Cervical artery dissection (CAD) and stroke are serious harms that are sometimes associated with cervical spinal manipulation therapy (cSMT). Because of the relative rarity of these adverse events, studying them prospectively is challenging. As a result, systematic review of reports describing these events offers an important opportunity to better understand the relation between adverse events and cSMT. Of note, the quality of the case report literature in this area has not yet been assessed.1) To systematically collect and synthesize available reports of CAD that have been associated with cSMT in the literature and 2) assess the quality of these reports.A systematic review of the literature was conducted using several databases. All clinical study designs involving CADs associated with cSMT were eligible for inclusion. Included studies were screened by two independent reviewers for the presence/absence of 11 factors considered to be important in understanding the relation between CAD and cSMT.Overall, 43 articles reported 901 cases of CAD and 707 incidents of stroke reported to be associated with cSMT. The most common type of stroke reported was ischemic stroke (92%). Time-to-onset of symptoms was reported most frequently (95%). No single case included all 11 factors.This study has demonstrated that the literature infrequently reports useful data toward understanding the association between cSMT, CADs and stroke. Improving the quality, completeness, and consistency of reporting adverse events may improve our understanding of this important relation. In the area of harms reporting, one topic that has received significant attention is cervical spinal manipulation therapy (cSMT), an intervention most often administered by chiropractors While the reporting of rare events occurs frequently in larger studies ), the event is often not reported with sufficient details. Furthermore, systematic reviews where harms have been reported often exclude non-RCTs To systematically collect and synthesize reports of CAD associated with cSMT and assess reporting quality.The following electronic databases were searched between January 2001 to January 2011: MEDLINE, CINAHL, ALT HealthWatch, AMED, and EMBASE. The search strategy for these databases including limits used and Boolean operators are presented in Study design: All clinical study designs.Population: Adults and children of any gender.Intervention: cSMT  Comparison: Not relevant.Outcomes: Cervical arterial dissections  or stroke  Language: Articles in either English or French were considered for inclusion.Titles and abstracts of records obtained from the search were screened by two independent reviewers (SW and MW). The full texts of potentially relevant studies were then screened independently by the same two reviewers using the inclusion criteria described below. Where reviewers disagreed, consensus was resolved by discussion.th factor regarding the stroke type was collected and tabulated. Disagreements regarding the presence or absence of any of the 11 factors were resolved by consensus. The reporting frequency of each factor was then calculated.To evaluate the quality of cases that reported an association between cSMT and CAD, 21 factors were derived from Bradford-Hill criteria  which arWe could not identify any standard guidance regarding the conduct of meta-analysis from case reports and case studies and therefore data are summarized in text. All relevant information for the CAD and stroke cases were collected, tabulated and expressed as a percentage.The flow of studies through this review can be found in the Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) diagram The diagnosis of CAD was reported in all articles included in this manuscript. Approximately 70% of the cases reported described dissection of the vertebral artery and carotid artery. In the reported cases, a subset of 852 cases confirmed the diagnosis using either angiography (34%), magnetic resonance imaging (with or without angiography) (34%), and computed tomography (9%). The remaining 23% of the cases were confirmed using other methods such as Doppler ultrasonography and duplex sonography. In all imaging studies, criteria such as the appearance of stenotic vessels, flow abnormalities, or the presence of an intimal flap were used to confirm the CAD diagnosis, The largest study performed by Rothwell et al did not provide any information regarding how the diagnosis of CAD was made Of the 901 cases of CAD associated with cSMT, 707 (85%) cases reported stroke type; however, the anatomical location of the infarct was only reported in 32 out of the 706 ischemic infarcts. Strokes reported post-cSMT were all ischemic, with one hemorrhagic transformation in the parietal-occipital region Of the 43 articles that met inclusion criteria for this study, there were 24 case reports th criteria regarding cSMT-specific factors . Only one paper described the cSMT procedure itself or the anatomic location of cSMT application Papers were reviewed for an 11This study assessed the quality of investigations that reported cSMT associated with CAD by determining the frequency with which specific quality factors were described. Because it is recommended that case reports should be included in systematic reviews of relatively rare harms, the quality of these reports is of critical importance in knowledge synthesis. Overall, the quality of case reports examined in this study was low in that they infrequently contained more than 5 of the 11 relevant factors.Certainly, previous papers have also identified limitations of case reports within the cSMT/CAD literature. A previous review provided limited data regarding subject demographics, time-to-onset of symptoms, and the profession of the cSMT provider In studying the association between cSMT and CAD, it is important to understand the events preceding the application of cSMT and the onset of CAD. Unfortunately, the results from this study demonstrate a general deficiency in reporting events preceding cSMT or CAD other than that the patient presented to the emergency clinic following cSMT. Clearly, case reports discussing the development of a stroke should endevour to include an etiological work-up so that an alternative cause of the patient’s presentation might also be elucidated. For example, spinal manipulation is a therapeutic modality that is used to treat head and neck pain Identifying the stroke type when reporting cSMT associated with CADs would be useful for those practitioners who frequently examine patients presenting to the emergency room (or clinic) with stroke-like symptoms following a therapeutic intervention. Understanding of the typical stroke presentation might help with rapid identification of injury location and assist in the determination of a management protocol. Our study demonstrates that while stroke type was reported often, the anatomical location of the stroke was not. Given that stroke symptoms are specific to the area affected by the lesion, further understanding of the management of patients with strokes thought to be associated with cSMT might occur with increased reporting of injury location rather than simply stating the type of stroke.The lack of reporting regarding cSMT-specific factors was similar to the under-reporting of other factors. This is an important omission as there is an inherent variability of cSMT techniques used by manual therapists. While some investigators have examined the mechanical forces associated with instrument-assisted spinal manipulation www.equator-network.org). Currently, at least two sets of guidelines have been identified which if used, may improve the quality of case report literature Our study has demonstrated that there are deficiencies in reporting key factors associated with CAD and cSMT. While the temporality and location of the injury were reported consistently, additional efforts are needed to improve harms reporting so that clinicians are provided with accurate information about various therapies and their potential sequelae. One approach to improved reporting has been suggested by the EQUATOR  network comprised of researchers working towards improved quality of the published literature. The network hosts an up-to-date library of reporting guidelines for health research on their website Click here for additional data file.


