The globally synchronized switch from trivalent Oral Polio Vaccine (tOPV) to bivalent Oral Polio Vaccine (bOPV) took place in Nigeria on April 18th 2016. The country is divided into six geopolitical zones. This study reports the experiences and lessons learned from the switch process in the six states that make up Nigeria’s south-south geopolitical zone.This was a descriptive retrospective review of Nigeria’s switch plan and structures used for implementing the tOPV-bOPV switch in the south-south zone. Nigeria’s National Polio Emergency Operation Centre (NPEOC) protocols, global guidelines and reports from switch supervisors during the switch were used to provide background information for this study. Quantitative data were derived from reviewing switch monitoring and validation documents as submitted to the NPEOCThe switch process took place in all 3078 Health Facilities (HFs) and 123 Local Government Areas (LGAs) that make up the six states in the zone. A total of $139,430 was used for this process. The ‘healthcare personnel’ component received the highest budgetary allocation (59%) followed by the ‘logistics’ component (18%).Akwa Ibom state was allocated the highest number of healthcare personnel and hence received the most budgetary allocation compared to the six states .Validation of the switch process revealed that eight HFs in Bayelsa, Cross-River, Edo and Rivers states still possessed tOPV in cold-chain while six HFs in Cross-River and Rivers states had tOPV out of cold-chain but without the ‘do not use’ sticker.Akwa-Ibom was the only state in the zone to have bOPV and Inactivated Polio Vaccine (IPV) available in all its HFs monitored.The Nigerian tOPV-bOPV switch was successful. For future Oral Polio Vaccine (OPV) withdrawals, implementation of the switch plan would be more feasible with an earlier dissemination of funds from global donor organizations, which would greatly aid timely planning and preparations. Increased budgetary allocation to the ‘logistics’ component to accommodate unexpected hikes in transportation prices and the general inefficiencies with power supply in the country is also advised. The launch of the Global Polio Eradication Initiative (GPEI) by the World Health Assembly (WHA) in 1988 set the stage for global polio eradication –4. The tDespite polio eradication setbacks in Nigeria, the GPEI has made significant efforts towards polio eradication through the use of Oral Polio Vaccine (OPV) i.e. trivalent Oral Polio Vaccine (tOPV), which contains Sabin strains of all three poliovirus serotypes  . The useHowever, attenuated polioviruses in OPV can undergo genetic changes during replication, and in communities with low vaccination coverage, can result in vaccine-derived polioviruses (VDPVs) . These cIn response to the risk associated with tOPV use, WHO Strategic Advisory Group of Experts on immunization (SAGE), together with the GPEI developed a comprehensive long-term plan called the Polio Eradication & Endgame Strategic Plan (PEESP), 2013–2018 , 16. EndSince the eradication of WPV2, cVDPV2s due to OPV2 have for accounted for 94% of the 721 poliomyelitis cases caused by cVDPVs detected between January 2006 and May 2016 . To stopHowever, the cessation of tOPV use also carries some risk for facilitating the spread of undetected or newly emergent cVDPV2s among persons without immunity to serotype 2 polioviruses after the switch.  To stop Nigeria complied with these requirements when she carried out SIAs across the country using tOPV for 3 weeks before the switch to boost immunity against serotype 2 polioviruses. This was coupled with the phased introduction of IPV into the country’s RI schedule well over 6 months before the April/May 2016 global switch period.The tOPV-bOPV switch took place in Nigeria on the 18th of April 2016. This study reports the experiences and lessons learned from the tOPV-bOPV switch process in south-south zone of Nigeria.Nigeria is divided into six geopolitical zones namely: north-east, north-west, north-central, south-south, south-east and south-west. This study documents the switch from tOPV to bOPV in the south-south zone of Nigeria. This zone comprises of six states and 123 Local Government Areas (LGAs) namely: Akwa Ibom (31), Bayelsa (8), Cross-River (18), Edo (18), Delta (25) and Rivers (23). The zone is commonly referred to as the Niger Delta region of the country because it is located (in the southern part of Nigeria) at the point where the ‘Y’ tail the river Niger joins the Atlantic Ocean through the Gulf of Guinea. According to the 2006 census, the population of the south-south region is estimated at 24.6 million people [This was a descriptive retrospective review of Nigeria’s switch plan and structures used for implementing the tOPV-bOPV switch in the south-south zone of the country. Nigeria’s National Polio Emergency Operation Centre (NPEOC) protocols and global guidelines together with reports from switch supervisors during the switch were used to provide background information for this study. Quantitative data were derived from reviewing switch monitoring and validation documents as submitted to the NPEOC.The switch was conducted in such a way that most activities occurred at the Health Facility (HF) level. Switch activities were coordinated at different levels  but final coordination was done at the national level. Clear timelines were given for the implementation of each switch activity and these were monitored using standardized dashboards. The key activities conducted were: establishment of switch committees, training of health workers, sensitization of stakeholders, data management and inventory, production and distribution of data tools and bOPV vials to HFs, switch implementation, switch monitoring and validation, the ‘sweep process’ and tOPV destruction. The ‘sweep process’ was a systematic search conducted in all HFs in an LGA where tOPV vials were found to ensure the complete withdrawal of residual vaccines in that LGA.The Nigerian government established switch support committees at the three levels of government i.e., national, state, and LGA. These committees were responsible for implementing the activities of the national switch plan.Switch committees were established in the states and LGAs on the 12th and 28th of February 2016 respectively. The switch was structured along the polio eradication structure of the NPEOC . The IncKey activities conducted by these committees included coordination, development of switch plan and budget based on global guidelines, adaptation of guidelines, setting up operations centre, training, monitoring and mapping of human resource requirements, supervision and validation. The committees consisted of staff from Ministry of Health (MOH), National Agency for Food and Drug Administration and Control (NAFDAC), and international partners involved in immunization. The switch committees had a schedule of activities and initially met weekly but as the date of the switch approached, the meetings were daily to identify issues and proffer solutions. There were also conference calls between different levels  to obtain real time data on challenges and give solutions.Subcommittees on logistics, communications and mobilization, and data management were also established to monitor bOPV arrival and receipts, adaptation of tools and development of advocacy kits. The NPEOC also assigned Monitoring and Accountability (M&A) officers to state clusters to follow up on the implementation of key activities. These officers provided regular reports to the NPEOC. The data team generated monitoring data and flagged issues of concern to the switch committees, which guided their resolution.Health workers for the switch were trained alongside the supplemental immunization campaign training conducted in February and March 2016. The training explained the importance of the switch and the processes involved in conducting actual switch activities. The importance of timeliness and completeness of each stage of the switch process was also stressed during the training. Other avenues used to train health workers on the switch process were: the monthly state-level Expanded Programme on Immunization (EPI) and surveillance review meetings, heads of health facilities meetings and professional association meetings.Most trainings and meetings focused on the health workers in the public sector. However, it became imperative to meet with private sector health workers, pharmacists, pharmaceutical firms and other health stakeholders on the importance of the tOPV switch because they partner with the government in the provision of quality immunization services.This was done via letters and one-on-one meetings using line-lists of potential persons or facilities that could have OPV. At such forums, the issues discussed were: the importance of the switch and tOPV retrieval methods. Assurances were also given to the HFs and vaccine cold stores that all tOPVs retrieved would be replaced with bOPVs without any financial losses to them.A vaccine management tool was used to monitor tOPV stock. Where there was overstocking, vaccines were redistributed to other facilities to avoid wastage. Activities such as mopping-up campaigns with tOPV were conducted. Physical counts were done regularly at all HFs (that had storage capacity), LGA and state cold stores to track tOPV stock levels. An electronic dashboard was used to track the implementation status of these activities. Progress made was shared weekly with the NPEOC.All states in the zone received bOPV vials, along with data tools, stickers and hazard bags from the national level. Arrangements were made at the state level to procure other needed materials. The materials were moved to the LGAs on the 12th of April 2016 and finally to the HFs.The switch was implemented using the reverse SIA approach and it involved all health workers in the facilities that stored tOPV. The LGAs ensured that HFs were open on the 16th and 17th of April for the collection of all tOPVs. The vaccines were collected in hazardous bags with stickers clearly stating that they were tOPVs up for withdrawal. The ward focal persons from each ward picked up the tOPV vials from the HFs and replaced them with the same quantity of bOPV. Appropriate documentation of vaccine pick-up/replacement was ensured. A search was also conducted to ensure that tOPV vials were not left behind in the facilities.Supervisory plans were drawn and senior monitors/supervisors were used to ensure compliance with the laid down procedures. They also ensured that vaccines were not left behind in the facilities. All collected tOPV vials were moved to designated storage places. This was done using the mechanism put in place by the LGA cold stores for vaccine movement. Vaccines were moved from the LGAs to identified storage spots for destruction in the state capitals.Before tOPV destruction and monitoring by independent validators/monitors, senior switch supervisors in the state conducted further spot checks to assess the quality of the switch and ensured that bOPVs were given to HFs to prevent the disruption of immunization activities. They also ensured that the new data tools were being used to capture bOPV use.Fifty-four validators were sent from the national level to all states in the south-south zone to verify the quality of the tOPV-bOPV switch in each LGA. These validators were independent health workers specifically hired for the switch. Each validator worked for 7 days to verify the quality of the entire switch process. Using standard data tools, they were mandated to visit 10% of all HFs in the LGA and report on several aspects of the switch process.The ‘sweep process’ was conducted in LGAs where validators found tOPV vials after the withdrawal was done. Switch validators assessed 10% of the HFs in each LGA. If tOPV vials were found in any of the HFs visited, an additional 5% of the HFs in the LGA would be visited. Where there were more tOPV vials found, all the HFs in the LGA were then recommended for a sweep, i.e., all the HFs in the LGA would be visited by the validators to ensure the complete removal of leftover tOPV vials.This was the final stage of the switch process, which was done centrally in all states. tOPV destruction was supervised by the state tOPV switch committee and was certified by NAFDAC. The method chosen was the ‘boil and bury’ method where all the vaccines retrieved were boiled in huge drums and buried in dug pits. The process was properly documented and all the vaccines destroyed were accounted for by the LGAs and state.The tOPV-bOPV switch process was a critical step in the polio eradication endgame strategy. As such, adequate plans and budgetary arrangements were made to successfully implement switch activities in the 3078 HFs spread across 123 LGAs in the south-south zone of Nigeria  played an important role in facilitating and ensuring the success of the switch program. Table A total of 1963 healthcare personnel were used to facilitate the switch process and $82,622 was used to finance their activities.Akwa-Ibom state used the most (458) healthcare personnel and as