This pattern of results would confirm that the functional integrity of the left hemisphere is mandatory to achieve normal language development . HoweverSix children with symptomatic PAIS (two girls) over the left hemisphere took part in the present study. These children were part of a larger prospective observational multicenter study about acute symptomatic PAIS. The selection of these children was made based on the minimum age at which the behavioural and neuroimaging evaluations could be done at a reasonable time interval for all of them. All but two children received speech therapy on a weekly basis (L2 and L6). Symptomatic PAIS was defined as the finding of an ischemic lesion by MRI study in the territory of the main cerebral arteries  in an infant presenting with seizures, recurrent apnea or acute neurologic deficit during the first days of life. Infants with (1) clear sign of tissue loss or atrophy in MRI suggestive of an old infarction that occurred before birth; (2) vascular malformation; (3) congenital or chromosomic anomalies; (4) metabolic or infectious diseases; (5) complex heart congenital diseases or infants with extra corporeal membrane oxygenation, were excluded from the study. Specifically, MRI-based diagnostics were performed on anatomic data acquired on a 1.5 T whole-body MRI scanner with a specific neonatal head coil within 7 d after the occurrence of the neurologic symptoms. These MRI data allowed classifying the lesions according to the arterial territory involved . The classification of each infarct was obtained by two independent neurologists blind to the clinical data. Discrepancies in the classification of the PAIS were discussed and solved by consensus at joint revaluation among three observers: AGA and two neurologists blind to the clinical data. Motor impairment was considered when infants had clear clinical signs of monoplegia/hemiplegia (GMFCS at least I and/or BFMF at I level). Infants with minor abnormalities such as precocious handedness, mild abnormalities of tone or reflexes that did not interfere with functions were not considered to have a motor impairment. Importantly, while all children presented with seizures during the three first days following birth, no children suffered from epilepsy at the time of the MRI scanBrain MRI was also acquired at 3.8 years (SD = 0.26) to control for the residual lesion and to obtain the functional and structural data reported here. These MRI data demonstrated that all children had infarctions of the MCA affecting several brain regions ; Fig. 1.t(13) = 1.02; p = 0.32. No difference in gender was found . In particular, data used in the preparation of this article were obtained from the Pediatric MRI Data Repository created by the NIH MRI Study of Normal Brain Development . This is a multi-site, longitudinal study of typically developing children, from ages newborn through young adulthood, conducted by the Brain Development Cooperative Group and supported by the National Institute of Child Health and Human Development, the National Institute on Drug Abuse, the National Institute of Mental Health, and the National Institute of Neurologic Disorders and Stroke . A listing of the participating sites and a complete listing of the study investigators can be found at https://www.bic.mni.mcgill.ca/nihpd_info/info2/participating_centers.html. This manuscript reflects the views of the authors and may not reflect the opinions or views of the NIH.In addition, we used a group of nine healthy children  from an MRI pediatric repository to serve as a control for the structural connectivity analyses. The control group and the patients were matched in age  model. Remaining motion effects were minimized by also including the estimated movement parameters in the model. A language > rest and control > rest contrast was calculated. These two contrasts were entered into a second-level paired samples model in which the language > control contrast was calculated for the left hemispheric damage group. Only clusters surviving an uncorrected threshold of To precisely locate the areas affected by the lesion in each patient, we used the four-year-old adapted LONI LPBA40 brain atlas included in the Neurodevelopmental MRI Database  and the www.fmrib.ox.ac.uk/fsl/; Diffusion data processing started by correcting for eddy current distortions and head motion using FMRIB’s Diffusion Toolbox (FDT), which is part of the FMRIB Software Library .For the control group, we directly used the tensors provided by the NIH Pediatric MRI Data Repository .For both patient and control data, whole-brain tractography was performed using Diffusion Toolkit 0.6.2.210 and the interpolated streamlines algorithm. Tractography was started only in voxels with an fractional anisotropy (FA) value >0.2 and was stopped when the angle between two consecutive steps was larger than 35°. Deterministic tracking was performed by means of a two region-of-interest (ROI) approach using the TrackVis software  we decided to use manual deterministic tractography to dissect the tracts of interest, as it allowed us to draw specific ROIs adapted to each individual. In other words, for each individual and tract we drawn in native space-specific ROIs that took into account the neuroanatomy of each participant.in vivo dissections of the IFOF, ILF, and UF. These dissections were performed