There is a debate regarding the choice of operative intervention in humeral shaft fractures that require surgical intervention. The choices for operative interventions include intramedullary nailing (IMN) and dynamic compression plate (DCP). This meta-analysis was performed to compare fracture union, functional outcomes, and complication rates in patients treated with IMN or DCP for humeral shaft fractures and to develop GRADE -based recommendations for using the procedures to treat humeral shaft fractures. A systematic search of all the studies published through December 2012 was conducted using the Medline, Embase, Sciencedirect, OVID and Cochrane Central databases. The randomized controlled trials (RCTs) and quasi-RCTs that compared IMN with DCP in treating adult patients with humeral shaft fractures and provided data regarding the safety and clinical effects were identified. The demographic characteristics, adverse events and clinical outcomes were manually extracted from all of the selected studies. Ten studies that included a total of 448 patients met the inclusion criteria. The results of a meta-analysis indicated that both IMN and DCP can achieve similar fracture union with a similar incidence of radial nerve injury and infection. IMN was associated with an increased risk of shoulder impingement, more restriction of shoulder movement, an increased risk of intraoperative fracture comminution, a higher incidence of implant failure, and an increased risk of re-operation. The overall GRADE system evidence quality was very low, which reduces our confidence in the recommendations of this system. DCP may be superior to IMN in the treatment of humeral shaft fractures. Because of the low quality evidence currently available, high-quality RCTs are required. Fractures of the humeral shaft are commonly encountered in orthopedic clinics, and these fractures make up 1.31 to 3% of all fractures Surgical treatment is generally indicated in patients in whom there is a failure to maintain stable alignment and reduction at the fracture site and in the patients with severe segmental fractures, open fractures, or fractures associated with bilateral fractures, forearm fractures on the same side, poly-trauma, progressive neurological deficits, vascular injury or floating shoulder or elbow Several randomized controlled trials (RCTs) or quasi-RCTs have been conducted to compare IMN with DCP in treating humeral shaft fractures. There is controversy over which of the two procedures leads to superior results and better clinical outcomes. There is no consensus as to whether IMN or DCP is the optimal treatment. The purpose of this meta-analysis is to evaluate the evidence from the RCT and quasi-RCT studies that compared the safety and efficacy of IMN and DCP for treating patients with humeral shaft fractures and to develop GRADE -based recommendations for using the procedures to treat humeral shaft fractures To assemble all of the relevant published studies, PRISMA compliant searches of MEDLINE, EMBASE, ScienceDirect, OVID, the Cochrane CENTRAL databases and Google scholar were performed for all the peer-reviewed studies published through February 2013 that compared KP to VP for treating OVCF. The following search terms were used to maximize the search specificity and sensitivity: humeral fractures, fracture fixation, intramedullary nails, and bone plates. Broad MeSH terms and Boolean operators were selected for each database search. Secondary investigations into the unpublished literature were performed by searching the WHO International Clinical Trials Registry database, Current Controlled Trials, European Federation of National Associations of Orthopaedics and Traumatology and British Orthopaedic Association Annual Congress, and the ISTP database.The complete articles found by the above search methodology were retrieved and assessed for the inclusion/exclusion criteria outlined in Two reviewers (MJX and XD) independently screened the titles and abstracts for the eligibility criteria. The full text of the studies that potentially met the inclusion criteria were read, and the literature was reviewed to determine the final inclusion. We resolved disagreements by reaching a consensus through discussion.Two of the authors (MJX and XD) independently extracted the data from each full-text report using a standard data extraction form. The data extracted from studies included the title, authors, year of publication, study design, sample size, population, age, gender, type of interventions, surgical procedures, duration of follow-up, and outcome parameters. The corresponding authors of the included studies were contacted to obtain any required information that was missing. The extracted data were verified by MXL.The clinical outcomes included: fracture union, iatrogenic radial nerve injury, intraoperative fracture comminution, infection, shoulder impingement, restriction of shoulder range of movement, implant failure, American Shoulder and Elbow Surgeons (ASES) score.According to Cochrane Handbook for Systematic Reviews of Interventions 5.0, the risk of bias of the included studies was assessed by two authors (MJX and XD) independently. Disagreements were resolved by discussion. A third author (MXL) was the adjudicator when no consensus was achieved. We applied the “assessing the risk of bias” table, which include the following key domains: adequate sequence generation, allocation of concealment, blinding, incomplete outcome data, free of selective reporting and free of other bias.We performed all of the meta-analyses with the Review Manager software . For continuous outcomes, such as the ASES score, the means and standard deviations were pooled to a weighted mean difference (WMD) and a 95% confidence interval (CI). The risk ratios (RRs) and 95% confidence intervals (CIs) were used to evaluate the dichotomous outcomes, such as the incidence of bone cement leakage or adjacent fractures. The inverse variance and Mantel-Haenszel techniques were used to combine the separate statistics. A P-value <0.05 was considered statistically significant. The statistical heterogeneity was assessed using Q statistics. A fixed-effects (inverse variance) model was used when the effects were assumed to be homogenous (P>0.05). P<0.05 implied statistical heterogeneity, and a random effects model was used in those circumstances.Publication bias was assessed visually using a funnel plot and statistically using Begg funnel plots and Egger's bias test using STATA 12.0 software , which measures the degree of funnel plot asymmetry The evidence grade was determined using the guidelines of the GRADE  working group A total of 319 titles and abstracts were preliminarily reviewed, and 10 studies eventually satisfied the eligibility criteria . These sAmong the 10 included studies, the methods of randomization of 8 RCTsThe demographic characteristics of the studies included are summarized in In all the studies providing comparisons of fracture union between IMN and DCP, the pooled RR was −0.96 (95% CI: 0.90–1.02). There was no significant difference between the groups . Only 3 The publication bias test was performed for the overall populations by the incidence of radial nerve injury. No significant publication bias was shown for the overall populations by the Begg rank correlation method (P = 0.107) and Egger weighted regression method (P = 0.992).Nine outcomes in this meta-analysis were evaluated using the GRADE system. The following 4 outcomes were important: fracture union, ASES score, radial nerve injury, and intraoperative fracture comminution. The evidence quality for each outcome was very low . We agreFractures of the humeral shaft are common and result in a significant burden to society Although Kurup et al.The methodological quality assessment identified a number of limitations to the current evidence base. (1) The majority of the RCTs had insufficient information on the randomization methods. Only three included studies used sealed envelopes for allocation concealment. The patients of the two quasi-RCTs were randomly allocated by an incorrect randomization method, namely by odd and even hospital numbers. These methods permitted selection and allocation bias. None of the included studies reported blinding of the surgeons, participants or assessors, allowing for assessor and expectation bias and the potential for type II statistical errors regarding these outcomes. The efficacy of the statistics could be improved in the future by including more RCTs. The studies with a high risk of bias included in this meta-analysis would overestimate the treatment effects. (2) Although RCTs or quasi-RCTs were performed, the relatively small number of participants restricted the statistical power. (3) The long-term follow-up results may change the current conclusions. (4) Clinical heterogeneity may be caused by the preexisting conditions of the patients, various indications for surgeries, the experience level of the orthopedic surgeons, fracture type, medical commodities, smoking and the age of fractures (acute or nonrecent fractures). The above confounding factors might have an impact on the present outcomes. (5) Meta-analyses are subject to bias and provide inappropriate estimates for the effect of treatment when compared to successive large RCTs All of the included studies conducted comparisons between IMN and DCP in treating humeral shaft fractures, but no study provided conclusive evidence in favor of either surgical approach. The pooled data for fracture unions did not result in significant findings favoring one of the two implants. IMN provides acceptable micromotion at the fracture site, which promotes fracture healing, but the effects of reaming may exert an influence on the blood supplying at the fracture site. DCP could offer an accurate reduction, which may promote fracture healing. IMN could achieve a comparable fracture union rate to DCP fixation. The timing of delayed union or nonunion varied in the studies of the present meta-analysis, which may increase the risk of bias of the pooled results. A unified timing of fracture union is required in future studies.Regarding the ASES score, though there was a trend favoring DCP, the present meta-analysis found no statistically significant differences between the two interventions. There was not enough evidence to determine the ASES score between the two groups because only three studies were included in the present meta-analysis. The statistical power may be lower because of the small sample size.In respect to iatrogenic radial nerve injury, the difference between the two groups was not statistically significant. The open reduction and internal fixation of humeral shaft fractures can be performed through a variety of approaches. The anterolateral approach is useful for the exposure of fractures involving the proximal and middle thirds of the humeral shaft. The benefits of this approach include its extensile nature and avoidance of the radial nerve. A posterior approach may be better suited for fractures extending between the olecranon fossa and the distal middle-third of the humerus. This approach accommodates very distal plating of the humerus along the posterolateral column, where additional fixation into the posterior capitellum is critical for the stability of the distal segment. The anteromedial approach may be of benefit because of the direct access it provides to the radial nerve. The selection of a surgical approach by the surgeons is determined by his or her experience and the location of fractures. In both approaches, the radial nerve must be dissected and identified to avoid iatrogenic injury from either cutting it during exposure or plating over it during fracture fixation. A detailed description of the approach in each patient cannot be obtained from the individual studies. The incidence of radial nerve injury by DCP fixation was affected by the above confounding factors. In the IMN procedure, the iatrogenic stretching of the radial nerve during ante grade nailing with the use of a mallet might account for the iatrogenic radial nerve injury. IMN was comparable to DCP in iatrogenic radial nerve palsies, but the fact that IMN has the advantage of preventing exposure and soft-tissue stripping might make this method preferable over DCP fixation for surgeons.Regarding iatrogenic fracture comminution, the pooled results showed that DCP was superior to IMN. For the distal third of the humeral shaft, retrograde nailing is indicated only in patients with a wide medullary canal. It is critical to create a sufficiently large entry portal and to perform careful introduction to avoid supracondylar or other additional fractures.Regarding the risk of infection, the impairment of the blood supply and wide exposure may increase the risk of infection with DCP, especially in the middle and distal parts of the humeral shaft. Minimally invasive plating osteosynthesis, as a minimal invasive and limited dissection technique, has recently been used to protect the blood supply at the fracture site The meta-analysis showed that DCP is superior to IMN regarding shoulder impingement and restriction of the shoulder range of motion. In patients with humeral shaft fracture who underwent IMN, shoulder impingement was caused by a prominent nail, and the restriction of the shoulder range of motion was caused by scar tissue and/or damage to the rotator cuff in its critical zone of hypovascularity creating chronic tendon tearing. Several studies have investigated different approaches to improve the outcomes by avoiding the avascular zone of the rotator cuff. These studies reported that careful repair of the tendon after nail insertion may provide better outcomes and less morbidity In the respect to implant failure and the re-operation rates, the pooled results showed that DCP was superior to IMN. In the DCP groups, the rotation force and shear force were unable to pass through the fracture site, which led to higher stress concentrations on the implant. In the IMN groups, implant failure usually occurred due to breakage of the nail at the site of the distal or proximal locking screw. This complication was frequently associated with patient rehabilitation after fixation. The plans and methods for postoperative rehabilitation should be formulated by the radiographic evaluation of healing, which may lower the risk of implant failure. The re-operation rate was an overall outcome because the presence of complications such as infection, implant failure, restriction of joint motion, nonunion, or delay union usually necessitates a re-operation such as implant exchange or implant removal to achieve refixation or functional recovery. The indications for re-operation for certain complications remained inconclusive In the GRADE system of rating the quality of evidence, each RCT began as high quality evidence but was rated down by five categories of limitations. The method of random sequence generation was not stated in most of trials, and insufficient details were provided to confirm adequate concealment of allocation. Variation in the timing of follow-up was a potential source of bias, and an intention-to-treat analysis was not confirmed in any of the trials. There were no independent or blinded assessments of the outcome. We consider that the above factors could significantly influence the stability of the outcomes. The above factors of methodological quality accounted for the downgraded evidence quality. The overall strength of the references was very low. The overall very low evidence quality indicates that the operations should be conducted according to the characteristics of the individual patients in clinical practice. High-quality clinical trials are required to compare the advantages or disadvantages of IMN and DCP in the future. To some extent, the present study is meaningful for both clinical treatment and fundament research.The present study showed that both IMN and DCP can achieve similar fracture union rates with similar incidences of radial nerve injury and infection. IMN was associated with increased risk of shoulder impingement, a higher restriction of shoulder movement, an increased risk of intraoperative fracture comminution, a higher incidence of implant failure, and an increased risk of re-operation. DCP may be superior to IMN in the treatment of humeral shaft fractures, but the overall quality of the evidence is very low according to the GRADE system, which may reduce our confidence in the recommendations for the use of DCP. Because of the very low quality of evidence, sufficiently sized and methodologically sound RCTs are needed to assess the safety and efficiency of the IMN and DCP procedures in treating humeral shaft fractures.Checklist S1Preferred reporting items for systematic reviews and meta-analysis (PRISMA) 2009 Checklist.(DOC)Click here for additional data file.