such, received the highest budgetary allocation of 21%. Rivers state closely followed this with 417 healthcare personnel and a budgetary allocation of 20%.Bayelsa state utilized the least healthcare personnel (143) and as such, only got 6% of the overall budgetary total. Edo and Cross-River states followed this with 270 and 274 healthcare personnel respectively. They received 16% and 17% respectively of the zone’s budgetary allocation.Table In the south-south zone, 391 HFs were monitored and 2% of them had tOPV within active cold-chain. The states with their respective HFs implicated were: Bayelsa (2), Cross-River (4), Edo (1) and Rivers (1). Also, 2% of the total HFs monitored had tOPV out of cold-chain but without the ‘do not use sticker’. The states and their corresponding HFs implicated were Cross-river (1) and Rivers (5). However, 205 HFs had bOPV replaced and IPV was available in 131 HFs. In total, 18,701 tOPV vials were withdrawn from this zone during the switch validation process.Vaccine withdrawal activities across the different administrative levels of the south-south zone were illustrated in Table At the state administrative level, there were no tOPVs out of cold-chain lacking the ‘Do not use’ sticker. All the state cold stores in the zone had also completely replaced tOPV with bOPV stocks. However, only 50% of the required IPV stock was available at the Delta state cold stores.At the LGA administrative level, tOPV in cold-chain was found in 11% of the 18 stores in Cross-River and 4% of the 24 stores in Delta state. About 6% of the stores in Cross-River state, 4% of the stores in Delta state and 23% of the store in Rivers states had tOPV out of cold-chain but without the ‘do not use’ sticker. bOPV was completely replaced in all the LGA cold stores in the zone except for the Delta and Edo state LGA cold stores that had 91% and 93% availability for bOPV in their cold stores.IPV was available in only 17% of the LGA cold stores in Cross-River state, 13% of the LGA cold stores in Delta state, 80% of the LGA cold stores in Edo state and 82% of the LGA cold stores in Rivers state. The LGA cold stores in Akwa Ibom and Bayelsa states had 100% availability for IPV.Table The ‘sweep process’ was ordered in two states: Bayelsa and Cross-River states. These states consist of 26 LGAs  and 814 HFs .The ‘sweep process’ was conducted in two of the 26 LGAs in both states (one LGA per state). Switch validators visited six HFs  in these LGAs during the ‘sweep process’.The globally synchronized tOPV-bOPV switch process was a key milestone in the efforts to eradicate poliomyelitis because it marked the last step needed to eliminate all serotype 2 polioviruses. As of June 2017, two separate cases of cVDPV2 possibly associated with inadvertent use of tOPV had been confirmed in the Democratic Republic of Congo (DRC) . This evThe tOPV-bOPV switch process took place in Nigeria on the 18th of April 2016. The switch was conducted in all 3078 HFs and 123 LGAs that make up the six states in the south-south zone.  and the subnational levels on the progress of the switch process, the timely dashboard analysis and real-time feedback from the health workers in the HFs, the weekly update on the switch process from the lower level (LGA) to the higher level  and the weekly tracking of the states with residual tOPV vials. All of these contributed to the overall success of the switch in both the zone and country.The experience gained from implementing a successful switch in the country has offered valuable insights on how to improve Nigeria’s EPI, and how to prepare for the eventual withdrawal of bOPV after polio has been eradicated.Moving forward, we recommend the timely declaration and dissemination of the exact amount of money available for future OPV withdrawal activities by the global partners and for the timely notification of relevant stakeholders within the country of such activities. This ensures early/timely budgetary adjustments and engagements in the necessary resource mobilization activities. We also suggest that more allocation be given to the ‘logistics’ budgetary component (which covers transportation/vaccine movement) to accommodate unexpected hikes in transportation prices and inefficiencies with the country’s power supply.


Dear editor,Scar hyperplasia and contracture may occur both during the spontaneous healing process of burn injuries and after surgical correction of burn-injury-related hand dysfunction or deformity such as ulnar claw. PressureFirst, traditional gloves are finger closed that cannot adequately keep fingers straight when patients are sleeping or lying in bed. They are also associated with low patient compliance and difficulties being applied to the areas of anatomical flexures because of high-frequency movement. Splints that are designed to stretch tissue scars, prevent scar contractures, and correct the underlying problems may compensate for the inability of traditional pressure gloves to hold fingers in straight positions. However,Another drawback of the conventional finger-closed gloves is the inconvenience in checking up and evaluating the circulation in the distal end of the finger .To overcome this inconvenience, we made another modification of the traditional pressure gloves by cutting the distal end of each finger open, thereby allowing for easier inspection of the circulation in the fingertip by doctors Figure .Figure 2


This citizen-science project is the first systematic study of patterns of spring migration of Maine migratory birds. A comparison of arrival data from the Maine Ornithological Society from 1899–1911 with the modern data (1994–2017) collected for this study indicated that most species are now not arriving earlier, contrary to the predictions of earlier arrivals in the face of global warming. Arrival was synchronous across the lower two-thirds of the state for most species, although some species showed delayed arrivals along the northeastern coast compared to southern coastal areas. Only thirteen of 81 species are now arriving earlier and seven arriving later. Using quantile regression analysis with three levels of tau, the effect of year, temperature-departure from mean monthly temperature and the North Atlantic Oscillation Index were weak. Most species did not respond to any of these explanatory variables using the modern data. Leaf-gleaners showed the strongest responses. Only four species showed increasing abundance in recent years, an effect that influences detectability and hence could confound interpretation of changes in arrival date. The roots of the science of phenology can be traced back to the early 18th century in Britain and Sweden, with the first documentation of the arrivals and departures of British migratory birds . These eThe phenology of spring arrival dates and fall departure dates has contributed greatly to our understanding of the patterns of bird migration ,7,8,9,10Abies balsamea) growth in the spring is initiated 12 days earlier in southern Maine than in northwestern Maine [In this contribution, I examine 24 years of data on spring arrival dates of migratory birds. This project was first conceived with the goal of elucidating the nature of spring migration in Maine. Maine spans a distance of 515 km from south to north, and varies in altitude from sea-level to 1606 m. Pronounced variation in plant phenology occurs along these gradients. The frost-free period in south coastal Maine is 170 days compared to only 80 days in northwestern Maine . Balsam rn Maine . It is tAlthough two treatises on Maine birds have been published ,15, no sThe data for this project come primarily from volunteer observers across the state of Maine. Each volunteer was given an observation form and was asked to record the first arrival of any of 126 species of Maine migratory breeding birds. The observer also provided the geographic location of each sighting by identifying the Biophysical Region in which the sighting was made [The dataset consisted of 64,373 arrival dates for the 126 species. Over 400 observers contributed data over the course of the study.To determine how the wave of migration spreads across the state of Maine, I used the programming language R to perform one-way analyses of variance (ANOVA) for each species to compare mean arrivals in different Biophysical Regions. Because of limited sample sizes for some regions , I restrt-tests in R.To compare arrival dates from the present study with historical records, I took advantage of the arrival dates reported in The Journal of the Maine Ornithological Society over the lifetime of the publication (1899–1911). My students and I extracted over 3000 first-of-year dates for 82 species. We combined the data for these years and compared them by species to the combined data of the modern data (1994–2017) using two-tailed, unpaired Student’s Three independent variables were tested for their power in explaining patterns of arrival for 112 species over the 24-year period. First, the year was used, with the prediction that arrivals would show a negative relationship with time, consistent with earlier arrivals as warming of the climate proceeded.https://www.ncdc.noaa.gov/) for measurements of temperature-departure from the mean monthly temperatures. I chose 12 weather stations in the southern two-thirds of Maine, averaging the departure of each station from the monthly average to yield a grand mean for each month.Second, the departure from average monthly temperature in each year was established as an independent variable. Because regional temperatures are correlated from Maine as far south as Delaware , migratiSetophaga coronata) whose mean arrival date is 28 April.The National Climatic Research Center only provides monthly temperature-departure data, precluding the use of time intervals tailored for the migration duration of each species. The month used for comparison depended on the mean arrival date of each species. For example, March temperature-departure data were used for Red-winged Blackbird  and May temperature-departure data for Swainson’s Thrush . The majority of first arrivals for each species occurred over a two-week interval. If the mean arrival date of a species was within six days of the end or beginning of a month, I used the mean of the two consecutive temperature-departure means. As an example, the mean of the April and May temperature-departures was used to analyze the arrival of Yellow-rumped Warblers  can be used to predict the severity and snowiness of winter in northern North America and western Europe. NAO indices were taken from Quantile regression was used to test the effect of these three variables on arrival dates. Quantile regression is advantageous because one can detect patterns that are driven by particular quantiles of a distribution . Under tThe analyses were performed in R using the quantreg package. The model used year, temperature-departure from mean and NAO Index as independent variables.To search for possible relationships between foraging type on changing patterns of arrival, I classified the species into a feeding category . These fhttps://www.mbr-pwrc.usgs.gov/bbs/) for Maine. The BBS provides two trend analyses, one for 1966–2015, and one for 2005–2015. I used 2005–2015 analyses because they are contained within the 1994–2017 interval of the modern data in this study.Detectability of a particular species is influenced by abundance. Species that are declining may have later first arrivals recorded in more recent censuses that are a result of reduced opportunities for observing a first arrival rather than a change in patterns of migration. To control for this possible effect, I used population dynamics data from the North American Breeding Bird Survey (BBS)  and a low of 1429 in 2014. Cumulative means for each species within a year converged within a day or two of the sample mean once 12 to 15 dates were added to the analysis. The sample size of nearly all the species-year combinations exceeded 12 observations, frequently exceeding 30.The intensity of the effort in each Biophysical Region  was a reThe expectation that more observations would be recorded on weekends was borne out by the data  althoughForty-two species showed differences in arrival dates across the five best-sampled Biophysical Regions . SixteenWith tau set to 0.3, fifteen species showed a pattern of earlier arrival over the 24 years of the study with a single species showing the opposite pattern. Fourteen species arrived earlier in warm springs with only one showing earlier arrivals in cold springs. Five species arrived earlier when the NAO Index was high and three arrived later when the NAO was high. With a balanced regression (tau = 0.5), 14 species show earlier arrival over the course of the study with only one showing the opposite pattern. Ten species arrived earlier in warm springs with none showing the opposite pattern. Three species showed arrivals negatively correlated with the NAO Index and none showed a positive relationship.In overview, 37 of the 126 species analyzed showed a significant relationship of mean arrival date with