Based on the multi-parameter analysis data Portuguese honeys could be characterized by a distinctive colour, a characteristic aroma, whereas conform to the European legislation relating to honey identity and quality. Specific attention should be given in the case of heather honey which showed the highest in vitro antioxidant activity and total phenolic content. Parameters that were also highly correlated using bivariate statistics.The present study was conducted to evaluate the quality and bio-functional properties of Portuguese honeys of different botanical and geographical origins. Quality parameter analyses included the determination of palynological , physicochemical  including colour-metrics , along with volatile compounds identification using solid phase micro-extraction coupled to gas chromatography mass spectrometry. Bio-activity parameter analysis included the determination of in vitro antioxidant activity and total phenolic content using the 2,2-diphenyl-1-picryl-hydrazyl and Folin-Ciocalteu assays, respectively. Melissopalynological analysis showed that Portuguese honeys were classified as eucalyptus, chestnut and heather, recording significant variations ( Apis mellifera honeybees, has been serving as an irritator of research the last decades, since numerous studies have been published related to its quality and authenticity. The EU Council directive relating to honey  was expressed by the following equation:Preparation of DPPH Free Radical Calibration Curve. A calibration curve of concentration versus absorbance of DPPH was prepared as follows: The 1.12 × 10w/v)   and 1 mL of acetate buffer 100 mM (pH = 7.10) were placed in a cuvette and the absorbance of the [DPPH•] radical was measured at t = 0 (A0 = 0.8048).Thereafter, volumes of 1.9 mL of methanol solution of [DPPH•] concentration of 70.93 μmol/L) and the absorbance was measured every 30 min (regular time periods) until the value reached a plateau . The reaction was completed in 4 h. The absorbance of the reaction mixture was measured at 517 nm.Subsequently, 0.1 mL solution of each honey type was added to the above medium . The effective concentration of aqueous honey solutions that is the specific concentration that could decrease the [DPPH•] concentration by 50% was estimated based on the following formula:•] after the addition of honey water soluble antioxidants.The [DPPHv/v) were used as the blank sample. Reported results are the average ± standard deviation values of three replicates (n = 3).Finally, methanol and acetate buffer  were also added after 3 min. Finally, the obtained solution was filled to the mark with distilled water . This solution was left for 2 h in the dark  at room temperature and the absorbance was measured at 760 nm in a UV/VIS Spectrophotometer . Prior absorbance measurements all solutions were filtered using Whatman filters (UK) with a pore size of 0.45 μm. For quantification purposes, a calibration curve was constructed of standard gallic acid using a range of concentrations between 195–6240 mg/L:Total phenolic content of Portuguese honeys was determined in aqueous amounts of samples using the Folin-Ciocalteu colorimetric method . In a 5 n = 3).Total phenolic content was expressed as mg of gallic acid equivalents per kg (mg GAE/kg) of honey, considering the specific weight of each honey sample. Reported results are the average ± standard deviation values of three replicates (The extraction of volatile compounds found in the headspace of honey samples was accomplished using a divinyl benzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) fibre of 50/30 μm purchased by Supelco . Before analysis of samples the fibre was conditioned according to the manufacturer’s recommendations and was cleaned daily using the method of “clean” program. In particular, the injector and MS-transfer line were maintained at 260 °C and 270 °C, respectively, whereas during the “cleaning” of the fibre oven temperature was held at 80 °C for 0 min and then was increased to 270 °C at 10 °C/min (2 min hold). A split ratio of 10:1 was used.For honey sample analysis the following conditions were followed: 15 min equilibration time, 30 min sampling time, 4 mL sample volume, addition of salt and 45 °C water bath temperature. The samples  plus 20 μL of internal standard , were then placed in 15 mL screw-cap vials  equipped with PTFE/silicone septa. The vials were maintained at 45 °C in a water bath under continuous stirring at 600 rpm during the entire headspace extraction [The GC unit used in the study for the gas chromatography/mass spectrometry analysis of honey samples was an Agilent 7890A model coupled to a MS detector . The capillary column used in the analysis was DB-5MS (cross linked 5% PH ME siloxane) . Helium served as the carrier gas (purity 99.999%), at a flow rate of 1.5 mL/min. The injector and MS-transfer line were maintained at 250 °C and 270 °C, whereas during the analysis oven temperature was held at 40 °C for 3 min and then was increased to 260 °C at 8 °C/min (6 min