Salmo trutta) in the Duero basin, an Atlantic river basin in the Iberian Peninsula, where a spatial segregation of two divergent lineages was previously reported, based on isozyme, microsatellite and mtDNA data. In these studies, two divergent pure regions (Pisuerga and Lower-course) and several hybrid populations between them were identified. Morphological variation was evaluated in 11 populations representative of the genetic differentiation previously observed in the Duero basin, using multivariate analysis on 12 morphometric and 4 meristic traits. A large differentiation between populations was observed (interpopulation component of variance: 41.8%), similar to that previously detected with allozymes and microsatellites. Morphometric differentiation was also reflected by the high classification success of pure and hybrid individuals to their respective populations, using multivariate discriminant functions . All multivariate and clustering analyses performed demonstrated a strong differentiation between the pure regions. The hybrid populations, though showing large differentiation among them, evidenced an intermediate position between the pure samples. Head and body shape traits were the most discriminant among the morphometric characters, while pectoral rays and gillrakers were the most discriminant among the meristic traits. These results confirmed the high divergence of the brown trout from the Duero basin and suggest some traits on which selection could be acting to explain the spatial segregation observed.The aim of this study was to analyze the morphological variation of brown trout ( Salmo trutta) is one of the most well researched European fish. It is also one of the vertebrate species with highest genetic subdivision . Twelve morphometric and four meristic characters were measured on fresh specimens shortly after death. The morphometric characters included caudal peduncle, body and head depth, eye diameter, distance between pectoral and pelvic fin, distance between pelvic and anal fin, maximum body width at the level of the dorsal fin origin, maximum gape width at the level of the posterior end of the maxilla, head and jaw lengths, and preorbital and postorbital distances. All measurements were taken to the nearest 0.01 mm, using a digital calliper. Before analysis, all morphometric measures were standardized according to the following expression:Yij' is the adjusted value of character j for individual i, Yij is the original value, bj the allometric coefficient (the slope of the relationship between log Xi and log Yij), Xi the standard length of individual i, and X a rounded-up mean of standard length from all samples (150 mm). The standard length is the length of fish measured from the tip of the snout to the posterior end of the midlateral portion of the hypural plate. Standardization of all morphometric measurements minimizes variability resulting from allometric growth and differences in mean size of individuals among populations  of variance-covariance matrix on morphometric and meristic variables was firstly used to reveal patterns of geographic variation between samples. For this analysis, the populations from Pisuerga (P1 and P2) and Lower-course (AG1 and AG2) were pooled, to obtain a single reference from each pure region. Components with eigenvalues > 1 were selected and scores of the loading matrix after varimax rotation evaluated. Centroid scores derived from the most informative principal components in each data set were labelled and plotted against.Multiple discriminant analysis (MDA) was applied to the pure regions (Pisuerga and Lower-course) to get a discriminant function based on morphometric measurements. A classification matrix was constructed by assigning specimens to populations, on the basis of the linear combination of variables from the discriminant function. The jackknife method was used because it partially removes the bias inherent in classifying cases into groups that were used to define them . Then, this discriminant formula was used to compute canonical scores based on measurements from the hybrid samples, for comparing the values of pure regions with those of the hybrid populations. Diagram plots were used to display discriminant scores of each sample with respect to pure regions.In addition, to assess the similarity between the hybrid populations, a second discriminant analysis was performed, using morphometric characters only from these populations. A classification matrix (jackknife method) was constructed by assigning specimens to populations, based on the linear combination of variables from each discriminant function. These discriminant functions were employed again to compute canonical scores, based on measurements from the two pure regions. A cluster analysis (Ward's method using Euclidean distance) was used to show the degree of similarity among the hybrid populations according to discriminant scores, using the group of centroids for each discriminant function as variables. Centroid groups from Lower-course and Pisuerga regions were added to the cluster analysis, to show their position with respect to other groups.The same procedure described above was also applied to the meristic traits. However, the differentiation between pure regions was not so clear, and multivariate discriminant analysis was then applied to all populations together. As in the other cases, a classification matrix (jackknife method) was constructed and a cluster analysis (Ward's method using Euclidean distance) was used to show the degree of similarity among the different groups.Analysis of the variance showed a highly significant divergence among the populations from the Duero basin . The relative component of variance was very high, ranging between 25.3 for pelvic rays and 60.7 for body depth . The meaa priori grouping of the data, this assumption-free ordination of data justified the starting point hypothesis in the MDA analysis, to say that the pure samples constituted the extremes of the morphological range in the Duero basin.PCA on morphometric characters extracted three factors explaining 64.3% of the variance in the data . The first component was related with several measures of the head , whereas the second one was associated with traits related to body shape  . These tThe MDA using morphometric traits provided an almost complete segregation between the Lower-course and the Pisuerga samples, showing a clear-cut difference between the discriminant scores . The most salient traits to discriminate pure samples were jaw length, head length and head depth . ApplicaWhen the discriminant analysis was applied to the morphometric variables in the seven hybrid populations, six statistically significant discriminant functions  were found . The firFour discriminant functions were obtained from the meristic characters, three of which were statistically significant  and microsatellites . This differentiation was high across all population pairs and characters, as evidenced by the post-hoc tests performed. However, three characters  showed a higher contribution to the global differentiation observed. This was in accordance with the high discrimination power of these characters evidenced by multivariate analyses. Likewise, the high percentages of individuals correctly classified to their respective samples after the application of discriminant analyses reflected the high morphological differentiation among populations in the Duero basin, as reported using the microsatellite markers (e.g. differences in temperature and oxygen content during early ontogeny) may contribute to the large variation observed.The large and significant differentiation among populations observed for all morphological traits studied in brown trout from the Duero basin is in accordance with the high genetic diversity detected previously with isozymes, mtDNA and microsatellites  analyses and clustering methods consistently showed the highest morphological divergence between the pure regions, Pisuerga and Lower-course, as previously reported with molecular markers  beyond te.g. length of jaw, mouth position or eye diameter) have demonstrated to be related to prey-detecting and handing in different species of fish (The results obtained demonstrate that the genetic differentiation reported in the Duero basin is associated to morphological variation. Morphological differences in brown trout have sometimes been associated to environmental plasticity , but in  of fish . In our  of fish . All the of fish .The morphological variation found in our study is concordant with previous genetic data (


Given that the blood-testis barrier is more permeable than the blood–brain barrier, the use of semen to detect rare parasitic antigens/infections of the CNS in males is hypothesized. Acanthamoeba and Balamuthia mandrillaris and primary amoebic meningoencephalitis due to Naegleria fowleri has made accurate diagnosis challenging [Infections of the central nervous system (CNS) can progress rapidly and cause substantial damage or even death if they are not diagnosed promptly and treated aggressively. Given the involvement of the CNS, it is typical to use cerebrospinal fluid for the identification of infectious agents/antigens, and the host factors to suspected disease. In general, pathogens colonize mucosal surfaces, followed by invasion of the intravascular space leading to haematogenous spread and entry into the CNS at the sites of the blood–brain barrier (BBB) or blood-cerebrospinal fluid (CSF) barrier at the choroid plexus. The use of CSF specimens has been of tremendous value in the diagnosis of CNS infections but the rarity of pathogens/antigens in the CSF in some of the parasitic infections such as neurocysticercosis, cerebral toxoplasmosis, granulomatous amoebic encephalitis due to llenging ,2. For sllenging -5. Physillenging . The BBBThe authors declare that they have no competing interests.Both authors contributed equally to this manuscript and both read and approved its final version.