time, temperature-departure from the mean or the NAO Index for at least one level of tau. The most common result was that none of the three independent variables explained arrival date.A few taxonomic patterns are evident . Only onFour species are increasing in Maine based on Breeding Bird Survey data . Such spNineteen species are showing population decreases over the 2005–2015 interval . The decThis project is the first comprehensive effort to understand the patterns of spring bird migration in Maine. With mountains along much of the western border of the state and with more moderate temperatures along the coast, I predicted that birds would likely either arrive first along the coast and spread westward, ultimately reaching the mountains, or that birds would arrive in southern Maine and then fan out, again reaching the mountainous regions last. I also expected a latitudinal effect with birds arriving in southern Maine before reaching more northerly sites.Based on the first four years of the project , patternTo increase the power of the tests, I repeated the analyses using the full 24-year dataset. Only the five best sampled Biophysical Regions were modeled . ANOVAs Some of the first claims of earlier spring arrivals in recent years for eastern North America come from bird clubs or dedicated naturalists who compiled arrival dates every year. Analysis of records from 1903 to 1993 from the Cayuga Bird Club in upstate New York and from 1932 to 1993 from the Worcester County Ornithological Society in central Massachusetts found that all 103 species examined are arriving earlier now . The chaAlthough no such continuous record of arrival dates exists for Maine, the records published in the Journal of the Maine Ornithological Society (1899–1910) provide a yardstick for comparison with the recent 24-year dataset . The mosThe failure to find consistent increasingly early arrival dates in Maine contrasts with the data for Massachusetts and New York ,21,22. PThe data from this project allow testing of patterns of change of arrival dates correlated with time, temperature-departure from the mean for the month of migration and the NAO Index over the period from 1994 through 2017. Premised on the effect of global warming, each of these three explanatory variables should be negatively related to the mean arrival date.Because natural selection should be favoring early arrivals as the climate warms ,26, I usThe 24-year span of this project should be adequate to detect modern changes in arrival date, because some species in New York began to arrive earlier over a 27-year period . The domWeak effects emerged for the NAO Index . The ovePopulation dynamics may influence the power of this analysis. Four species are increasing with Turkey Vulture showing strong negative effects  for all Nineteen species are declining in abundance, making it more difficult to detect earlier arrivals because of reduced encounter opportunities in recent years. Nine of these species show non-significant trends of time and environmental variables on arrival suggesting that population dynamics may be masking a response to climate change.In summary, the data from this citizen-science project indicate about half of the species analyzed show arrival patterns across the state that are consistent with patterns of spring temperature increase along a latitudinal gradient . The imp


Avoidance from palatal blood vessel rupture is a major concern during the palatal soft tissue graft surgery. There is no defined chair-side and case-specific palatal blood vessel detection approach to facilitate the harvesting process. The objective of this pilot study is to assess the feasibility of a near-infrared vein visualization system in the screening process of palatal blood vessels.An extraoral vein visualization device (AccuVein AV400) was applied to a total of 304 hemi-maxilla of 152 individuals by two blind examiners. The study groups were classified according to their maximum inter-incisal measurements. The distances between the coronal border of the vessel image and the mid-palatal gingival margins of the adjacent teeth were measured and in each group. The correlations among the measurements were evaluated within groups.p<0.001). Correlations between the examiners gradually increased in all groups as the mouth opening rates of the subjects were increased (p<0.001).The blood vessel to the adjacent teeth measurements exhibited no statistical difference between both examiners in all subjects (In the current state, screening of the palatal blood vessels via near-infrared vein visualization technology seems to be not suitable for every individual due to the restrictive effect of mouth opening. However, the promising results of this preliminary study demonstrated increasing consistency between the measurements of the examiners as the inter-incisal distance increase which emphasized the need an intraoral version of the device. Considering the lack of local decision-making technology for the detection of palatal blood vessels, further studies are required for development and optimization of these systems. Key words:Near-infrared vein visualization, palatal graft harvesting, surgical complications. Free gingival graft and subepithelial connective tissue graft operations are common periodontal plastic surgery techniques for the management of periodontal and peri-implant soft tissue deformities. Palatal keratinized mucosa is accepted to be the major donor site due to its analogy with the gingiva with respect to tissue characteristics . The sizDamage to the palatal neurovascular bundle (NVB) which comprises greater palatine artery, vein and nerve together may lead several complications during the surgery . NVB injRecent advances in the medical imaging devices allow real-time visualization of superficial veins under the skin  Fig. 1)1). A lasin vivo use of a VVD in screening of palatal blood vessels in order to provide an initial data to test its feasibility.Considering those benefits of this emerging technology, intraoral use of this device to avoid palatal blood vessels can be utilized for real-time screening in palatal soft tissue graft harvesting process for the periodontal plastic surgery. To the best of our knowledge, there is no data in the literature about the use of this system for intraoral purposes and there is no defined case-specific and chair-side methodology for real-time detection of palatal blood vessels. The aim of this pilot study was to evaluate the - Case selectionThe study was approved by the Ethics Committee of the Medical Faculty of Kocaeli University (GOKAEK 2016/55). Study group consisted of 180 voluntary staff members and students of Kocaeli University, Faculty of Dentistry. The study protocol was explained and written informed consent was obtained from all participating subjects.All subjects who had all first and second premolar and molar teeth in their maxilla were included in the study. Third molar existence was not considered as an inclusion criteria. Individuals with a history of palatal soft tissue graft harvesting surgery, presenting any lesion or scar formation on their palatal mucosa were excluded from the study. Subjects with any acute temporomandibular joint problem or any other condition which limits their mouth opening less than 30 mm were also excluded. Inter-incisor distances of subjects at their maximal mouth opening were measured and recorded using disposable paper rulers by the same examiner (Examiner 1). A total of 28 patients were discarded due to above mentioned criteria which may interfere with VVD application process.- VVD application and measurementsAfter case selection, a total of 152 individuals  with 304Both of the examiners performed all investigation procedures independently and were unaware of one another’s results in a blind way. In this regard, all subjects were examined by the investigators within different time periods. Both of the examiners were assisted by different dental assistants who also recorded the measurements separately to evade risk of bias.AccuVeinAV400 vein visualization device  was applied according to the manufacturer’s instructions, from a distance of 10 to 45cm over the surface and was held perpendicularly as much as possible to obtain a clear blood vessel image. Examiners and subjects wore protective glasses before the VVD application as a precaution. The device had two contrast options: i) red vessel image on a black background, ii) black vessel image on a red background. Black vessel image on a red background setting was chosen to identify the vessel image and to prevent superimposition of the mucosa color which is also red Fig. . ConsideDuring the VVD application, the distances between the gingival mid-palatal margin of all upper premolars/molars and the coronal border of the vessel image were measured via rubber stopper attached Williams periodontal probes. The rubber stopper was positioned at the mid-palatal gingival margin of each tooth and the tip of the probe was located at the most coronal border of the vessel image for each measurement Fig. . After a- Statistical analysisp<0.05. Correlations within the examiners were analyzed with Spearman Correlation test. In order to evaluate possible effect of mouth opening rates, comparisons were also made within the groups created based on the mouth opening levels of the individuals . Statistical analysis was performed with SPSS for Windows 15.0 .Kolmogorov-Smirnov normality test was used for testing the normality of the data. Differences between the measurements of the examiners were compared using the Mann-Whitney U test at a significance level of p<0.001). Considering the sub-groups according to the mouth opening rates; correlations between the examiners gradually increased in all groups (p<0.001).The study was concluded on totally 304 hemi-maxillae of 152 individuals, and demographic data and mouth opening rates of the subjects were given in Table 1. Measurements of gingival margin to coronal border of the vessel image of all subjects were presented in l groups  as the mNear-infrared vein visualization technology was developed for the detection of subcutaneous veins to facilitate some medical applications . To the This technology is primarily based on screening of the vasculature of the skin for venipuncture purposes. However, successful detection of arteries using VVDs was also documented . Only hyThe vessel images are obtained within few seconds in real-time. The movements of the patient may instantly affect the quality of obtained images. Making the applications in a dark room may increase the appearance of the vessel images. In addition, red background light was sufficient to differentiate the gingival margins. There was no noticeable difference in the diameters of vessel images with respect to the application distance. Considering the acquisition of blood vessel images from all subjects included in our study, it can be speculated that intraoral use of VVD has a potential to screen the blood vessels of the palatal mucosa.et al. investigated the thickness of palatal mucosa histologically and reported the measurements as 4.42, 4.28, 3.98, 4.85 mm  was considered by us as a more safe method to obtain vessel images as control. However, magnetic susceptibility artifacts (MSA) may complicate accurate detection/differentiation of the palatal vessels using MRI. Due to the proximity of the inspection zone to the bone, there would be high probability of improper detection of these relatively thin blood vessels due to image deformities related with MSA . In addiThe average distances between palatal NVB and the nearest teeth are documented by numerous studies to suggest a safe distance which may aid the clinicians in the determination of surgical borders during the graft harvesting ,8-11. HoOverall, the use of extraoral VVDs seems not suitable for every case in the current state due to the limitation of mouth opening since the most consistent results were obtained in the volunteers with high opening levels in this study. However, according to the promising result of this study, it can be concluded that it may be worth developing and optimizing the intraoral versions of these kind of devices for the detection of palatal blood vessels more accurately in every case in future. In addition, the potential use of VVDs may provide additional surgical confidence to the clinicians especially in the treatment of medically compromised patients who have no luxury to deal with surgical complications.The purpose of this preliminary study is to test the feasibility and consistency of laser assisted vein visualization technology in two-dimensional detection of palatal blood vessels. Although mouth opening exhibited a restrictive effect, increasing correlations were observed among the examiners in locating the palatal vessels. Further studies including the development of intraoral versions of VVDs would be beneficial to evaluate the clinical utility of this approach whether it is useful to reduce complication risks due to patient related anatomical variations in palatal blood vessels as a case-specific approach.