for both hemispheres. For each dataset, we placed three spherical ROIs , which for the comparison at hand, reflect how likely data are different .Given the location of the patients’ lesions, we analyzed the volume of the AF. The volume was chosen as recent investigations revealed that this WM parameter is sensitive to individual differences  and thatTo explore the link between the volume of the AF and productive aspects of language, we performed four non-parametric Spearman’s correlations between the volume of the complete AF and (1) the two measures of phonological development  and (2) the two measures of expressive language complexity (MLU and L-max). To correct for multiple comparisons, the false discovery rate (FDR) was controlled at δ = 0.05 where multiple tests are performed .The rs-fMRI data were analyzed following the rationale of the tractography analyses. The already preprocessed rs-fMRI data were analyzed using the functional connectivity (CONN) toolbox v17f . After pThe scores obtained in the Peabody vocabulary test  yielded an estimate of verbal IQ which fells within normal limits with all the children having normal verbal IQ A.The scores obtained from selected subtests of the NEPSY-II were first analyzed separately for each subtest. Composite scores corresponding to four of the specific cognitive domains of the NEPSY-II  were also computed by averaging the scalar scores obtained in the target subtests from each domain. As a group, the results showed that the mean scalar scores fell within the normal range  except for phonological processing, narrative memory, block construction, design copying and visuomotor precision subtests showing mean scores slightly below the expected values . When cot test which is specifically designed to compare a patient to a small sample of control participants . This patient presented a particularly poor level of performance in the measure of phonological proximity .Two measures, phonological complexity  and phonological whole-word proximity (proximity score) were obtained. We first compared the individual performance to an age-matched control group using the modified icipants . At the p < 0.001, modified t test, one-tailed; To explore productive language with a specific focus on syntactic complexity, we evaluated the children expressive language complexity by using the MLU in words and the mean length of the five longest utterances (max-L). At the individual level, L1 presented a particularly poor performance in both MLU and max-L scores . A control condition, consisting of an acoustically-matched set of music-like stimuli, was also presented ; the goal of this contrast was to elicit activity related more specifically to linguistic features of the stimuli , rather than prosodic or more low-level auditory cues (such as duration or loudness) which were similar for the two stimulus types. The language versus the acoustic control condition contrast yielded significant (but uncorrected) activity in the right middle temporal gyrus and in the right IFG . We did not observe any substantial damage to the ventral WM pathways  in either hemisphere . Importantly, when comparing the volume of the left and of the right AF between patients and controls, we observed significantly reduced volume of the left AF in patients  and a larger volume of the right AF  in patients as compared to controls. Moreover, to rule out possible group-specific differences due to the different scanning parameters and procedures used between groups, we also compared the laterality indexes of several control tracts also related to language. We found no differences between the laterality indexes of patients and controls for the ILF , IFOF , or UF , which further proves that our results were specific to the AF.Deterministic dissections in the control group revealed that the three segments of the left AF were always present. By contrast, while the anterior and posterior segments of the right AF were always present, we were not able to reconstruct the long segment of the AF in three control children. Crucially, when comparing the laterality index for the volume of the complete AF in patients and controls we found that patients presented a significantly more right-lateralized AF than controls (10), which for the comparison at hand, reflect how likely data are correlated .Given that the dorsal pathway was the most affected in patients , we computed the laterality indices for both dorsal structural and functional data . Due to the limited number of patients, confirmatory Bayesian statistical analyses were computed for all the brain-behavior correlations with the software JASP using default priors and the Bayesian correlation module  between productive aspects of language (as measured by the max-L) and the lateralization index for the volume of the complete AF  as measured by the MLU in spontaneous speech; Following the tractography brain-behavior results, the rs-fMRI analyses showed that the laterality values for the intrinsic connectivity strength between the STG and IFG were positively associated with productive aspects of language  showed that half of the children presented a limited syntactical development as compared to controls. The individual results from the NEPSY-II language subtests showed that most of the children were below normative scores except for the speeded