Alaska's Prince William Sound (PWS) is a unique locale tending to have strong gap winds, especially in the winter season. To characterize and understand these strong surface winds, which have great impacts on the local marine and aviation activities, the surface wind retrieval from the Synthetic Aperture Radar data (SAR-wind) is combined with a numerical mesoscale model. Helped with the SAR-wind observations, the mesoscale model is used to study cases of strong winds and relatively weak winds to depict the nature of these winds, including the area of extent and possible causes of the wind regimes. The gap winds from the Wells Passage and the Valdez Arm are the most dominant gap winds in PWS. Though the Valdez Arm is north-south trending and Wells Passage is east-west oriented, gap winds often develop simultaneously in these two places when a low pressure system is present in the Northern Gulf of Alaska. These two gap winds often converge at the center of PWS and extend further out of the Sound through the Hinchinbrook Entrance. The pressure gradients imposed over these areas are the main driving forces for these gap winds. Additionally, the drainage from the upper stream glaciers and the blocking effect of the banks of the Valdez Arm probably play an important role in enhancing the gap wind. While relatively exposed to open ocean on its southern boundary, to the north, east and west, PWS is embayed by a rugged, elevated, and highly glaciated mountain barrier. In the cold season this barrier tends to separate the cold, dry interior continental air mass from the relatively warm, moist maritime airmass in the northern GOA. Frequently occurring low pressure systems in combination with the high terrain act to induce a variety of strong off-shore and along-shore local winds , 25. In Exxon Valdez and attendant massive oil spill. While the Exxon Valdez incident did not ultimately result from adverse weather conditions, it brought into sharp focus the potential consequences of navigating the PWS with its highly localized adverse weather conditions [A further unique characteristic of Prince William Sound is that it contains Port Valdez along its north boundary. Port Valdez is the southern terminus of the Trans Alaskan Pipeline System (TAPS). Hence, almost all the crude oil extracted in Alaska transits the full N-S extent of PWS in supertankers en route to ports of call beyond the GOA. The potential perils of such a method of oil transport were partially realized in 1989, with the infamous accidental grounding of the tanker nditions .Gap flows are common and gusty  in PWS. Numerical weather prediction (NWP) models and satellite observations have also been combined to study gap winds. Streenburgh et al.  studied Space-borne Synthetic Aperture Radar (SAR) observed normalized radar cross section (NRCS) depends upon scattering from surface roughness elements within the beam footprint. The NRCS from water represents the roughness of the water body surface which is a non-linear function of near-surface wind stress. With a prior estimate of the wind direction, wind speed can be inverted from the NRCS . Comparihttp://fermi.jhuapl.edu/sar/stormwatch/web_windThese SAR images are found online at This site archives a vast number of the near-surface wind field images associated with a wide variety of mesoscale and synoptic-scale atmospheric phenomena. Using this rich archive, several studies have investigated boundary layer convection , gap floThis study uses SAR wind imagery from the JHU APL archive and a high-resolution  mesoscale model to document gap winds for gaps of small lateral dimension in PWS. Section 2 describes two cases of gap winds captured by SAR in PWS. Section 3 presents the mesoscale modeling of these two events. Section 4 discusses the simulated characteristics of the gap wind, and is followed by the conclusions in Section 5.2.The Valdez Arm is a north-south trending gap located in the northern coast of PWS while the Wells Passage is a broader east-west oriented sea level gap  among th-1 range. Relatively weak westerly winds dominate the PWS suppressing the northerly channeled wind exiting the Valdez Arm. The boundaries between the westerly flow and the north-easterly flow are clearly shown as a narrow zone of weak wind on the image.  -1 in the Valdez Arm and a westerly strong gap wind of approximately the same strength from the Wells Passage. These two perpendicularly aligned jets meet near the center of the PWS. The combined wind jet further extends southeastwards out the PWS through the Hinchinbrook Entrance with a weaker speed of 15 ms-1. The extension of the Wells Passage jet turns right as the result of pushing from the Valdez jet and the right-turning nature of a gap wind [The gap wind . Note, agap wind , 25.  Eta model.We used the Regional Atmospheric Modeling System (RAMS) as our numerical tool in this study. Developed at Colorado State University and Mission Research Corporation, RAMS is a multipurpose numerical simulation system , 3. It i3.2-1 in the Valdez Arm and a weaker flow, 7-9 ms-1, in the Wells Passage. Note the model time is about 1.5 hours earlier than the corresponding SAR wind image. The reason for choosing the simulation of this time is that the RAMS wind most closely resembles the SAR wind  is more close to the east bank. The streamlines in The streamlines in  feature , 5, 25. 4.2The Valdez Arm is surrounded by elevated, often glaciated, terrain from which cold dense air tends to pour into the Arm in the cold season. The two cases studied here illustrate that the leeside winds, blowing into the Arm from surrounding areas, play an important role in fueling the jet in the Arm. 5.High resolution SAR wind imagery and a mesoscale model were combined to better understand gap winds in the PWS. SAR wind imagery reveals detailed wind features over the water body surface while numerical mesoscale model simulations can be used accordingly to understand the highly localized atmospheric interactions over complex coastal terrain. Our focus was on the northeasterly gap wind in the Valdez Arm which is the largest northerly gap in PWS and the origin of the oil tanker route to the continental USA. The SAR wind imagery revealed the gap wind's areal extent and resembled the mesoscale model simulations. The high resolution mesoscale model simulations revealed that the Valdez gap winds were fueled by the down slope winds from the elevated areas surrounding the Arm. Both the weak and strong cases of this gap wind regime showed indications of a barrier jet, stronger winds adjacent to a physical barrier. The west-east vertical cross-sections crossing the middle of the Valdez Arm showed the air is descending on the eastern and rising on the western part of the Arm. The blocking of the barrier induced the upward motion of the air on the western part of the Arm. The eastern bank of the Arm also served as a barrier which accelerated the gap wind in the strong wind case. The westerly winds from the Wells Passage have a significant impact on the Valdez gap wind, especially when the northerly flow is weak. The westerly Wells Passage winds turned southwesterly into the Valdez Arm and suppressed the development of the Valdez gap wind. In an ideal case, pressure gradients are solely responsible for a gap wind, but in “messy” complex coastal areas multiple mesoscale mechanisms likely act in combination to dynamically impact the gap wind. With the addition of SAR-wind imagery, a high-resolution mesoscale model can be used to reveal several of the 3 dimensional details of these interactive flows.The Alaska SAR demonstration project has found many applications ranging from atmospheric boundary layer measurements, oceanic measurements and sea ice observations  — wind r


Schizophrenia is a complex disorder that manifests on many different levels ranging from the physiology of single neurons thorough the dynamics of neural circuits to cognitive, affective or behavioral symptoms. We use a multi-level approach to connect these different levels. Our previous results demonstrated the schizophrenic patients show a significant impairment in object-location associative learning tasks . Here we developed a neural network model incorporating brain regions involved in paired-associate learning in order to analyze the mechanisms underlying behavioral differences between schizophrenic patients and control subjects.A feed-forward network creates the representations of the identity of the object and its location in the model of the area IT and SP in the ventral and dorsal visual stream, respectively. The proposed role of the hippocampus is to bind these two representations together so that when cued by the location, the correct object can be recalled. Moreover, in order to model cognitive control, we included a prefrontal region which controls learning and recall processes presumably by modulating the plasticity and the efficiency of hippocampal synapses. We fitted the model's performance to the behavioral data Fig. . Our modSecond, using a high-level probabilistic approach to model fMRI data recorded from the patients, we tested the predictions of the neural network model Fig. . We defiIn conclusion, prefronto-hippocampal interactions are material in understanding learning impairments in schizophrenia, and our multi-level approach is suitable to integrate the explanatory capabilities of mechanistic neural models with the analytical power of data-driven phenomenological approaches.