Heart rhythms are generated by complex self-regulating systems governed by the laws of chaos. Consequently, heart rhythms have fractal organization, characterized by self-similar dynamics with long-range order operating over multiple time scales. This allows for the self-organization and adaptability of heart rhythms under stress. Breakdown of this fractal organization into excessive order or uncorrelated randomness leads to a less-adaptable system, characteristic of aging and disease. With the tools of nonlinear dynamics, this fractal breakdown can be quantified with potential applications to diagnostic and prognostic clinical assessment. In this paper, I review the methodologies for fractal analysis of cardiac rhythms and the current literature on their applications in the clinical context. A brief overview of the basic mathematics of fractals is also included. Furthermore, I illustrate the usefulness of these powerful tools to clinical medicine by describing a novel noninvasive technique to monitor drug therapy in atrial fibrillation.


The future of dental education is at crossroads. This study used the parameter of the 2016 Dental Curriculum Hack-a-Thon to assess intra- and inter-institutional agreement between student and faculty views regarding dental curriculums to determine if there is an impact in student perceptions towards dental education from before and after the event.This exploratory, cross-sectional study involved two surveys, with Survey 1 being distributed among four faculty-student pairs of the four participating dental schools answering 14 questions. Survey 2 assessed the views of 20 participating dental students through 26 questions in a pre- and post- event survey design. Descriptive statistics were used to explore differences in perceptions towards dental education across both instrument surveys.The results revealed valuable student insights regarding intra- and inter-institutional agreement relevant for the change in dental curriculum that needs to occur. Survey 2 revealed that mandatory attendance in didactic courses, electronic based examination preferences, and the preference of preclinical courses being held in the first and second years of a four-year dental curriculum were of particular importance to student participants.The results of this study indicate that exposure and participation in subjects pertaining to dental education can be influential on student preferences and opinions on how dental education should be delivered in a four-year curriculum. The current climate in health care is one of reform. Dentistry is not separate from this movement and moreover, dental education should remain a major focus of reform. It is with high standards of scholarship, research, and education that the dental profession can remain at the forefront of quality oral health care delivery. Ensuring the highest standards of education allows patients to receive the highest quality of care. With the changing landscapes of medical education and healthcare delivery, it is imperative that the dental community examines its field not as a separate entity but one included in holistic patient care , 2.In 1926, the Gies report was the first comprehensive review of dental education and made several recommendations for reform , 4. A maThe increasing use of technology, changing pedagogy and soaring costs of dental education have also sparked change –11. Somehttps://en.wikipedia.org/wiki/Hackathon). This can be an educational and social event when participants work collaboratively with a focus on a particular topic and develop innovative projects. At the end of the day/event, each team presents outcomes and often times experts in the field are providing feedback on the feasibility of the project. The “New England Dental Curriculum Hack-a-Thon” event brought pre-doctoral students, post-doctoral students, and faculty from four different New England dental schools together in an integrated way to discuss and debate dental curriculum development. To the best of our knowledge a comprehensive curriculum design program that incorporates student feedback directly has not yet been reported.While the movement toward educational reform has already begun, little is known about the effect of student involvement in curricular development. Recently, the student chapters of American Dental Education Association (ADEA) at Boston University Henry M. Goldman School of Dental Medicine (BUGSDM) Harvard School of Dental Medicine (HSDM), Tufts University School of Dental Medicine (TUSDM) and University of New England College of Dental Medicine (UNECDM) met for the “New England Dental Curriculum Hack-a-Thon” initiative. The “Hack-a-thon” terminology was inspired from computer programming  standards. Each assigned group compiled a 10-min PowerPoint/Keynote presentation that was presented in front of all the participants of the event. In order to facilitate the discussion among the groups and making sure the tasks were completed, each group was assigned an organizer of the event to act as a student moderator. Faculty members, including Deans and Associate Deans, from the four dental institutions were in attendance and together served as judges for the group presentations. Based on specific criteria, the judges ranked the presentations and an award was given to the team that obtained the highest score.During the registration process, one co-investigator explained to all the subjects the purpose of the study at the beginning of the event. Two paper-based surveys were distributed: survey 1 to the faculty member representatives and the student representatives from each institution, that evaluated inter- and intra- institutional agreement; and survey 2 to all the dental students, that evaluated the change in perception after attending the event. Participants were asked to fill out the survey 2 before the start of the event (pre-survey) and then the same survey 2 was given after subjects have attended the event (post-survey). An identification code was given to the “pre” and “post” event surveys to be able to compare the data collected at the beginning and at the end of the event. The surveys were designed to describe the format of the dental education and curriculum that dental students have experienced and their thoughts regarding them. Survey 1 was tested for content and construct validity by the authors, after identifying common themes, based on the previous edition of the event and other references in the literature. Survey 2 was adapted from a previously reported survey . Most ofA blinded investigator computed the participants’ answers to an excel file. Because of the design of this exploratory study, only descriptive statistics (counts and percentages) were reported.Students compiling the four group presentations at the “New England Dental Curriculum Hack-a-Thon” highlighted various topics. Some of the most common topics presented were: decrease lecture time; incorporate more active and modern learning styles i.e. flipped-classroom models and problem based learning; a pass/fail grading system; increase teamwork and peer-to-peer learning; vertical integration; protected elective time for students to pursue individual interests and standardized base curriculum.Survey 1 was completed by four faculty members (deans and associated deans) and four dental students’ representatives (senior students - leaders of each student group at their respective institution), selected by each individual school. All 14 questions were answered by the student/faculty pairs at a 100% response rate. Responses between student and faculty from the represented institutions were compiled, indicating agreement between faculty and students on their perceptions of dental education. Clinical group practice format was the only topic having the same answer response among all students. Faculty agreed unanimously on basic science integration, evidence based teaching, and support of peer-based teaching. Support of the latest dental technologies and style of dental curriculum only had one institution out of the four have its student/faculty pair in agreement. The only topic to achieve the same answer choice between student and faculty of the same institution was inter-professional integration.In Survey 2, of the pre-survey respondents, 20 out of the 20 given the survey responded 100%). The post-survey had only had 18 respondents of the 20 responded, (90%). Different answers were reported pre and post-survey among students regarding mandatory attendance in didactic courses (Question 1), electronic based examination preferences (Question 12), and the preference of preclinical courses being held in the first and second years of a four-year dental curriculum (Question 18). A direct comparison of the agreement regarding the results of the pre-survey and post-survey for the questions that were identified can be further reviewed in Table 00%. The The concordance of students, faculty and staff members in design and implementation of curricula up to the standards of CODA is integral for the successful training of future dental professionals . ResultsSimilarly, faculty across institutions agree that evidence based dentistry are important for the future of dental education. CODA standards require the adoption of evidence-based care in the development of core dental competencies. Adoption of evidenced based clinical care into the core curriculum at dental schools reflects the advancement of dentistry and the push to transform dental care to a more effective/preventative field of medicine. Interestingly, less agreement occurred among students with respect to this topic. Perhaps this reflects a changing tide where the generational expectation is that all care is evidence-based and therefore students do not think that focusing on this area during curriculum development is as important.Group practice model for clinical instruction displayed high agreement across students and also faculty from each institution. This suggests students’ interest in working in teams, rather than as a solo practitioner, reflecting a national trend in greater amount of dentist working in group practices defined by having greater than three dental practitioners caring for a patient pool. Students now need to be prepared for the communication, leadership and conflict management skills necessary to work in a team-based environment.Although inter-professional education (IPE) has struggled to gain momentum in dental education, students and faculty members in our project recognize and value the relationship between dentistry and a variety of other fields of study even if they have yet to experience it , 23. IPE, which suggested the significant value of integrating “student representation and activity under the auspices of reformed International Federation of Dental Education Association (IFDEA)” [Bringing students from different dental educational experiences did encourage dialogue and changes in opinion. Results from survey 2 showed that after engaging with a diverse group overall student opinions did change on several topics. Three survey questions resulted in a significant change. Interestingly, after the workshop, mandatory attendance in the didactic portion of the dental curriculum was not seen as important. Self-directed education and inter-class collaboration permeated all of the presentations and are central in many novel teaching methodologies such as flipped classroom. The common themes of the presentations display an overall debate of individualized learning and competition in exchange for a group learning and team-based model of dental education. The low rate of changes in opinion may reflect a desire for change from all students across all schools participating away from individual learning to team based education. Additionally, since the majority of the participants were inherently interested in dental education, they may all have similar views on the direction of curriculum reform regardless of the school which they attend prior to the workshop. Expansion of similar workshops attracting a wider variety of students not directly involved in dental education would provide a robust data set from which to better understand the effect of group work on student perceptions of dental educational reform. In Europe in the 90’s and in the first years of the twenty-first century, there was a great discussion among many dental schools, as part of the DentEd initiative. The meetings were held among the various European universities, including the Schools of Dentistry, especially before and during the site visits in different schools, and compiled students and faculty feedback. An outcome of the Global Dental Education Congress  – was the workshop report compiled by Divaris et al.