naming subtest. Besides this, most of them had below normative scores in the visuospatial processing subtests. The latter result is in line with two studies reporting impaired visuospatial processing induced by left lesions ,b. TakenN, the presence of anesthesia, the fMRI data were not corrected for multiple comparisons), our results may suggest that both the processing of acoustical features of the voice signal, as well as high-order syntactic processing, were taking place in our group of children.The fMRI results, although not corrected for multiple comparisons, revealed two clusters of activation over the contralesional hemisphere only, one in the right middle temporal gyrus and the other in the right IFG. Prosodic and voice processing have been recently shown to involve a dual processing stream organization with both a dorsal and a ventral pathway connecting the right posterior STG to the right IFG and premotor cortex . Here, wCritically, both rs-fMRI and especially DW-MRI data provided converging evidence showing that the right hemisphere can take over language functions. Successful recovery after early stroke can be associated with both intra-hemispheric perilesional and interhemispheric contralesional plasticity mechanisms . HoweverThe present findings provide important results allowing the refinement of a recent model describing the emergence of increasingly complex linguistic functions through development . BuildinThe present study presents some limitations. The sample size is small, which is an intrinsic and recurrent problem in studying rare neonatal conditions. This limitation is particularly evident for the fMRI results which were not corrected for multiple comparisons. In addition, the fMRI task used here is novel in this type of population and results from a control group of healthy children and/or a group of adults without sedation is needed to further interpret our fMRI data in terms of functional reorganization. The presence of degeneration or necrosis may alter the microstructure of perilesional tissue, leading to problems in the estimation of fiber orientations, especially in areas with presence of crossing fibers, which can, in turn, induce artefacts in track reconstructions . The useIn summary, we report the first 3D reconstructions of the dorsal and ventral language pathways together with fine-grained assessments of cognitive and language functions in a homogeneous group of four-year-old children who had a left PAIS. We provide evidence for an association between the structural and functional  brain reorganization patterns toward the right hemisphere and language production in pre-school children with congenital lesions. We speculate that interhemispheric plasticity through structural and functional hyperconnectivity mechanisms might be crucial for positive outcomes following early lesions.


Single-limb stance instability is a major risk factor for falls in older adults. Thus, improvement of stance stability could play an important role in fall prevention. This study aimed to determine whether high-frequency proprioceptive training (HPT) could significantly improve single stance stability (SSS) in older adults, by increasing proprioceptive control and optimizing the contribution of vision. Sixty-one subjects  aged 65-85 years were investigated. The subjects were randomly assigned to three intervention groups, i.e., HPT, treadmill, and no intervention, stratifying by gender and proprioceptive control at baseline. Stability tests and HPT, consisting of 12 sessions (6 weeks), were performed with computerized postural stations. Pre-post analysis showed that HPT significantly improved SSS by increasing proprioceptive control (p<0.001) and postural control (p<0.01). The treadmill and no intervention groups did not show any significant change. The results showed that different levels of proprioceptive control may activate, inhibit, or minimize the stabilizing intervention of vision. Given that HPT significantly reduced ankle sprains and low back pain in professional athletes (previous study), we discuss the hypothesis that the risk of falls in older adults and the risk of recurrent injuries in athletes would have a common origin: lack of proprioceptive control consequent to reduced interaction with uneven ground. The findings suggest that HPT may be a powerful activator of refined proprioceptive control, which allows increased SSS, safer interaction with the ground, and mitigation of other risk factors. In developed countries, falls are the leading cause of injury in adults over the age of 65 years . The ris Procedures section and was comprehensively explained in a previous article [This study recruited male and female residents in Turin  aged 65–85 years between March 2013 and February 2014 using flyers and posters of invitation in the clinic of general practitioners of the Local Health Unit. Subjects were screened via a phone interview based on the following inclusion criteria: subjects should be able to walk for at least 6 m without an assistive device, could perform the tests in this study, and had not performed any proprioceptive or balance training in 2 years prior to the study. Before the tests, a medical history questionnaire was administered to obtain data on the subject's health status. Subjects with cognitive deficits or health problems were