Tumors of the pancreatic head can infiltrate the superior mesenteric vein. In such cases, the deep veins of the lower limbs can serve as suitable autologous conduits for superior mesenteric vein reconstruction after its resection. Few data exist, however, describing the technique and the immediate patency of such reconstruction.En bloc resection of the tumor was performed with resection of the superior mesenteric vein and reconstruction. A 10 cm segment of the superficial femoral vein was harvested for the reconstruction. The superficial femoral vein segment was inter-positioned in an end-to-end fashion. The post-operative conduit patency was documented ultrasonographically immediately post-operatively and after a six-month period. The vein donor limb presented subtle signs of post-operative venous hypertension with edema, which was managed with compression stockings and led to significant improvement after six months.We present the case of a 70-year-old Caucasian man with a metachronous metastasis of colon cancer and infiltration of the uncinate pancreatic process, on the anterior surface of which the tumor was located. In cases of exploratory laparotomies with high clinical suspicion of pancreatic involvement, the potential need for vascular reconstruction dictates the preparation for leg vein harvest in advance. The superficial femoral vein provides a suitable conduit for the reconstruction of the superior mesenteric vein. This report supports the uncomplicated nature of this technique, since few data exist about this type of reconstruction. Though pancreatic metastases from colorectal cancer are very rare and the mid-term results of surgery have not been clearly defined yet, pancreatic resection has been suggested in selected patients with isolated metastases from colorectal cancer and/or limited extra-pancreatic disease ,2.The most common unexpected finding at the time of pancreaticoduodenectomy in pancreatic carcinoma of the head and uncinate process is the invasion of the superior mesenteric vein (SMV) or superior mesenteric portal vein (SMV/PV) confluence, located anteriorly, laterally, or posterolaterally ,4. The cA 70-year-old Caucasian man with a history of right hemi-colectomy one year earlier (due to adenocarcinoma of the right colon) was admitted to our hospital with abdominal pain and unexplained weight loss. His laboratory values, X-rays, and computed tomography (CT) were not indicative of any distinctive pathology. Therefore, the general surgeons decided to proceed with an exploratory laparotomy, based on the patient's recent hemi-colectomy and the high clinical suspicion of a metachronous metastatic insult of the pancreas.A metastatic tumor was identified in the uncinate process of the pancreas. During the dissection and preparation, the SMV involvement was identified on its anterior surface superiorly to the confluence of the middle colic vein at the level of the transverse mesocolon. No involvement of the superior mesenteric artery was identified. When it was decided that the tumor could be resected with a sufficient macroscopic margin, a duodenopancreatectomy was performed. Sufficient resection with healthy margins was documented by intra-operative histology. The tumor adhered only to the SMV, with the latter caudally divided at the point where the SMV emerged.Accordingly, a right mid-thigh incision was performed, and an adequate SFV segment up to the junction with the profunda femoris vein was harvested. The duration from the vein preparation and harvest to skin closure was 15 to 20 minutes. During the venous reconstruction, a solution of 5000 U of heparin was delivered locally through the SMV. No valvulotomy was performed. The pancreatic head resection was immediately followed by the construction of a proximal anastomosis between a non-reversed SFV segment 3 cm to 4 cm in length and the central stump of the SMV in an end-to-end fashion . During the immediate post-operative and follow-up phase (six months), only mild edema of the leg was marked. The SFV inter-position graft showed good patency Figure  on colorPancreatic resection is sometimes combined with reconstruction of the major veins with venous grafts . The veiet al. [Several types of conduits have been utilized for the reconstruction of the SMV, including mostly autogenous vein grafts and, in some cases, synthetic polytetrafluorethylene grafts. The avoidance of the infection risk regarding the pancreatoduodenectomy favors the autogenous conduits. Apart from the commonly used saphenous vein (SV) and SMV, autologous reconstructions with the internal jugular vein, left renal vein, and gonadal veins have also been reported. The SFV provides an excellent size match (7 mm to 12 mm in diameter and 40 to 50 cm in length) for the SMV/PV site compared with the SV . GeneralImmediately post-operatively and after six months, our patient had only mild edema and no discomfort. There seemed to be no significant difference in the measurement of the circumference of the harvested limb compared with the unharvested limb . As long as the SFV harvest does not extend into the popliteal segment and the profunda femoral vein is preserved, the generation of severe venous hypertension and the consequent need for prophylactic fasciotomies is precluded. The minimal mid-term to late-term lower-limb venous morbidity could be attributed to the preservation of collaterals and the low incidence of mild reflux despite the venous outflow obstruction, provided that the venous valves are intact and competent. The deep vein harvest results in venous outflow obstruction. This in turn generates pooling of blood in the periphery and consequent poor apposition of the venous valve leaflets, leading to functional venous reflux, thus underscoring the clinical utility of compression stockings. These pathophysiologic features could explain why SFV harvest is so well tolerated in contrast to the valve damage caused by venous thrombosis.The SFV can be an excellent conduit for SMV reconstruction because of its size and availability, good mid-term patency, and low peri-operative and post-operative venous morbidity. Surgeons should be aware of and prepared for the unexpected need to perform venous reconstruction with a SFV conduit. Adherence to technical perfection makes SFV an excellent conduit with minimal morbidity.SFV: superficial femoral vein; SMV: superior mesenteric vein; SMV/PV: superior mesenteric portal vein.Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.HG conceived the study concept and design and was involved with the patient's care. EG, JT, and KP were involved in the formation of the study concept and design, patient care, the drafting of the manuscript, and the literature review. CS and HG carried out the operation on the patient. All authors read and approved the final version of the manuscript.


Comèl-Netherton syndrome is an inherited ichthyosis that is associated with highly impaired epidermal cornification and barrier function. Literature sparsely reports of the occurrence of early onset skin cancer in people with Netherton syndrome. To the best of our knowledge the suitability of the severely altered skin in patients with Netherton syndrome for techniques of facial plastic reconstructive surgery has not been discussed in literature yet.We present a 31-year-old caucasian female patient with Netherton syndrome who developed a defect of the right nasal ala. Biopsy revealed a well differentiated squamous cell carcinoma.We describe the reconstruction of a full thickness nasal defect with a paramedian forehead flap and an epidermal turn-in flap in Netherton syndrome. Despite the altered skin texture, reconstruction and healing were uneventful and the surgical result was favourable.Therefore the authors state that the development of cutaneous malignancies should be included as a possible complication in patients with Netherton syndrome. Standard techniques of surgical facial reconstruction can be applied in these patients; healing and outcome do not appear to be negatively affected by the underlying disease. Comèl-Netherton syndrome (= Netherton syndrome), first described in 1958, is a rare autosomal recessive disorder belonging to the group of inherited ichthyoses . ChavanaThe manifestations of Netherton syndrome range from mild disease with ichthyosis linearis circumflexa Comèl to exfoliative erythroderma, which can end fatally within the first days postpartum. A predominance of female patients has been reported. Further complications of Netherton syndrome include mental and growth retardation and aminoaciduria. Hyperimmunoglobulinaemia E, high levels of complements (C3/C4) and a reduced number of natural killer cells make the patients susceptible for recurrent infections and allergic reactions like angioedema, hay fever and food allergies .Several papers reported the development of cutaneous neoplasia in patients with inherited ichthyoses like keratitis-ichthyosis-deafness syndrome, congenital ich-thyosiform erythroderma and lamellar ichthyosis . HintnerStandard techniques of full thickness nasal defect reconstruction include epidermal turn-in flaps and placement of paramedian forehead flap in staged procedures . Each ofIn this report we present a case of nasal defect reconstruction in a young female with nasal skin malignancy in Netherton syndrome.A 31-year-old woman with Netherton syndrome diagnosed in childhood was referred to our clinic for evaluation and treatment of an atrophic defect of the right ala of the nose. The patient reported that the lesion began to develop with a small scab approximately four weeks ago and developed into an expanding, painless ulcer. She denied trauma and factitious manipulation. Patient history included previous hospital admissions for systemic and topical treatment of the underlying disease, and a consanguin marriage in former generations.On