(IFDEA)” . Almost (IFDEA)”  It shoul(IFDEA)” .Strengths of this study include the unique setting in which data was collected. To our knowledge, no workshop has been reported wherein students and faculty are brought together to exchange ideas on how best to advance the training of dental professionals. A limitation of this study represents the convenience sample, since the participants were self-interested in dental education. These findings are not generalizable, since the current cohort was representative of the opinions and views of all students/faculty at the participating dental schools, the selection of students and faculty with interest in dental education and positions of leadership related to curricular reform gives an idea of the current trends in curriculum reform. Further studies utilizing representative/generalizable samples should be undertaken to further explore whether the topics presented here hold true across all dental student populations. The current findings could potentially benefit others who might be looking to target specific areas relative to student/faculty perceptions of dental curricula for future research.The results presented in this study may provide foundational data for a potential shift in the future of dental education. This could lead to the development of educational research that further examines the relationships between students, faculty, and dental education regulatory organizations with respect to educational reform. Faculty and students have different opinions in traditional educational methods, but the dental curriculum can implement new systems of teaching basic science and applying principles with a clinical approach that mirrors the medical outlook of comprehensive patient care. The results from the New England Dental Curriculum Hack-a-thon is the first of many events that can open the conversation between students, faculty, and dental educational agencies. This event helped validate that intra- and inter-institutional agreement that student perceptions of their dental education requires feedback and change to improve their understanding in the field of the profession. With more open communication and research, studies like this can help progress dental educational reform and the future of dentistry.


The cardinalized probability hypothesis density (CPHD) filter is an alternative approximation to the full multi-target Bayesian filter for tracking multiple targets. However, although the joint propagation of the posterior intensity and cardinality distribution in its recursion allows more reliable estimates of the target number than the PHD filter, the CPHD filter suffers from the spooky effect where there exists arbitrary PHD mass shifting in the presence of missed detections. To address this issue in the Gaussian mixture (GM) implementation of the CPHD filter, this paper presents an improved GM-CPHD filter, which incorporates a weight redistribution scheme into the filtering process to modify the updated weights of the Gaussian components when missed detections occur. In addition, an efficient gating strategy that can adaptively adjust the gate sizes according to the number of missed detections of each Gaussian component is also presented to further improve the computational efficiency of the proposed filter. Simulation results demonstrate that the proposed method offers favorable performance in terms of both estimation accuracy and robustness to clutter and detection uncertainty over the existing methods. Multiple targets tracking (MTT) is a key technology for many practical applications in both military and civil fields ,2. In moThe main advantages of the PHD and CPHD filters over traditional methods are that they operate on the single-target state space and avoid the intractable problem of data association. In addition, they provide the ability to resolve the uncertainties in both the number of targets and their corresponding states in a cluttered environment. Compared with the PHD filter, the CPHD filter can achieve significant improvements in the accuracy of cardinality estimation and tracking performance ,13. MeanAnother critical issue for the CPHD filter is the high computational complexity arising from the joint propagation of the intensity function and cardinality distribution, which directly depends on the number of measurements with a cubic relationship . TherefoIn this paper, we propose an improved GM-CPHD filter, which aims at addressing the aforementioned drawbacks of the original version. In particular, starting from distinguishing between the detected components and the undetected components, a weight redistribution scheme is introduced into the update step of the filter to compensate the updated weights of the undetected targets, where the information in multiple frames (missed detection or consecutive missed detections) is considered to redistribute the total transferred PHD mass to each undetected target. The resulting filter can effectively reduce the spooky effect in the GM-CPHD filter. Besides, a principled gating strategy is also proposed to improve the computational efficiency of the filter, which adaptively enlarges the gate sizes for undetected targets in the previous iteration to ensure the inclusion of true measurements. Simulation results demonstrate that the proposed method yields favorable tracking performance and good robustness in missed detection and a cluttered environment.The remainder of this paper is organized as follows. In MTT scenarios, the number of targets often changes over time. As a consequence, the unknown multi-target state generates corresponding measurements whose number is also time-varying at each time step. The random finite set (RFS) approach provides a mathematically-elegant treatment of multi-target systems by modeling the collections of target states and measurements as RFSs. For example, if there are fined as ,11:(1)XThe received measurements by the sensor are modeled by:found in .The CPHD filter can be regarded as a higher-order generalization of the PHD filter, which still remains the first-order PHD of the multi-target state, but the higher-order information in target number . Concretgiven by :(5)pk|kGiven the predicted intensity )pD,k(x)Ξk={It can be observed that the CPHD filter still involves multiple integrals in its recursion and admits no closed-form solution in general, except the class of linear Gaussian multi-target systems ,12. For Prediction: Suppose at time The CPHD prediction is given by:After the prediction step, Update: Given the predicted More details on the mathematical derivation about the GM-CPHD filter can be found in . In pracIn the GM representation of the posterior intensity, many Gaussian components will be propagated and preserved at each time step . AssuminNote that the idea of using a tag or a label to serve as an indicator has been adopted in , whereinBesides, considering the possible misdetections for the existing targets, a counter variable Prediction: Since the parameters Update: Given the predicted intensity Let For the components in lysis in , the totIn addition, all of these updated components retain the tags of the underlying predicted components, and i-th component using measurement For the components in  targets . When miD filter ,16, a taBased on the results above, a weight redistribution method is proposed to compensate the updated weights of the undetected components. The pseudo-code of the proposed update process for d out by , the misAlgorithm 1. Pseudo-code for updating the confirmed Gaussian components . Based e degree . TherefoTo evaluate the performance of the proposed GM-CPHD filter, simulations are performed on two-dimensional scenarios generated according to , where t done in , the tarIn this part, we compare the performance of the proposed GM-CPHD filter without gating, the P-GM-CPHD filter, with those of the standard GM-CPHD filter  and the  filters . In addiTo verify the performance of the P-GM-CPHD filter, 500 Monte Carlo (MC) runs are performed on the fixed target tracks presented in Scenarios 1 and 2, but with independently generated clutter and measurements for each trial. For comparison, the corresponding simulations are also performed using the standard GM-CPHD filter and DR-GM-CPHD filter. In addition, we also investigate the performance of the filters under consideration by increasing the clutter intensity to To investigate the influence of missed detection, the tracking performances of the three filters are examined against different detection probabilities under Scenarios 1 and 2 via 500 MC simulations. The resulting time-averaged OSPA distances versus various probabilities of detection under the condition of fixed To compare the performance of the elliptical gating method , the adag=1−10−4  for the It is shown that the high clutter rates and low probability of detections will cause performance degradation, and this phenomenon becomes increasingly evident with the increase of detection uncertainty. The results in This paper proposed an improved GM-CPHD filter, which aims at addressing the spooky effect in the original filter for MTT. More specifically, we proposed a weight redistribution scheme for the filter, which provides an ability to keep the concentration of PHD mass for the undetected targets based on the information in multiple frames. Besides, by exploiting the information of missed detections recorded during the filtering process, an efficient gating strategy that can adaptively enlarge the gate sizes was also proposed to alleviate the computational burden of the proposed filter in cluttered scenarios. Simulations verified that the proposed filter can achieve significant improvements in estimation accuracy and robustness to detection uncertainty, thereby implying an enhanced tracking performance. Moreover, the proposed gating method also showed some advantages over the existing solutions. As future work, extending the proposed filter to a multiple passive sensors system will be an important topic.


After publication of the original article  the auth-Carrillo.In the original article, the hyphen was missed between Vicente and Carrillo and was incorrectly spelt Vicente Carrillo, when the correct spelling was VicenteThe original article has been corrected.