excluded only if the condition could compromise their collaborative capacity or is associated with potential rapid impairment. Sixty-one older adults  were included in the study. Each gender group was divided into two strata according to the level of proprioceptive control. The stability index (SI) in eyes closed (EC) condition was the marker of proprioceptive control. The SI is a score (0-100 %) that takes into account instability and precautionary strategy (hand support). The SI is described in the article . In our  article , it was  article  and was This study used the method of Riva et al. and the methods description partly reproduces their wording , 21.Stability tests and HPT were performed using the Delos Postural Proprioceptive System  . Each stData from the postural reader and the rocking board are a stream of acceleration samples obtained by converting the sensor outputs into the digital domain; at a rate of 100 Hz. Rocking error indicates the average inclination of the board in relation to the horizontal plane. The equations involved in the management of the data from the devices have been described in two previous studies , 21. MorSingle stance stability was assessed with a static single stance test . The staThe postural reader was metrologically characterized through calibration for comparison with a reference triaxial microelectromechanical system accelerometer used as reference standard. This standard was calibrated at Istituto Nazionale di Ricerca Metrologica, which is the National Metrology Institute (NMI) of Italy, with a procedure that was validated through a comparison with that of other NMIs worldwide. Based on the calibration results, the expanded uncertainty (with a confidence level of 95 %) of the postural reader was 0.18, which was within the operative and calibration ranges .SI is a score (0–100 %) that is based on two components: autonomy and average postural instability . SI is capable of ranking all kinds of performances from the highest  to the lowest  level. High SI values in EC trials correspond to refined proprioceptive control, the expression of effective proprioceptive reflexes that stabilize the subject rapidly before activation of vestibular responses . Lower Sreduced precautionary strategy  when the contribution of vision to stability is limited by an extremely low proprioceptive control level,optimized postural control by activating more effective proprioceptive reflexes (proprioceptive control) and minimizing the contribution of vision to stability.HPT consisted of 12 sessions  and was based on the active management of high-frequency rocking instability (rolling + inclination) of the board . The reaAnkle mobility improvement: the rocking base is used as an inclined plane to experience maximum pronation and supination, plantarflexion, and dorsiflexion (15°) in a static condition Figures .High-frequency instability of the rocking base .Feedback of vertical control.Assignment of specific tasks concerning board control and postural control. The exercises with the rocking base were performed in various orientations of the support surface to affect different ranges of motion of the ankle .Tasks for exploring the ankle range of motion dynamically: the visual information allowed for the assignment of specific tasks, such as maintaining the rocking base at an inclination corresponding to a certain level of pronation or supination, dorsiflexion, or plantarflexion Figures  or passiHyper-frequency instability: more details of the rocking movement were shown by zooming the trace on the display. The greater number of details led the subject to further increase the frequency of correction. The proprioceptive training was based on the following key concepts. The last three proprioceptive training sessions consisted of a sequence of longer trials lasting 40 s, alternating the left and right limbs. The recovery period between repetitions decreased from 15 to 10 s. The actual training time progressively increased from 18 to ≥22 min. The training density  increased from 40 % to ≥50 %.The treadmill group performed 12 sessions (two sessions a week for 6 weeks) of walking on a treadmill. The training speed in each session was calculated by increasing the usual speed of the 6-m test by a correction factor . The purpose was to propose an increasing training speed in each session tailored to the functional level of the subject. All sessions consisted of four walking blocks, with 3-min rest for passive recovery (seated). In each session, all blocks were equal; in each block, the subject started approaching the training speed (1 min), continued maintaining the training speed (3 min), and decreased the speed until completion (1 min). Each session lasted 29 min with 20 min of walking time.The participants were asked to maintain their usual physical activity and walking time.http://www.medcalc.org; 2018).Analysis of variance was used to analyze the differences between group means. When comparing the effect of intervention within every intervention group , the paired t-test was used. The normal distribution was verified with the Shapiro-Wilk test. Analyses were stratified by gender and proprioceptive control (SI in EC condition) at baseline. The values of p were two-tailed, and p≤0.05 was considered statistically significant. All analyses were performed using MedCalc