clinical examination the patient’s skin was erythro-dermic, xerotic and scaling. On palpation, however, the skin-soft tissue envelope appeared soft and pliable. The patient had chapped and rough lips, easily starting to bleed when opening the mouth. Moreover she had dry, brittle and bristly hair and almost no eyebrows and lashes. There was an endophytic 4 millimeter ulcer of the right nasal ala as shown in Figure The histologic evaluation of a biopsy from the edge of the defect showed a well-differentiated squamous cell carcinoma. Ultrasonography of the neck revealed no suspicious lymph nodes.The tumor was resected under local anaesthesia, minimal margin was 4 mm on permanent histologic section. In terms of reconstruction, we discussed with the patient various options including single – stage placement of a composite graft, and a staged reconstruction with an epidermal turn-in flap and a paramedian forehead flap with the option of a third stage thinning of the flap, if needed. The patient opted for the staged approach. In the first stage, inner lining was reconstructed with two epidermal turn-in flaps of the right nasal sidewall. The skin texture and thickness appeared not ideally suited for the transposition of a nasolabial flap, and hence a paramedian forehead flap, based on the supratrochlear artery was selected for epithelial closure Figure . The donPedicle division and contouring of the flap was performed in the secondary constructive stage 3 weeks later under local anaesthesia. Wound healing was unremarkable. The patient has remained free of disease for 11 months follow up . Some authors speculated about an association between the cutaneous malignancies and the presence of HPV . HoweverSerine protease inhibitor which is affected by mutations of SPINK5 gene in Netherton syndrome, was shown to be a protective factor in breast cancer. A lack of serine protease inhibitor impairs the skins potential of DNA repair and therefore possibly also contributes to cutaneous carcinogenesis .Another factor for the susceptibility to squamous cell carcinoma in Netherton syndrome patients could be the multiple treatments with aggressive medication like in-terferon-alpha, retinoids, methotrexate, corticosteroids or PUVA ), which is known to induce mutations of the tumor suppressor protein p53 . All theFrequent infections and the extensive use of topical and systemic medication may adversely affect wound healing. In addition, the chronic state of inflammation suggests a less than optimal environment for facial reconstructive surgery. On the other hand, the palpable softness and pliability of the skin-soft tissue envelope in the present case encouraged the consideration of surgical reconstructive options. Neither technique of dissection nor timing of surgical staging or post-operative wound care were altered in the present case. Wound healing was unremarkable in the sense that the chronic erythema and scaling of the skin remained stable and no delays or deficits of healing were observed. The cosmetic and functional results appeared very favorable Figure .A review of literature as well as the present case suggests an increased awareness for the development of skin cancers in Netherton syndrome. The approach to facial reconstruction in these patients seems not to require fundamental modification despite the clinically obvious marked inflammation of the skin with substantial erythema and scaling. Favorable functional and cosmetic results may be obtained in these patients.Written consent, for publication of the clinical details and clinical images was obtained from the patient. A copy of the consent form is available for review by the Editor of this journal.The authors declare that they have no competing interests.KW carried out the writing of the manuscript, acquisition of informed consent and literature research and approval of all images in the case report. JH helped with her dermatologic background knowledge in outlining and modification of the manuscript. HG supervised, commented and helped in the revision of the manuscript as well as the selection of photographs used in the case report. All authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6815/13/7/prepub


While undergoing the unprecedented urbanization process in the past few decades, China has also experienced a major epidemiological shift from predominantly infectious diseases to chronic conditions. Using data from a national survey of 1,288 respondents in urban China, this study examines the prevalence of chronic conditions and receipt of treatment among urbanized rural residents who have experienced in situ urbanization. Negative binomial and logistic regressions were applied to estimate the differences in chronic conditions, receipt of treatment, and concern of seeking medical treatment among urbanized rural residents as compared to urban residents and rural-to-urban migrants. The results indicate that urbanized rural residents have similar number or prevalence of chronic conditions with urban residents, but they are less likely to receive treatment particularly for cardiovascular conditions. The analysis further reveals that urbanized rural residents are more anxious about their potential inability to cover medical expenses than both urban residents and rural-to-urban migrants. The study stresses the converging prevalence of chronic conditions but the continuing divide in receipt of treatment between urban residents and urbanized rural residents. As China's urbanization continues with the epidemiological transition, there is an urgent need to address such disparities. In the past three decades, China has not only seen the largest human migration in history but also an accelerated process of urbanization , 2. The While undergoing the dramatic economic and social changes in the past few decades, China has also experienced a major epidemiological transition from predominantly infectious diseases to chronic conditions. Chronic, noncommunicable diseases are the leading causes of illness and death , 6. In 2Studies that compare the health status of urban and rural residents indicate that although the prevalences of two-week illnesses and chronic diseases are significantly lower among the rural population, the primary causes of death among urban and rural populations have converged during the past two decades; cancer, stroke, heart disease, and respiratory disease are the top four causes of death in both cities and the countryside . PreviouThe cost of treating chronic disease continues to grow high in China . High mehukou (household registration) status has not been changed, leaving them unable to receive the social benefits associated with urban hukou. Some of these residents do not have health insurance; others are still enrolled in the New Rural Cooperative Medical Scheme. The prevalence of chronic conditions and receipt of treatment among such residents is likely to follow a different pattern and therefore require research and policy attention.Experience of urbanization can have both positive and negative consequences for individual health outcomes. On the one hand, urbanization offers opportunities for improvement in residents' health through better access to health care and service infrastructures; on the other hand, urban expansion also leads to environmental pollution and lifestyle changes that are detrimental to physical and mental health –20. The Using data from a 2011 national survey of urban China, this study addresses two questions: First, what is the prevalence of chronic conditions of urbanized rural residents, and how does it differ from the rate of urban residents and rural-to-urban migrants? Second, what is the prevalence of receiving treatment for chronic conditions among urbanized rural residents, and how does it compare with the situation of urban residents and rural-to-urban migrants? To the best of our knowledge, this is the first study examining the health status of in situ urbanized rural residents who account for significant percentage of the new urbanites in China.hukou status [Data for this study come from the Migration and Quality of Life survey undertaken in May and June of 2011. Using spatial probability sampling specifically designed technology to reach urban residents regardless of their u status , we firsu status . From thChronic health conditions were assessed with the World Mental Health Composite International Diagnostic Interview (WMH-CIDI). Respondents were asked if they had any of the listed physical and psychophysiological disorders in their lifetime and during the past 12 months. The total number ranges from 0 to 10. The conditions were further divided into four classifications: pain-related, cardiovascular, respiratory, and others. Each of these four categories was coded “1” if the respondent had any of the conditions and “0” if not. Respondents reported whether they received any treatment for each of the chronic conditions during the past 12 months . Respondents were also asked about their concern of seeking medical treatment: “Do you worry about paying medical bills when you have a serious illness?” .hukou), rural-to-urban migrants , and urbanized rural residents . Demographic information included age, gender, and marital status. Measures of socioeconomic status were education, occupation, and household wealth . Health insurance included three dichotomous variables: urban basic medical insurance, New Rural Cooperative Medical Scheme, and commercial health insurance.Migration and residency status was coded into urban residents  and for cardiovascular conditions in particular . When measures of socioeconomic status are further controlled, urbanized rural residents are still significantly less likely to receive treatment than urban residents for cardiovascular conditions ; the odds ratio for any chronic condition is similar (0.30) but statistically