hold). Electron impact mass spectra were recorded at 50–550 mass range and the ionization energy was 70 eV, whereas a split ratio of 1:2 was used to introduce the appropriate amount of sample on column. For the analysis of honey samples of different botanical origin, blank runs were carried out to avoid any source of contaminationIdentification and semi-quantification of honey volatile compounds assuming a response factor equal to 1.The identification of volatile compounds was achieved using the Wiley 7, NIST 2005 mass spectral library. For the calculation of Kovats indices, a mixture of n-alkanes (C8–C20) supplied by Supelco  was dissolved in n-hexane and the retention time of standards was determined according to the temperature-programmed run discussed above. Volatile compounds having ≥80% similarity with Wiley library were tentatively identified using GC-MS spectra. The method of identification was based on the combination of MS data found in Wiley 7 NIST 2005 mass spectral library and data of Kovats index values that were determined for each volatile compound and then compared with those included in the Wiley MS library.For the semi-quantification analysis the internal standard method was used. Data were expressed as concentration  based on the ratio of peak areas of the isolated volatile metabolites to that of the internal’s standard, multiplied by the final concentration of the internal standard (1 mg/L), assuming a response factor (RF) equal to 1 for all the compounds . Data wep < 0.05) according to botanical origin . Furthermore, in order to evaluate the effect of geographical origin on physicochemical and bioactivity parameter values, especially in the case of eucalyptus and chestnut honeys, in which samples originated from different regions, T-test was applied (p < 0.05). Correlations were obtained by Pearson’s correlation coefficient (r), at the confidence level p < 0.05. All data processing was performed using the SPSS v.20.0 statistics software .Data of honey samples were subjected to analysis of variance (ANOVA) in order to show any statistical differences , Castanea sativa Mill. (samples G5 and G6) and Erica spp. (sample G8) pollen grains at a percentage of >45%. Therefore, these pollen grains were the dominant ones. The presence of secondary (16–45%), minor (3–15%) and identified (<3%) pollen was also confirmed  from six districts in Portugal  Pires et al. [Erica spp. pollen grains per sample varied between 45% and 71%, with an average ± standard deviation value equal to 56 ± 9%. Heather honey from Trás-Os-Montes region in Portugal showed an average value of Erica spp. pollen grains ca. 60 ± 1% [Castanea sativa Mill. pollen grains among Erica spp. honeys was also reported by the authors, in agreement with the results of the present study  in total sugar content among eucalyptus and chestnut honeys of different geographical origin  recorded the higher value in chestnut honey from Bragança, in Vinhais County. In all honey samples analysed total sugars recorded values higher than 80% (g/100 g). There were observed significant differences (l origin . The prep < 0.05) were observed among honey types of different botanical and geographical origin in the moisture content. Moisture content of Portuguese honeys ranged between 15.23 ± 0.15 to 17.93 ± 0.06. The lowest value was recorded for chestnut honey from Bragança region and the highest value was recorded for eucalyptus honey from Esposende region. In total, moisture content values are in accordance with the EU council directive relating to honey [Erica spp.  in which the moisture upper limit may be 23%. From a scientific point of view, the determination of moisture is related to honey preservation and storage, as high water content can lead to the growth of moulds, that may alter a product’s flavour and shelf-life [In addition, significant differences  between samples  according to Portuguese honey botanical and geographical origin. On the other hand, salinity is a measure of the saltiness or dissolved salt content in an aqueous medium. For instance, chestnut honeys recorded the highest salinity values (g/L) followed by heather and eucalyptus honeys.Total dissolved solids reflect all inorganic and organic molecules that are present in honey in molecular, ionized or micro-granular  suspended forms . TDS recTo the best of our knowledge, data on TDS and salinity contents have never been reported before for Portuguese honeys. Available data in the literature originate from Algerian, Greek, Cypriot and Egyptian floral honeys ,34, in wEucalyptus spp. honeys purchased from local markets in Portugal.Free acidity of honey is owed to its organic acid content in terms of gluconic, formic, malic, succinic, oxalic, butyric, citric, 2,3-dihydroxybutanedioic, pyroglutamic, lactic, benzoic, maleic, isobutyric, pyruvic, α-ketoglutaric and glycolic acids. Despite the fact that organic acids are found in minor proportions in honey (0.17–1.17 g/100 g), these play an important role in the developed aroma and flavour of