Statistical Software version 18.2.1  are summarized in Twelve sessions of walking on a treadmill at increasing speed in 6 weeks failed to improve the proprioceptive control and postural control (EC and EO stability) in both genders. Similarly, the no-intervention group did not show any change in the parameters, in either men or women, compared to baseline values.HPT could significantly improve, in both genders, single stance stability based on proprioceptive control (EC stability). Improvement in proprioceptive control could also enhance postural control (EO stability) significantly, in most cases decreasing visual dependence or unblocking the stabilizing contribution of vision (see point (2)).Different levels of proprioceptive control could activate different engagement of vision in response to proprioceptive training Figures  and 4. TWomen aged 75–84 years are significantly less stable than men ; this diWalking on a treadmill at an increasing speed failed to significantly improve proprioceptive control and postural control , in both genders. A previous study  that invThe study investigated whether quantifiable HPT could improve single stance stability by increasing proprioceptive control and optimizing the contribution of vision as a compensatory stabilizer. The primary findings of this study are as follows. In developed countries, lack of interaction with uneven ground reduces reflex activation of the stabilizing muscles and minimizes the mechanical solicitations of the weight-bearing structures . Thus, these structures become more fragile and the stabilizing muscles become weaker. Consequently, the single stance phase becomes more unstable mainly because of the weakness of the extrinsic and intrinsic muscles of the foot, which are unable to generate adequate forces to stabilize the weight-bearing leg and the upper part of the body. This is worsened by the structural frailty of the passive structures that are unable to serve as a strong anchorage point. Based on these findings, increasing the duration of walking on flat surfaces, even at a higher speed, is ineffective for increasing proprioceptive control (EC stability) and postural control (EO stability) in single stance.The compensatory role of vision as a postural stabilizer makes the subject only apparently more stable. The necessity of maintaining the eyes anchored to the environment  could exNo specific definition of proprioceptive exercises acting on the unconscious component of proprioception exists . GeneralWe speculated that lack of interaction with uneven ground is the initial determinant in the causal chain leading to lack of proprioceptive control and consequent high risk of falls in older adults. It is interesting to note that the results of the present study are consistent with those found in a previous six-year prospective study concerning injury prevention in a professional basketball team . In thatThe main limitation of this study could be the self-selection bias. People who volunteer to participate in a study tend to be different from the rest of the population , thereby limiting the external validity of the results . NeverthAnother limitation was the sample size. Analysis involving several age classifications and more functional levels is possible with a greater number of subjects.HPT  significantly improved single stance stability in older adults by increasing proprioceptive control and optimizing the contribution of vision as stabilizer. Different levels of proprioceptive control could minimize, inhibit, or activate the involvement of vision as a stabilizer. In cases with progressively lower values of proprioceptive control (SI in EC between 90 % and 30 %), the visual stabilizer tends to increase its compensatory action; in these cases, HPT results in increased proprioceptive control and reduced visual dependence to achieve stability. However, extremely low proprioceptive control (SI in EC ≤30 %) inhibits the compensatory role of vision as a stabilizer; in this case, a moderate increase in proprioceptive control (stability in EC condition) significantly activates VG, improving stability in the EO condition.HPT would emerge as a powerful activator of refined proprioceptive control, which allows increased single stance stability, safer interaction with the ground, and mitigation of other risk factors. The effectiveness of HPT in strengthening the stabilizing muscles is also endorsed by the finding that treadmill walking, i.e., walking on a flat and smooth surface, does not significantly improve proprioceptive control and postural control , in both genders.Older adults should start HPT before the risk of fall becomes evident to maximize the results of HPT . Early HPT allows more intense succeeding HPT sessions with cumulative effects. Our preliminary results with a 10-year follow-up showed that 12–18 consecutive sessions per year  starting between the age of 60 and 75 years could determine a progressive and continuous improvement in stability. As instability takes more than ten years to become evident, an early preventive intervention would increase the results and reduce the cost. Considering that proprioceptive control in single stance could be an important element of safety and mobility independence, further research with long-term follow-ups on the cumulative effects of periodical HPT is suggested.