insignificant. Similar to urbanized rural residents, rural-to-urban migrants are also less likely to receive treatment for cardiovascular conditions than urban residents, no matter whether socioeconomic status is controlled. There is no significant group difference in receipt of treatment among those with pain-related conditions.P < 0.01). Pain-related and respiratory conditions are significant predictors of the concern. None of the health insurance schemes significantly lessen the concern.Based on data from a national survey of a representative sample of China's urban population, this study for the first time documents the prevalence of chronic conditions and receipt of treatment among those urbanized rural residents who have experienced in situ urbanization as compared to urban residents and rural-to-urban migrants. The results confirm the healthy rural-to-urban migrant phenomenon except on the prevalence of lifetime cardiovascular conditions, but they indicate no difference between urbanized rural residents and urban residents in the average number or prevalence of chronic conditions either during the lifetime or in the past 12 months. The analysis further demonstrates that compared with urban residents, both rural-to-urban migrants and urbanized rural residents are less likely to receive treatment for cardiovascular conditions; however, urbanized rural residents are also less likely to receive treatment for any chronic conditions before controlling for socioeconomic status. In addition, urbanized rural residents are most anxious about their potential inability to cover medical expenses, and none of the health insurance scheme reduces this concern of seeking medical treatment.The prevalence of chronic conditions and the narrowing gap between long-term urban residents and recently converted urbanites, as opposed to the healthy migrant phenomenon, provide us a better understanding of the separate effects of migration and urbanization on health. While the city is drawing 200 million healthy young adults out of the countryside, the city is also rapidly expanding into the countryside and converting 200 million rural residents into urbanites. These urbanized residents are passively merged into the urban life. The findings in this study suggest that, different from those young migrant adults, the urbanized rural residents are not keeping any health advantage as former villagers, but rather catching up the prevalence of chronic diseases as new urbanites. The potential risks of urbanization of the world's most populous nation, including the loss of arable land, the creation of poor urban enclaves, and the deterioration of residents' health outcomes, require a great deal of research and policy attention.hukou is still pronounced. The data for this study show that 62% of urban residents are covered by the urban basic medical insurance, while 80% of urbanized rural residents are enrolled in the New Rural Cooperative Medical Scheme. The majority of rural-to-urban migrants are also in NRCMS. Commercial health insurance is popular only among urban residents.As China's rapid urbanization proceeds at unprecedented scale and pace, the health and economic implications of chronic conditions are likely to be huge and present tremendous challenges. The situation is particularly serious in China where family support has become more precarious because of the one-child policy . The govhukou holders residing in a recent urbanized place. It is likely that during the rapid urbanization process, the area has been converted or merged into an urban district, but the residents there have not changed their hukou status from rural to urban, nor have they acquired the associated social benefits. During the urbanization process, efforts must be made to ensure their hukou transition and access to the urban health care system. Meanwhile, the results of this study show that socioeconomic status, particularly professional or managerial occupation, is an important predictor for receiving treatment for chronic conditions. Resources and employment opportunities therefore need to be promoted to enhance the livelihood and socioeconomic status of urbanized rural residents.The health care access among the group of urbanized rural residents requires further research and policy attention. They are the original rural Furthermore, the efficacy of the existing health insurance schemes in providing treatment for chronic conditions is limited. The findings in this study suggest that belonging to the urban or the rural basic health insurance scheme does not reduce the concern about potential inability to cover medical expenses. Other scholars have also observed that NRCMS offers very limited protection in type of care and reimbursement of health care costs –29. HaviA few limitations should be noted. First, the study focuses on chronic conditions. These health conditions are not always verified by clinical diagnosis and do not represent incident cases. Nonetheless, this measure of health has been used in prior studies and correlated with clinical measures of morbidity . Second,hukou, as well as the anxiety held by urbanized rural residents in paying medical bills. As China's urbanization process continues along with the major epidemiological transition from predominantly infectious diseases to chronic conditions, the group of urbanized rural residents deserves more research and policy attention, and the issues they encounter must be tackled with an integrated approach.Despite the above limitations, this study represents a timely investigation of the prevalence of chronic conditions and receipt of treatment among the group of urbanized rural residents who have experienced in situ urbanization in China. The research stresses the converging prevalence of chronic conditions between long-term urban residents and these new urbanites yet the continuing urban-rural divide in health insurance based on


Cutaneous squamous cell carcinoma (SCC) of the hands and fingers are sometimes locally aggressive; with higher rates of regional metastasis than other cutaneous SCC, although distant metastasis is rare.We present the case of a 62–year-old Japanese man with double cancers: a tongue SCC and a cutaneous SCC. Swelling of the finger lesion developed gradually around the entire remaining middle finger after accidental amputation at the proximal interphalangeal joint. Histopathological examination of the tumor on the stump of the amputated finger indicated a well-differentiated SCC. The past history indicated surgery for SCC of the tongue 3 years earlier; with histopathology of moderately-differentiated SCC.Since dedifferentiation is unlikely in metastatic tumors, the cutaneous SCC of the finger is unlikely to have originated from the tongue SCC. Alternatively, the double cancer may be two unrelated lesions or the tongue tumor could have originated from the cutaneous SCC. Post-traumatic cutaneous squamous cell carcinoma  arising in chronic scars, ulcers and sinuses is not common-3. The dIn 1985, a 37-year-old Japanese man suffered accidental amputation of the phalanx of the left middle finger by an electric saw. The stump of the amputated finger at the proximal interphalangeal joint subsequently healed without any infection. Ten years later, the stump tip started to swell gradually without apparent cause; and progressively increased in size over the following 10 years, around the entire remaining middle finger. However, the patient did not seek medical advice since the growth was never painful. Twenty-two years after the accident, the patient consulted an otorhinolaryngologist for an ulcerative lesion on the left lower aspect of the tongue. The entire glossal lesion was resected one month later. The ulcer size was approximately 1.5 × 1.5 cm and histopathological examination established the diagnosis of moderately-differentiated SCC with individual cell keratinization (Figureen bloc through amputation of the corresponding MP joint; according to the Clinical Practice Guideline for Squamous Cell Carcinoma by the Japanese Dermatological Association. The final pathological diagnosis was well-differentiated SCC (FigureBy 2010, the cutaneous lesion in the middle finger had increased in size gradually over the preceding 3-month period, including ulceration with discharge (FigureCutaneous SCC, a malignant lesion that originates from epidermal keratinocytes, is composed of malignant keratinocytes with the capacity for metastatic spread, and is a well-recognized complication of chronic scars, ulcers and sinuses. In addiMetastatic lesions in the hands and fingers are rare. About two thirds of the reported metastatic tumors of the hand and finger originated from lung and breast tumors; while the remaining 35% originated from the gastrointestinal tract, prostate, kidney, parotid gland, skin, and nasopharynx. HistopaIn some series, SCC of the hands and fingers were reported to be more locally aggressive; with higher rates of regional and distant metastases, than other cutaneous SCC. Most caWe presented the case of a patient with two anatomically separate tumors with a question mark regarding their origins. Perhaps recent molecular pathological techniques, such as comparative genomic hybridization, could be employed in the future to determine the cellular origin of double cancers of similar histopathology.Written informed consent was obtained from the patient for publication of this manuscript and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare no conflict of interest.KU drafted the manuscript and was the main surgeon in charge. TM, KN, DS and SW were part of the surgical team and responsible for the patient postoperative care. HN, MY and HI revised the manuscript and provided medical support. HB participated in the conceptualization and final version of the manuscript. All authors read and approved the final manuscript.