honey, since the majority of the aforementioned acids are present in honey in the form of volatile esters. On the other hand, storage temperature, processing conditions and the nectar source may influence organic acid content of honey. In addition, an increased acidity may serve as an indicator of honey fermentation and transformation of alcohol into organic acid . The freVitamin C recorded the highest value (mg/100 g) in heather honey. Even though honey is not a rich source of vitamin C compared to fruits like orange, lemon and so forth, hence, vitamin C contributes to the total antioxidant activity of honey and more specifically to that of the water soluble antioxidants that are present . Previoua* values) and yellow components  (pigments) were present in all honey samples analysed in conformity with the aforementioned work [p < 0.05) according to honey geographical origin. Comparing the chromaticity values of eucalyptus, chestnut and heather honeys, only L* and b* values varied significantly (p < 0.05) according to honey botanical origin.In ned work . What isp < 0.05) among honey samples of different botanical origin. The highest values were recorded for eucalyptus honeys followed by chestnut and heather honeys.The difference or distance between colour parameters (ΔΕ* or ΔΕab*) is a metric of interest in colour science. The determination is normally based in the Euclidean distance and it allows a “quantified” theory of an aspect that could only be described with single values. It is a critical measure in the colour science and may define how colour travels in an independent multi-dimensional space. The ΔE* determination might be of interest since the human eye is more sensitive to certain colours than others. Results showed that ΔΕ* values recorded significant differences (p < 0.05) with respect to botanical and geographical origin.The U.S. Department of Agriculture has classified honey into seven colour categories according to its colour: water white, extra white, white, extra light amber, light amber, amber and dark amber. The Pfund colour scale may provide an accurate, inexpensive and convenient methodology for measuring colour intensity of honey as a distance (in mm) in the chromatic space. Respective values (in mm) are: <9 for water white, 9–17 for extra white, 18–34 for white, 35–50 extra light amber, light amber 51–85, amber 86–114 and dark amber > 114 . PortuguFerreira et al.  charactep < 0.05).Colour intensity, defined as the difference in the absorbance at 450–720 nm, may give information about the presence of pigments  in honey. It has been reported in the literature that dark coloured honeys usually have higher colour intensity values ,28,33. ISpectrometric assays like DPPH and Folin-Ciocalteu may be routinely used for the in vitro characterization of honey bio-functional properties. The DPPH assay evaluates the antioxidant activity of a sample. The free radical can be neutralized either by direct reduction (via electron transfer) or by radical quenching (via H atom transfer) . It has In general Portuguese honey samples showed a higher in vitro antioxidant activity compared to Polish lime, nectar-honeydew, rape, honeydew, acacia and buckwheat honeys . Greek pAnother important issue to discuss is that the antioxidant activity not only depends on the botanical origin of honey but also on the geographical origin . ParametThe method of Folin-Ciocalteu is largely used to evaluate total phenolic content despite the arising interferences of this assay since the reagent mixture (phosphotungstic acid and phosphomolybdic acid) also reacts with other non-phenolic reducing compounds  and affects absorbance measurements, therefore leading to an overestimation of the phenolic content . HoweverThe lowest TPC content was recorded for eucalyptus honey from Esposende region (Braga) (ca. 422 mg GAE/kg), while the highest phenolic content (ca. 1418 mg GAE/kg) was found in chestnut honey from Vinhais region (Braganca), followed by heather honey (ca. 1380 mg GAE/kg) from Vila Nova de Ceira region (Coimbra) being much higher than the results reported for total phenolic content of heather honey (ca. 500 mg GAE/kg) from Boticas region in Portugal . Some otBut what is the main reason for such fluctuations? At first, the analytical instrumentation and methodology have definitely a significant effect on the quantification of such compounds. At the same time and in a greater extent, climatic and soil conditions may fully describe such phenomena. Bees collect pollen from different plants grown in different regions. Pollen is a good source of numerous phytochemicals. In that sense, polyphenols and other bio-functional compounds are transferred to honey through pollen, which can justify the observed fluctuations in TPC content among honey samples of different botanical and geographical origins .Salmonella, etc.) along with its wound healing boosters should be considered in its overall bio-functionality [Finally, the antimicrobial activity of honey against a wide range