Childhood hearing impairment is a significant cause of disability in developing countries, where infectious diseases are the leading cause of avoidable pediatric hearing loss . The WorThe provision of hearing services in the Pacific Islands is currently limited . AlthougThe WHO reports that 60% of global childhood hearing loss is preventable: prenatal and postnatal infections 31%), birth-related causes (17%), ototoxic medicines (4%), and other causes such as substance abuse (8%) [%, birth-The integration of new pediatric audiology services into existing public health care programs should have a positive outcome if these programs are accepted and well-attended by the community. Given the success of the WHO Expanded Program on Immunization in developing countries, immunization clinics have been identified as an alternative platform for Infant Hearing Screening (IHS) programs in nations where a hospital-based Universal Newborn Hearing Screening Program may not be feasible . The curSchool-screening programs are another well-known public health approach to managing significant health conditions and improving educational outcomes. The development of school-based ear and hearing assessments in the Pacific Islands may collaborate with the WHO Global School Health Initiative to optimize successful implementation of the program . This inThere are a number of challenges  that may prevent attendance at a hospital or health clinic. School hearing screening programs offer an acceptable community-based alternative, and would enable early access to primary health care services for ear/hearing disorders. A key aim of these programs would be to facilitate medical and, possibly, rehabilitative and educational interventions for children identified with a hearing impairment.Hospital-based Ear, Nose & Throat (ENT) Clinics are among the best candidates for the development of public health hearing services for children in the Pacific Islands. Given their existing commitment to otological health care, ENT Clinic staff members are the most likely to appreciate the additional contribution of pediatric audiology services in the overall diagnosis and management of a child with OM-induced hearing loss. ENT Clinic staff members may also have the greatest motivation for acquiring audiometry skills, satisfying the principle of capacity-development in the implementation of locally sustainable services. An opportunity for formal qualifications would be desirable as it provides local staff members with recognition for their skills.Where ENT medical services are accepted and well-attended by the community, the integration of audiometry services into the ear health care framework has been successful. At the time of writing, ENT Registered Nurses in the Solomon Islands and Vanuatu are able to provide audiometry testing as part of their ENT outpatient service. Given that these ENT nurses include a school outreach service as part of their clinical program, the development of an ear and hearing screening program performed by the ENT nurses is a clear possibility. The ENT Clinic may also extend their community-based services to Infant Ear and Hearing Screening programs, targeting early-onset otitis media, and monitoring infants at risk of sensorineural hearing impairment.In addition to community-based public health programs, a hospital-based audiology service should consider the implementation of a hospital-based hearing screening program for survivors of meningitis. Given the estimated burden of post-meningitic hearing impairment in the Pacific Region, the results of a routine hearing screening program for all meningitis survivors could lend extra support to the implementation of immunizations against the multiple causal pathogens of meningitis. A hospital-based hearing screening program may eventually expand to assess other patients at risk of hearing loss .Although the focus of the present review has been a public health approach to reducing the burden of preventable and treatable causes of childhood hearing impairment in the Pacific Islands, some comments about (re)habilitation audiology services are warranted as pilot Infant Hearing Screening programs will identify children with permanent congenital and early-onset hearing loss. In accordance with the principles of international health development, the implementation of (re)habilitation audiology services must consider sustainability. Indeed, the WHO recommends the provision of amplification devices  only where support and maintenance services are also available . The addAlthough many Pacific Island nations have a School for the Deaf or special schools for children with disabilities, the provision of hearing aids for students is limited . While tShould the provision of rehabilitation audiology services be sustainable, there may be more community acceptance of hearing aid services if they are delivered at a School for the Deaf or special school, since a hospital-based service may inadvertently lead to negative perceptions of permanent hearing loss primarily as a disease or illness. Referral pathways should, however, continue to exist between such centres and the ENT Clinic to ensure any additional ear disease is managed as required. Given the tropical climate of many Pacific Island nations, the use of hearing aids increases the risk of otitis externa, as well as cerumen impaction.Another benefit of a school-based service would be that hearing aid care and maintenance are provided by staff in regular contact with the hearing-impaired child. It must be noted, however, that the Pacific Island region is currently moving towards Inclusive Education strategies rather than encouraging separate schools for children with a disability. The Inclusive Education policies are largely based on the fact that attendance at special schools is difficult, and that Inclusive Education is more appropriate given the economic and geographic challenges of the Pacific Island context.The development of pediatric audiology services in the Pacific Islands should consider a public health approach. The integration of childhood hearing services with existing public health initiatives by international organizations such as the WHO and UNICEF, should reduce the burden of preventable childhood hearing loss in the Pacific Islands. Collaboration with the local ENT Clinic, including training and capacity-development of ENT Clinic staff members, is an attractive option in the development of local audiology services for children.


We report a rare case of granulomatosis with polyangiitis (GPA) presenting with hypertrophic cranial pachymeningitis (HCP), abducens nerve palsy, and stenosis of the internal carotid artery (ICA). A 59-year-old Japanese man presented with a year history of nasal obstruction and a 2-month history of slight headache. Histopathological examination of the granulomatous mucosa in the ethmoid sinuses resected by endoscopic sinus surgery revealed necrotizing vasculitis with multinucleated giant cells. The patient was diagnosed with the limited form of GPA as a result of the systemic examination. He declined immunosuppressive treatment. Eighteen months after the diagnosis of GPA, he presented with diplopia and severe headache. Though nasal findings indicating GPA were not observed in the nasal cavity, CT scan revealed a lesion of the right sphenoid sinus eroding the bone of the clivus. Gadolinium-enhanced MRI of the brain showed thickening of the dura mater around the right cavernous sinus and clivus. Magnetic resonance angiography and cerebral angiography revealed narrowing at the C5 portion of the ICA. Intravenous methylprednisolone pulse therapy followed by oral prednisolone and cyclophosphamide resolved headache and dramatically improved HCP and stenosis of the ICA. Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, is a systemic autoimmune disease involving small- to medium-sized vasculitis and necrotizing granulomatous inflammation in the upper and lower respiratory tract, as well as the kidney. Central nervous system (CNS) involvement is uncommon, occurring in 4–18% of GPA patients , and chaA 59-year-old Japanese man presented with a year history of nasal obstruction and a 2-month history of slight headache. Nasal examination showed swelling and crust formation of the bilateral inferior turbinate. CT scan revealed swelling of the mucosa in the bilateral ethmoid sinuses and soft-tissue filling in the right sphenoid sinus  direct extension from nasal and paranasal sinuses to adjacent structures; (ii) vasculitis of the CNS; and (iii) formation of remote granulomatous lesions in the CNS . In the GPA is usually associated with serum PR3- or MPO-ANCA, with the sensitivity and specificity of more than 95% in patients with active generalized GPA . ANCA tiIn the present case, the opportunity to identify HCP and stenosis of the ICA was missed for eighteen months, because we had considered the GPA status of the patient to be stable due to the lack of symptoms and of nasal findings indicating GPA at scheduled follow-up and ANCA negativity. Closure of the opening of the right sphenoid sinus may have worsened the granulomatous inflammation in the sinus and delayed the detection of the disease extension by nasal endoscopy. Ischemic attack was able to be prevented in advance by treatment with mPSL pulse therapy followed by oral PSL and CY. Rapid disease remission can be achieved by any of the treatment strategies that include mPSL pulse therapy, PSL, CY, plasma exchange, and rituximab , 4. PatiHCP and cerebrovascular disorder must be taken into consideration when a patient with GPA present with severe headache and cranial nerve paralysis. Gadolinium-enhanced MRI is quite useful for the diagnosis and follow-up of HCP. The combination of corticosteroid and immunosuppressant is required for induction and remission in patients with GPA.