Portal annular pancreas (PAP) is a rare congenital anatomical abnormality of the pancreas in which the portal vein is encircled by aberrant parenchyma, and special attention is needed for pancreatic resections. This is the first report of central pancreatectomy (CP) in a PAP for metastatic renal cell carcinoma (RCC).A 76-year-old man who had a history of left nephrectomy for renal cancer not otherwise specified 36 years earlier and radical cystectomy for bladder cancer 4 years earlier was incidentally found to have a pancreatic tumor and a liver tumor. The pancreatic tumor was diagnosed as metastasis of clear cell RCC, and the liver tumor was diagnosed as moderately differentiated hepatocellular carcinoma (HCC) on preoperative histological evaluation. Preoperative computed tomography imaging showed a type 3A PAP, in which the main pancreatic duct (MPD) ran ventral to the portal vein , and the aberrant parenchyma was located cranial to the confluence of the portal vein and splenic vein (suprasplenic type). After adhesiotomy and partial liver resection, CP was performed. With intraoperative ultrasound guidance, the aberrant parenchyma of the PAP could be preserved, avoiding additional resection. Thus, two pancreatic transections were performed, creating a single-cut margin that contained the MPD in the distal pancreas. Oncologically safe margins were confirmed by intraoperative pathological diagnosis. The distal pancreas was reconstructed by pancreatojejunostomy in the routine procedures. The pathological diagnosis of the surgical specimens was identical to the preoperative diagnosis. A postoperative pancreatic fistula (POPF) developed from the proximal stump of the head of the pancreas, necessitating no specific treatment other than drainage. The patient showed no signs or symptoms of recurrent RCC or abnormal pancreatic function for 2 years after the operation, although a histologically proven new HCC lesion developed distant from the initial site 8 months after the operation.Precise preoperative evaluation of the tumor features and PAP allowed adequate surgical strategies to be planned. Intraoperative ultrasound was useful to minimize parenchymal resections of the PAP. CP is still a challenging procedure in terms of the development of POPF. Portal annular pancreas (PAP), which is also called circumportal pancreas, is a rare congenital anatomical abnormality of the pancreas. There is continuity between the uncinate process of the pancreas and the body of the pancreas via the aberrant parenchyma, resulting in the portal vein being encircled by pancreatic parenchyma. PAP is usually asymptomatic, but special attention is needed for pancreatic surgery in terms of the location of the main pancreatic duct (MPD) and the way to resect parenchyma to minimize the risk of postoperative pancreatic fistula (POPF). PAP is classified based on the running patterns of the MPD  and the 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). FDG-PET was negative for the pancreatic and liver tumors. To identify tumor features, endoscopic ultrasound-guided fine-needle aspiration (EUS-FUA) for the pancreatic tumor and percutaneous ultrasound-guided biopsy for the liver tumor were performed. Histologically, the pancreatic tumor was diagnosed as metastasis of clear cell RCC, with positive staining for CD10 and vimentin and negative staining for CK7, CK20, alpha-fetoprotein, and neuroendocrine markers on immunohistochemical analysis. The liver tumor was diagnosed as moderately differentiated hepatocellular carcinoma (HCC). Preoperative CT imaging also showed type 3A PAP, in which the MPD ran ventral to the portal vein, and the aberrant parenchyma was located cranial to the confluence of the PV and SPV  36 years earlier and radical cystectomy with creation of a right cutaneous ureterostomy for invasive urothelial carcinoma of the bladder 4 years earlier was incidentally found to have a pancreatic tumor and a liver tumor on regular follow-up computed tomography (CT) after radical surgery for bladder cancer. On dynamic CT, the pancreatic tumor was located in the head of the pancreas, ventral to the portal vein, with a size of 10 mm, and it showed clear, strong enhancement in the arterial phase , SPV, common hepatic artery (CHA), and gastroduodenal artery (GDA) were well mobilized from the head of the pancreas. Then, tunneling of the pancreatic neck over the PV was completed, and the neck and body of the pancreas were well mobilized from the PV and SPV Fig. a. IntraoThe final pathological diagnosis was identical to the preoperative diagnosis. Histologically, the pancreatic metastasis of clear cell RCC that contacted the MPD formed a fibrous capsule and showed capsular invasion Fig. . The proPAP is a rare congenital anatomical abnormality of the pancreas that is usually asymptomatic. Analysis of CT imaging showed a prevalence of 0.8 to 2.5% . In receTo the best of our knowledge, this is the first report of CP in PAP. Intraoperative ultrasound was also useful to determine oncologically safe surgical margins and minimize the parenchymal resection, preserving the aberrant parenchyma of the PAP during CP. The patient did not show any signs or symptoms of abnormal pancreatic function for 2 years after the operation. A single-cut margin containing the MPD in the distal pancreas was created, and no changes in the routine procedures were needed for PJ reconstruction. However, POPF grade B developed from the stapler-closed cephalic stump. Sho et al.  reportedPancreatic metastasis (PMet) from other primary cancers is rare, accounting for about 1–2% of all pancreatic cancers , 20. It Precise preoperative diagnosis of the tumor histology and the PAP enabled sufficient preoperative simulations. CP was successfully performed in type 3A PAP for metastatic RCC, avoiding additional resections of the aberrant parenchyma. Intraoperative ultrasound was useful not only to identify the MPD, but also to minimize parenchymal resection, maintaining oncological safety. CP is still a challenging procedure in terms of POPF.