of microbial contaminants  was used at the confidence level p < 0.05. In particular, a slight positive but insignificant correlation  was obtained for pH and vitamin C content values. This was also the case for free acidity and pH values of Portuguese honeys . Total colour difference (ΔΕ*) of honey samples using the CIELAB system was negatively but significantly, correlated with the Pfund scale colour determination . To our knowledge, there are limited studies upon such correlations.Despite the limited honey samples analysed, there were collected some important data regarding physico-chemical, palynological and bioactivity parameter values correlations that could be indicative of the specific Portuguese honeys analysed. The bivariate Pearson’s correlation ; slightly positively correlated with Pfund scale measurements ; and positively correlated with colour intensity measurements . For the chestnut honeys respective correlations were r = −1 (p = 0.01), r = 1 (p = 0.01), and r = 1 (p = 0.01). As it can be observed the correlations obtained between colour parameter analyses and pollen grain percentages for chestnut honeys were more promising.Regarding the correlation between pollen grain percentages and colour parameters some important findings were also observed. In the case of eucalyptus honeys, pollen grains were negatively correlated with ΔE* values . In addition, there was also a strong positive correlation between total phenolic content and colour intensity values . Such findings are in accordance with previous works in the literature upon this theory [r = 0.975, p = 0.000).Finally, for bio-activity parameter values more positive results were obtained. Total phenolic content was strongly correlated with the in vitro antioxidant activity  by honey botanical  on physicochemical and bio-functional activity parameters. Colour-metrics revealed that colour of Portuguese eucalyptus, chestnut and heather honeys could be defined as light-amber to amber with yellow and green components . Heather honey showed the higher in vitro antioxidant activity, total phenolic and vitamin C contents. The aroma of honeys was affected by botanical and geographical origin and was the outcome of the synergistic action of plenty volatile compounds. In addition, some important correlations among physico-chemical, palynological and bio-functional activity parameters were obtained, enhancing further the identity of Portuguese honeys. Present data support the literature on Portuguese honeys and may be used by different agencies in studies/research related to characterization, authentication and adulteration control of Portuguese honey.Results of the present study showed that both botanical and geographical origin of Portuguese honeys had a significant impact (


This preliminary study aimed to examine the feasibility of sentinel lymph node biopsy (SLNB) using contrast-enhanced ultrasound (CEUS) vs. indocyanine green fluorescence (ICG), combined with blue dye in patients with breast cancer.This was a retrospective study of consecutive female patients with invasive stage I-III  primary breast cancer at the Peking Union Medical College Hospital between 01/2013 and 01/2015 who underwent preoperative SLNB by ICG + blue dye or CEUS + blue dye. The numbers of detected SLNs, detection rates, and recurrence-free survival (RFS) rates were compared between the two groups.P = 0.814). The average numbers of SLNs detected per patient showed no significant difference between the two groups . After a median follow-up of 46 months, five patients in the CEUS + blue dye group and 15 in the ICG + blue dye group had recurrence. RFS rates showed no significant difference (P = 0.55).A total of 443 patients were included. The detection rates of SLNs in the CEUS + blue dye and ICG + blue dye groups were 98.4 and 98.1%, respectively (This preliminary study suggests that CEUS + blue dye and ICG + blue dye are both feasible for SLN detection in breast cancer. Breast cancer is currently the most common malignancy in Chinese women , 2. ReceThe current standard SLNB method involves the injection of a technetium-labeled nanocolloid and blue dye interstitially into the breast, either around the tumor via the periareolar procedure . Use of In China, using blue dye alone is common in SLNB. Although SLNs are dyed, blue dye cannot indicate their localization prior to skin incision. As a result, the identification rate is not as high as that of the dual method (radiotracer and blue dye) , 8. TherTherefore, new techniques are being developed for SLNB. Among them, indocyanine green fluorescence (ICG) and contrast-enhanced ultrasound (CEUS) have some advantages , 6, 9–21Therefore, the aim of the present preliminary study was to examine the effectiveness of SLN identification using CEUS vs. ICG, in combination with blue dye. In addition, we attempted to compare breast cancer recurrence rates between both techniques. The present results provide a proof-of-concept for designing prospective trials.This study was approved by the