Food & Nutrition Research (FNR) journal is owned by the Swedish Nutrition Foundation (SNF), a non-profit organisation. SNF was founded in 1961 with the aim of promoting nutrition-related research and its practical application. To this end, the FNR leadership made the bold decision in 2008 to begin publishing electronically as an open access journal and to cease with the printed version. This has accelerated worldwide online distribution and access to the FNR for both authors and readers.The Although the Open Access movement has exponentially increased the number of high-quality journals, there are simultaneous increases in low-quality journals. However, the strong rise in popularity of citation frequency, impact factors and valued credibility component provided by reputable journals prevent the surge of this sort of open-access journals.FNR is now well established as a peer-reviewed, open access journal that strives to briskly review, publish and disseminate high-quality research in nutritional sciences. FNR has recently decided to change the overall focus of the journal to different aspects of human nutrition. The new aims and scope include nutrition ranges from whole-body metabolism, clinical health, fitness and population health and deep mechanistic studies at molecular/biochemical and cellular levels relevant to human nutrition. This scope directly supports SNF’s mission to extend the knowledge of nutrition through basic, multidisciplinary and clinical research to improve public health and clinical practice. Areas of new and added emphasis include the following: eating behaviour and qualitative assessments; nutrition education; implementation; nutrition and exercise physiology; nutritional impacts on cognitive function; intervention programme methods and outcomes; evaluation and validation studies of dietary and nutrition methods; food and nutrition policy; and food processing, packaging and storage affecting nutritional aspects.The major changes for the journal are simplified below:A revised scope encompassing the breadth of human nutrition researchA simplified submission process with the new publishing partner Open AcademiaThe changes in scope demand an expansion of editorial structure to provide the breadth of expertise necessary to chaperone high-quality and rapid peer review. Accordingly, the FNR is now restructured with additional editors with broader expertise in human nutrition and a statistical advisor.I am really excited with the new expanded editorial team and the new publishing partner, Open Academia.I look forward to working with the nutrition community to ensure continued success of this journal.Professor Asim K. DuttaroyEditor-in-Chief


The increasing globalization of the medical profession has influenced health policy, health human resource planning, and medical regulation in Canada. Since the early 2000s, numerous policy initiatives have been created to facilitate the entry of international medical graduates (IMGs) into the Canadian workforce. In Ontario, the College of Physicians and Surgeons of Ontario (CPSO) developed alternative licensure routes to increase the ability of qualified IMGs to obtain licenses to practice. The current study provides demographic and descriptive information about the IMGs registered through the CPSO’s alternative licensure routes between 2000 and 2012. An analysis of the characteristics and career trajectories of all IMGs practicing in the province sheds light on broader globalization trends and raises questions about the future of health human resource planning in Canada. As the medical profession becomes increasingly globalized, health policy and regulation will continue to be influenced by trends in international migration, concerns about global health equity, and the shifting demographics of the Canadian physician workforce. Implications for future policy development in the complex landscape of medical education and practice are discussed. Globalization is not a new phenomenon, but technology and policy development in the past few decades has spurred unprecedented increases in cross-border trade, investment, and migration.Physician migration has grown in the twenty-first century, and Canada continues to be a primary recipient of IMGs.7In the early 2000s, physicians and policy-makers in Ontario predicted a significant physician shortage; tens of thousands of Ontarians were projected to be at risk of having poor access to physician services.As the medical regulator in Ontario, the CPSO issues certificates of registration  to physicians, and monitors and maintains standards of practice to ensure patient safety. The CPSO was a key stakeholder in the Task Force on Licensure of International Medical Graduates that provided recommendations for the entry of IMGs into Canada.traditional licensure route, and it represents the route for the majority of physicians in the province. Beginning in 2000, alternative licensure routes were created for physician applicants who did not meet all the regulatory requirements but who met a series of alternative qualifications set out by the CPSO, primarily for those with recognized training and experience obtained internationally  or the College of Family Physicians of Canada (CFPC)). We refer to this as the ally see . PracticPrevious studies have examined IMGs who are practicing or training in Canada through other policy initiatives, most of whom completed a Canadian residency program and met the traditional licensure requirements in Ontario.The purpose of this study is to describe the physician population in Ontario and highlight how globalization has influenced health policy, medical regulation, and trends in the physician workforce. Monitoring and reporting on the training, practice, and demographic characteristics of various groups of IMGs is an important first step in understanding how globalization and related policy initiatives have shaped the physician population over the last 15 years. The unintended consequences of these policies will be explored and new policy initiatives that have been developed to respond to trends in globalization will be described. As medical education and practice continues to globalize, future policy development will be impacted by steady increases in international migration, concerns about global health equity, and the changing demographics of the physician workforce. Given the constantly evolving nature of this area of research, it behooves researchers and policy makers to continue to mine physician data to inform future policy development at the level of the medical regulator and the health care system.This was a retrospective cohort study using the CPSO Registry database. The analytical sample used was a subset of physicians registered with the CPSO between 2000 and 2012. The CPSO membership includes both IMGs, defined as physicians who received an undergraduate medical degree outside of Canada and the United States, and DMGs , defined as physicians who received an undergraduate medical degree in Canada or the United States. Both Canadian- and American-trained physicians were considered domestic graduates because of the joint accreditation between Canadian and American medical schools.17All physicians can broadly be dichotomized into two categories based on their credentials at the time of licensure: Traditionally Licensed Physicians (TLP) and Alternatively Licensed Physicians (ALP) see . In the All physicians in the analysis held an active licence in Ontario as of March, 2015. Traditionally licensed physicians with a postgraduate training certificate or a restricted certificate as of March, 2015 were excluded from analyses. Alternatively licensed DMGs were also excluded as they were not the focus of the present study.The variables used in this study to describe the demographic and practice characteristics of physicians in Ontario were age at time of registration, sex, location of undergraduate medical school  codes,Ethical approval to undertake this study was obtained from the University of Toronto Research Ethics Board. Data were obtained from the CPSO Registry database and from physician-reported registration files. Descriptive statistics were generated for each of the variables using SPSS.The demographic and practice characteristics of the physicians included in this study are displayed in A total of 11,250 physicians were included in the study. Of the 10,595 traditionally licensed physicians (TLPs), 73% were domestically trained (DMGs) and 27% were internationally trained (IMGs). The 655 alternatively licensed IMGs (ALP-IMGs) accounted for 6% of the total study population. Twenty percent (20%) of the ALP-IMGs migrated to Ontario from another province and obtained licensure either through labour mobility legislation (AIT) or by becoming eligible for the CFPC licensing exams due to prior experience (ALP-Canadian Practice Experience IMGs). The ALP-IMGs who were considered practice ready either through assessment or completion of post-graduate training in a RCPSC-approved jurisdiction (ALP-Practice Ready IMGs) comprised 22% of the ALP group and those who completed North American postgraduate training comprised 58% of ALPs (ALP-North American Trained IMGs).On average, ALP-IMGs were nine years older than TLPs at time of registration (40 vs. 31 years). TLP-DMGs were the youngest (29 years), followed by TLP-IMGs (37 years), and ALP-IMGs (40 years). Within the ALP-IMGs, the Canadian Practice Experience IMGs were the oldest sub-group at 44 years at time of registration.There were proportionally more male ALP-IMGs than male TLPs (59% vs. 49%). TLP-DMGs had the lowest proportion of males (48%), followed by TLP-IMGs (54%) and then by ALP-IMGs (59%). The ALP-Canadian Practice Experience IMGs had the highest proportion of males (73%).The regions of medical school for ALP-IMGs were diverse: those who completed their undergraduate medical degree in the Indian Subcontinent made up the largest proportion (28%), followed by those who trained in the Middle East (17%), the Caribbean (13%), and Eastern Europe (12%). The top five countries of medical school for ALP-IMGs were India, Pakistan, Egypt, South Africa and Iran; the top five countries for TLP-IMGs are almost the same: India, Pakistan, Egypt, Ireland and Iran. Nearly 50% of both TLP-IMGs and ALP-IMGs attended medical school in the Indian Subcontinent and the Middle East. There were slightly more IMGs from Western and Eastern Europe in the TLP group compared to the ALP-IMG group (24% vs. 18%).More TLP-IMGs were trained in countries with a very high HDI compared to ALP-IMGs (23% vs. 13%). The top five countries of medical school for TLP-IMGs from very high HDI countries were Ireland, United Kingdom, Saudi Arabia, Australia and Poland, accounting for nearly 80% of the very high HDI group. Despite the elevated number of TLP-IMGs from very high HDI countries, about half of all IMGs are from countries with a low or medium HDI. While only a small proportion of all IMGs are from very high HDI countries, the majority of these IMGs registered through the traditional licensure route compared to the alternative routes.The practice focus of physicians differed slightly across the study groups. TLP-IMGs had a higher proportion of Family Medicine physicians than TLP-DMGs (57% vs. 47%). There were proportionally fewer ALP-IMGs practicing in Family Medicine (44%) than either TLP-IMGs or -DMGs. The sub-group with highest proportion of physicians specializing in Family Medicine (67%) was the ALP-Canadian Practice Experience IMGs while the ALP-Practice Ready IMGs had the highest proportion of surgical specialists (21%) and physicians practicing in anesthesiology and critical care (15%). ALP-North American Trained IMGs had the highest proportion of medical specialists (21%) and psychiatrists (11%).There were no substantial differences in rurality of practice location across groups; the majority of all physicians practiced in urban centers. TLPs had a relatively higher disparity between urban and rural practices (85% vs. 4%) compared to ALP-IMGs (78% vs. 4%). A higher proportion of ALP-IMGs practiced in suburban areas compared to TLPs (18% vs. 11%). The ALP-Practice Ready IMGs had the highest proportion of suburban practice (24%) and the lowest proportion of urban practice (72%). Approximately 5% of all physicians in this study practiced in northern Ontario. Thirty-three percent (33%) of TLPs in northern Ontario had rural practices, whereas 50% of ALP-IMGs in northern Ontario practiced rurally.To our knowledge, this is the first study that has examined the demographic and practice characteristics of all IMGs practicing in Ontario. By reporting on the IMGs registered between 2000 and 2012, we hope to shed light on the diverse routes to licensure of IMGs in Ontario and highlight some of the intersections between globalization, health policy, and medical regulation.In Ontario, nearly 3,500 IMGs entered the healthcare system in a 12-year timeframe, with 655 IMGs accessing CPSO alternative licensure routes (ALP-IMGs). Of the ALP-IMGs, the majority were ALP-North American Trained IMGs, who entered practice in Ontario by completing postgraduate training in North America. This includes IMGs who trained