Background. Complete anatomic knowledge including all variations of the inferior laryngeal nerve (ILN) is mandatory for thyroid surgeon. Extralaryngeal terminal division (ETD) of the ILN has significant importance for the safety of thyroidectomy. Material and Methods. Surgical dissection of 200 ILNs was performed on 100 cases. The presence of ETD of the nerve was determined intraoperatively. We propose by a surgical point of view a regional  classification of ETD of the ILN along its cervical course. Results. ETD has been observed in 54/200 nerves (27%). Great majority are bifurcated nerves (trifurcation 2%). Four types of ETD are classified. In type 1 , ETD has occurred near inferior thyroid artery (ITA). In type 2 , division has been found on postarterial segment. In type 3 , division has been located very close to laryngeal entry point. In type 4 , ETD has occurred before the nerve crossing the ITA. Conclusions. ETD of the ILN is a common anatomical variation. The bifurcation occurs in the ILN at various distances from laryngeal entry point. The classification increasing surgeons' awareness may help to simplify identification and exposure of terminal branches. Preservation of both extralaryngeal terminal branches of the ILN has paramount importance for the safety of thyroid operations. The safety of thyroid operations mainly depends on complete anatomic knowledge of the inferior laryngeal nerve (ILN) including all its variations. The nerve has many anatomic variations along its expected and unexpected cervical course. The important one is cervical  branching of the nerve. The presence of many branches and sensory innervations of adjacent tissues by thin branches of ILN has been reported up to 90%. These branches have been established by anatomical studies under direct or microscopic observation , 2. ThesIn this study, we aim to establish the rate of anatomical features and location of division along cervical course of the nerve and surgical importance of extralaryngeal terminal bifurcation of the ILN in series of thyroidectomy cases. We try to classify anatomical location of division point on the cervical course of the nerve. A prospective study on surgical anatomy of the ILN was conducted on 100 patients with surgical diseases of the thyroid gland between May 2009 and September 2012. Patients with reoperative surgery for treatment of recurrent diseases were not included. Total thyroidectomy is the surgical procedure in all these 100 patients. All operations were performed by a single surgeon in order to provide a standard dissection. Main subjects of this study are the presence and incidence of extralaryngeal terminal division of the nerve which are macroscopically observed. Location of this division along cervical course of the ILN is determined. Lateral sides  of the terminal division are also noted during thyroid operations. After freeing and medially mobilizing lateral lobes of the thyroid gland at both sides with classical surgical approach, the inferior thyroid arteries (ITA) were identified, isolated, and a loop of silk suture was placed around arteries for traction. With usual lateral approach, ILNs were identified below the artery and fully isolated at both sides. The nerve is carefully exposed in the trachea-esophageal groove until its laryngeal entry point. The dissection is performed using binocular loupe. If macroscopically and clearly delineated terminal divisions of the nerve are identified along its cervical course, we study anatomical features of these branches.Division of the ILN occurs along its cervical course prior to laryngeal entry. The branches are macroscopically observed during thyroid operations, and they enter separately into the larynx by different points. We propose a regional  classification of extralaryngeal terminal division of the ILN along its cervical course. The classification is based on surgical exposition steps of the entire nerve and on the rate of different location of the bifurcation point. Risk regions for injury to the nerve are also taken into account for classification of extralaryngeal bifurcation of the ILN by surgical point of view. Regions and anatomical location of terminal division is classified basing on two relatively constant landmarks; the neurovascular (ILN and ITA) crossing point and laryngeal entry point of the nerve . Results were obtained from surgical dissection of 100 consecutive total thyroidectomy cases. Two hundred ILNs were identified, isolated, and entirely exposed along their cervical courses until the laryngeal entry. Seventy-seven percent of our patients are females. The incidence and anatomic features of extralaryngeal terminal division of the ILN are the main subject of the study.Extralaryngeal terminal divisions of ILNs were determined in 43 (43%) patients. We observed bilateral division in 11 (11%) patients. Extralaryngeal terminal division has been macroscopically observed in 54/200 nerves (27%). The rate of division of the ILN is 19% and 35% at right and left sides, respectively .The ILNs have been terminally trifurcated (divided by 3 branches) along their cervical courses in 4 (4%) patients unilaterally, 2 trifurcations at right or left sides each. This result reflects an incidence of trifurcation as 2% of exposed ILNs .The location of terminal division along cervical course of the nerve is another remarkable finding of the present study. The cervical course of the nerve is divided by four segments in which the neuro-vascular crossing (the ILN and the ITA) and laryngeal entry points are found as important landmarks for regional classification and location of terminal division of the nerve. Approximately half 46.3%) of the terminal division of the ILN has occurred in arterial region. % of the  Microanatomic studies have shown that the ILN divides intralaryngeal branches to anastomose with branches of the internal laryngeal nerve. Size of these branches has been reported 0.6 mm as diameter . When a Complete exposure of ILN is mandatory to avoid nerve injury and laryngeal muscle palsy. Its anatomic variations threaten nerve integrity even in experienced hands. Our rates (27% of ILNs) of macroscopically discovered extralaryngeal terminal division show that this is a common anatomic variation. Therefore, surgeons frequently encounter bifurcated nerve during thyroidectomy operations. Previous manuscripts have also reported the usualness of this variation , 2, 4, 5Terminal division of the nerve may occur unilaterally or bilaterally at both sides. We generally observed unilateral bifurcation of the ILN in which 75% of our patients have got unilateral variation. Bilateral terminal division of the ILN is relatively uncommon. Bilaterality of this variation has been observed in 11% of our thyroidectomy cases and in 25% of patients with bifurcated nerves. Extralaryngeal bilateral division of the nerve has been reported in a large range of incidence between 3, to 33% –11, 13. In case of bifurcated ILN, anatomical location of division point along its cervical course is crucial in order to securely identify, to properly expose all branches of the nerve, and to protect nerve integrity without inadvertent injury to neural structures. In our study, we determined various locations of division point along the cervical course of the exposed ILN. Approximately in half (25/54) of the bifurcated nerves, the division occurs at or very close to nerve-artery crossing point. Bifurcation of the nerve just adjacent to neuro-vascular (the ILN and the ITA) crossing is the most common location of the division point of the ILN. The division of the nerve occurs distal to the ITA (after nerve-artery crossing) in approximately 1/3 of our cases in which this is found as the second common location along the cervical course of the nerve. Beside these two common findings, we also determined two other locations of the division point. The bifurcation of the nerve seldom occurs proximal to the ITA (before nerve-artery crossing). The division point is uncommonly observed very close to the laryngeal entry of the nerve. Landmarks to delineate cervical segments along cervical course of the ILN: two relatively constant landmarks  help to divide cervical course of the nerve by four segments; pre-arterial, arterial, post-arterial, and pre-laryngeal. Surgical technique to identify and expose the ILN: the ILN is identified at close proximity of ITA by standard lateral approach technique. The nerve dissection begins in arterial region, and is proximally and distally advanced towards laryngeal entry in order to expose the entire nerve. Rates of division of the nerve in various locations: approximately half of nerve bifurcation occurs near ITA.We try to classify anatomic location of division point of the ILN along its cervical course aiming to increase surgeon's awareness. In order to establish an understandable classification some anatomic structures and surgical variables are taken into account. Therefore, anatomic landmarks, surgical technique of nerve identification and exposition, and location rates of division point contribute to the classification of extralaryngeal bifurcation. Extralaryngeal bifurcation of the ILN is a common variation which carries great importance for preservation of its motor function. We think that to be familiar with location of division point of the nerve in its cervical course is significantly helpful to avoid nerve injury. We propose an anatomical classification of extralaryngeal terminal division of the ILN. Terminal division of the nerve is classified by four types.The bifurcation occurs at or very close (−/+  5 mm) to nerve-artery crossing point. The identification and dissection of the nerve generally begins at this point by standard lateral approach. In experienced hands, the nerve is easily found adjacent to the artery. Therefore, this type of bifurcation is also easily identifiable with careful dissection. This location is the most common type of nerve division in our series. Both branches are individually followed until their separated laryngeal entry.After identification of the nerve trunk, the dissection is advanced in both distal and proximal direction in order to display entire cervical course of the ILN. In some patients, nerve bifurcation occurs distally to the artery, near Berry ligament. In our series, the rate of post-arterial  divisionDuring distal dissection of the ILN trunk, another type of bifurcation is discovered at the most distal part of the extralaryngeal ILN. Pre-laryngeal  bifurcatThe dissection of the nerve is also advanced proximal to the artery along cervical course of the ILN. In some patients, bifurcation of the nerve is found at proximal segment of the nerve before artery crossing. Pre-arterial  bifurcat In case of bifurcation of the ILN, the location of motor fibers in nerve branches has extreme importance for preservation motor function. The motor fibers are located exclusively in the anterior branch, and the posterior branch is sensory in function , 9, 11.  Extralaryngeal terminal branches of the ILN can be a potential cause of nerve injury due to visual misidentification. This anatomical variation cannot be predicted preoperatively and might be associated with higher rate of nerve injury . ExtralaExtralaryngeal terminal division of the ILN is a common anatomical variation.The bifurcation occurs in different segment of the ILN along its cervical course at various distances from cricothyroid membrane . In the majority of such cases, the point of division is located near arterial junction (ILN and ITA crossing point). On the other hand, surgeons must take into account that there are also uncommon locations of the bifurcation. The anatomic classification of division point may increase surgeons' awareness of this variation. The classification may also lead to simplify identification and exposure of terminal branches. The ILN must be macroscopically identified and preserved during thyroidectomy in order to prevent vocal cord palsy. Identification, exposure, and preservation of both extralaryngeal terminal branches of the ILN possess paramount importance in order to prevent nerve injury. Misidentification and misinterpretation of the posterior branch as the main trunk of the ILN put the anterior branch and motor fibers under the greatest risk. Inadvertent division of motor fibers may lead to laryngeal muscles palsy despite the surgeon believing the nerve was preserved.


Protein kinases represent one of the largest group of drug targets in humans. All kinase enzymes share a catalytic domain that binds ATP. In recent years, many small molecule ATP-competitive kinase inhibitors have been developed. However, the evolutionary relatedness and structural conservation of these targets often lead to unforeseen cross reactivity.The goal of this work was to develop structure based ATP binding site descriptors that reflect the pharmacological profile of a predefined set of inhibitor molecules. For this purpose, a 3-step procedure was applied. First, a multiple sequence alignment generated by Buzko and Shokat  was adopA dataset of 38 kinase inhibitors with experimental data against 90 human kinases was used to assess the performance of the developed descriptors . PerformOverall, classification based on the sequence of the binding pocket performed best. However, sequence-based methods cannot detect unrelated kinases with similar pharmacological profile. This in turn is the strength of the MIF-based descriptors since these descriptors characterize the geometry of hot spots on the protein and are independent of sequence information. Visualization of binding site hot spots makes this method suitable to rationally optimize the selectivity profile of a compound.