in the US as well as those who trained in Canada but had not yet written the certification exams at the time of requesting licensure. The second largest subgroup was the ALP-Practice Ready IMGs, who were deemed ready to practice by completing postgraduate training in a jurisdiction approved by the RCPSC  or by undergoing a practice ready assessment in Ontario. Practice-ready assessments were designed for internationally trained medical specialists, most of whom had foreign practice experience prior to entering Ontario.The third sub-group, the ALP-Canadian Practice Experience IMGs who migrated to Ontario from another Canadian province, comprised 20% of ALP-IMGs. This is unsurprising given that Ontario has long had the highest net gain of physicians nationally, while other provinces such as Newfoundland, Saskatchewan, and Manitoba regularly have net losses of practicing physicians.23Multiple studies have demonstrated that smaller provinces provide an entry point for IMGs to practice elsewhere in Canada.All IMG groups were older and had proportionally more males than the TLP-DMG group Earlier comparisons of IMGs and DMGs in Canada have also found these phenomena.These findings highlight the diversity of experience of IMGs and the often circuitous routes to licensure taken by these physicians. They also suggest that IMGs may have shorter careers in Ontario than DMGs since they are older when they enter the workforce. Given that increasing access to licensure for IMGs is intended to contribute to overall physician supply, policies to recruit younger IMGs and reduce potential barriers to entry would allow IMGs to have longer careers in Ontario and have a greater impact on the healthcare system.13The diverse paths of IMGs are evident in the wide range of source countries of IMGs now practicing in Ontario. The majority of IMGs in the present study trained in the Indian Subcontinent, the Middle East, Europe, and the Caribbean. It is worth noting that approximately half of all IMGs are from countries with medium or low HDI, countries that may be in significant need of skilled healthcare workers. According to the World Health Organization, 37% of the world’s healthcare professionals are living in North America despite Canada and the United States carrying only 10% of the global disease burden.31These trends in international physician migration give rise to concerns about global health equity. Increasingly, there is a limited supply of healthcare workers in many low- and middle-income countries and the “brain drain” phenomenon has been the subject of exploration in recent studies.Trends in physician migration also underscores policy questions that have been raised about who should make up the physician workforce in Canada.The practice characteristics of physicians in this study differed slightly by licensure route. Of the physicians who were registered through the traditional licensure route between 2000 and 2012, more TLP-IMGs practiced Family Medicine compared to TLP-DMGs. This may be because prior to 2007, IMGs seeking postgraduate placements in Canada could only apply to the second round of residency matches, at which time most specialty (i.e. non-Family Medicine) placements were already secured by DMGs.However, the ALP-Canadian Practice Experience IMGs, who migrated from another Canadian province, had the highest proportion of physicians specializing in Family Medicine than all other groups. This may reflect the fact that some provinces used to issue provisional licenses to IMGs to practice in underserviced areas, but after two years of practice experience, these IMGs gained eligibility to write the College of Family Physicians of Canada (CFPC) exams and would often move elsewhere in Canada. The trend for IMGs to obtain provisional licenses in one province, practice for two years in order to qualify for a full license in Family Medicine, and then migrate to other provinces such as Ontario has been observed previously.All physicians, regardless of licensure route, practiced predominantly in urban compared to rural locations. Given that increasing physician supply in rural and underserviced areas was a key driver in the development of many health policies, including alternative licensure policies,43Health policies often respond to changing trends in physician demographics and, in turn, the demographic and practice characteristics of physicians influence ongoing policy development. By tracking and reporting on the practice patterns of physicians in Ontario, we aim to contribute to future health human resource planning and facilitate an understanding of the diverse groups of IMGs in the province. This study describes the physicians registered in Ontario between 2000 and 2012, focusing on those who accessed CPSO’s alternative licensure routes. Since 2012, an increasing number of physicians have accessed alternative licensure routes. For example, the number of physicians utilizing the route developed for American-trained physicians has more than doubled in the last three years. Continuing to monitor the characteristics and career trajectories of all IMGs will be necessary to guide effective policy development to be responsive to globalization trends that may impact the medical profession.not successfully obtain licensure. Brain drain from countries with physician shortages often results in brain waste, as many foreign trained doctors are not able to utilize their education and training when they migrate to higher income countries.47One IMG group underrepresented in the literature are the physicians who do Policy development to address physician supply and distribution has always been complex but the evolving nature of globalization compounds these issues. Going forward, policy developers will need to collaborate across systems to carefully consider issues such as global health equity, access to medical education and licensure, ongoing shortages in rural and indigenous communities, and ultimately, the characteristics of the future physician labour force in Ontario. In 2013, the Physician Resource Planning Task Force was developed to coordinate a pan-Canadian health human resources strategy to ensure the appropriate mix, distribution and number of physicians practicing in the country.The ultimate goal of health human resource planning is to ensure that patients receive timely, quality care that is accessible and equitable. In helping to achieve this goal, medical regulators have the challenging role of balancing the provision of access to licensure for physicians while ensuring public protection. The analysis described in the current paper represents the first phase of a comprehensive evaluation focusing on the CPSO’s registration policies and licensure routes. Using the current data for this cohort of IMGs as a starting point, future studies will seek to assess the quality of medical practice of these physicians. Such lines of research may shed light on how regulation can improve integration and education for doctors already in the system and the future resource of internationally trained physicians. The medical regulator is but one player in a complex system attempting to address health human resource challenges in an increasingly globalized landscape. Developing effective strategies to address the above issues will not be easy and will rely on sound research, a willingness to address difficult questions, and a tolerance for the constantly evolving nature of globalized medical education and practice.


Immunological alterations, endothelial dysfunction, and insulin resistance characterize preeclampsia. Endothelial cells hold the key role in the pathogenesis of this disease. The signaling pathways mediating these biological abnormalities converge on PKB/Akt, an intracellular kinase regulating cell survival, proliferation, and metabolism. Inositol second messengers are involved in metabolic and cell signaling pathways and are highly expressed during preeclampsia. Intracellular action of these molecules is deeply affected by zinc, manganese, and calcium. To evaluate the pathophysiological significance, we present the response of the intracellular pathways of inositol phosphoglycans involved in cellular metabolism and propose a link with the disease. Immunological alterations, abnormal placental development, and endothelial cell dysfunction are widely accepted as major determinants for preeclampsia, a severe complication of human pregnancy that may be associated with poor maternal and fetal outcomes . Preeclachiro inositol, two stereoisomers) is involved in metabolic and cell signaling pathways [chiro inositol (DCI), respectively. These second messengers mediate different actions of insulin: IPG-A stimulates lipogenesis, activates acetyl-CoA carboxylase, inhibits cAMP-dependent protein kinase, and modifies the activities of adenylate cyclase and cAMP-phosphodiesterase; IPG-P was shown to exert specific insulin-mimetic properties on the glycogen metabolism through the activation of pyruvate dehydrogenase phosphatase, glycogen synthase phosphatase, and glycerol-3-phosphate acyltransferase  were shown to be highly increased in preeclampsia [At present, the correlation between endothelial dysfunction and metabolic syndrome in preeclampsia is still elusive. A growing body of evidence is emerging to show that the inositol second messenger system . The tw et al., . D-chiroclampsia , 18.Maternal clinical syndrome in preeclampsia (hypertension and proteinuria) derives from an imbalance of circulating angiogenic factors that results in maternal endothelial dysfunction . We havechiro inositol) has a sigmoidal inhibitory action on PDK in addition to its known linear stimulation of PDP [Reversible phosphorylation of proteins regulates many cell functions and abnormal phosphorylation can be associated with altered signaling leading to a variety of pathogenic states. Pyruvate dehydrogenase complex (PDC) is the key interface between glycolysis and the citric acid cycle and is crucial to the generation of ATP, acetyl-CoA, and NADH by mitochondria . The resn of PDP  . These include the differing carbohydrate moieties and structures of the IPG and the binding affinities of their associated trace elements Mnpathways , 25. Thepathways  stated t++ ions may be more significant in the regulation of PDC. Maximal activation of PDP is achieved with 0.01 µM Zn++ but significant activation is still observed at a concentration of 0.003 µM, a value commensurate with the measured content of zinc in IPG-P isolated from rat liver [++ could have significant effects on PDP activity. The higher level of Zn++ required in vitro for the inhibition of PDK may well relate to the association of the enzyme with the mitochondrial membrane in vivo and the requirement for a transport system or catalytic chelators to locate the metal ion at the active site. We feel that these differences in inorganic ion concentration do not necessarily detract from the “push-pull” concept of the IPG-P in the control of the PDH complex but rather from limitations of the in vitro systems used.It has been proposed that the effects of IPG-A and IPG-P containing zinc and manganese may be specifically linked to formation of acetyl groups via effects of zinc on the regulation of the PDC, that is, to the generation of acetyl groups via the tricarboxylic acid cycle , 27, or at liver . Interes++ on PDP  were reported in many maternal and fetal fluids and tissues during preeclampsia . The loccharide . Accordiccharide –64. In accharide . In factccharide . The actccharide . Along wccharide .++, Mn++, and Zn++ strengthens the response to IPG-P. This may be of importance when increased workload and adrenergic stimulation occurs, for instance, in muscle and heart cells under stress during hyperglycemia and starvation.PDP activity is strictly related to ion concentrations in mitochondria. The presence of CaCertainly, the interaction between intracellular pathways related to metabolism and vascular alterations is not fully explained yet. We argue that a large part of the pathophysiology of preeclampsia may be based on this interaction given the observation that both aspects have been described in preeclampsia and long-term alterations (higher risk of metabolic syndrome and cardiovascular disease) can certainly represent the final expression of these disrupted cross talk pathways. Whether inositol second messengers are among the key molecules in this process as it seems nowadays has been shown in detail. Many points have been already demonstrated while minor linking aspects should be investigated.Characterization of the intracellular action of IPG-P in the context of a metabolic disease like preeclampsia helps in understanding the underlying biochemical mechanisms that occur in placenta and endothelial cells. This may help in the characterization of the link between alterations reported in human placenta and the endothelial reaction that occurs in this disease. Indeed, these aspects have to be fully elucidated in human tissues of women with preeclampsia, so further studies are warranted. On the other hand, this may lead to pharmacological interventions to support and/or prevent anomalies that lead to the development of preeclampsia.