independent ethical committee/institutional review board of Peking Union Medical College Hospital (PUMCH). We obtained permission from PUMCH to collect data from the Breast Surgery Department Database. As this was a retrospective study of anonymized data without any contact with the patients, individual consent was not required. The study was performed in accordance with the relevant guidelines and regulations.A retrospective review of the Breast Surgery Department database of PUMCH was performed. Consecutive female patients aged ≥18 years, with invasive primary breast cancer , who underwent preoperative SLNB using ICG or CEUS combined with blue dye between January 2013 and January 2015 were included for analysis. Preoperatively, these patients had no clinical  or radiological signs of lymph node invasion. Patients who received neoadjuvant systemic therapy (including chemotherapy and endocrine therapy) were excluded, as well as those with bilateral breast cancer or a history of axillary surgery. All eligible patients in the database had complete medical information. No patient was lost to follow-up. Follow-up was censored on January 19, 2018.The choice of the SLNB procedure was based on the surgeon’s experience and preference at the time of surgery. All SLNB procedures were performed by the same team of senior and skilled breast surgeons. Undiluted methylene blue  was used for both SLNB procedures.For ICG + blue dye, ICG  was first dissolved in 5.0 ml sterile water (5.0 mg/ml stock solution). Then, 1.25 ml of the stock solution was diluted in 5.0 ml sterile water for injection (1.0 mg/ml). Before surgery, 0.2 ml of methylene blue (10 mg/ml) and 0.2 ml of ICG (1.0 mg/ml) were injected intradermally into the periareolar region. The breast was gently massaged for 5 min. Next, the lights were turned off and a photodynamic eye (PDE) camera  was used to trace the lymphatic flow. The location of the skin incision for the SLNB was selected as the point where the fluorescent signal disappeared  with 18L6HD and 9 L4 high-frequency linear array probes, using contrast pulse sequences (CPS). Low mechanical index (MI) values were used (MI = 0.06) to reduce cavitation and microbubble destruction. Sonovue  was used as the contrast agent. The Sonovue powder was mixed with 2.0 ml of sterile saline. The ultrasound contrast agent (0.4 ml) was injected intradermally into the periareolar area, and the injection area was gently massaged for 10-30 s. Subcutaneous lymphatic channels could be visualized immediately on CPS. Enhanced lymph nodes were detected by moving the probe along the channels .The detection rate of SLNs was defined as the number of patients with SLNs identified by the labeling technique divided by the total number of patients administered the technique. Categorical data were compared by the two-tailed chi-square test. Quantitative data were compared by Student’s t-test. Recurrence-free survival (RFS) was estimated by the Kaplan-Meier method. A two-sided log-rank test for time-to-event endpoint was used. Differences were considered statistically significant at P > 0.05). There were also no significant differences between the two groups in tumor size, tumor grade, stage, lymphovascular invasion, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) . No adverse reactions or complications related to the ICG procedure, microbubbles, or blue dye injection were recorded.Between January 2013 and January 2015, a total of 443 patients were operated and included in this study. The ICG + blue dye technique was used in 316 (71.3%) individuals, and CEUS + blue dye in 127 (28.7%) patients. Table P = 0.814). The numbers of SLNs identified showed no significant difference between the two groups . There were no significant differences in the positive SLN rate between the two groups. Precisely, there were 13 (10.2%) patients  with positive SLNs in the CEUS + blue dye group, and 36 (11.4%)  in the ICG + blue dye group (P = 0.726) . Of the 316 patients administered ICG + blue dye, SLN detection was successful in 310 (98.1%). The SLN detection rate showed no significant difference (P = 0.105)  in the CEUS + blue dye group, and 5  in the ICG + blue dye group.P = 0.55)  months. Among the 443 patients, 20 (4.5%) had tumor recurrence. Five (3.9%) individuals in the CEUS + blue dye group had recurrence, including 1, 2 and 2 with axillary recurrence, ipsilateral breast/chest wall recurrence and bone metastasis, respectively. A total of 15 (4.7%) patients in the ICG + blue dye group showed recurrence, including 3, 4, 4 and 4 with axillary recurrence, ipsilateral breast/chest wall recurrence, bone metastasis and lung metastasis, respectively. The 3-year RFS was 95.6% in the CEUS + blue dye group versus 94.3% in the ICG + blue dye group  had 0/3 and 0/4 positive SLN, respectively; the third patient, a 38-year old woman, had 1/4 positive SLN for a macrometastasis and underwent ALND, with 0/18 positive lymph node.ICG, a novel technique for SLNB, is increasingly used in clinical practice. The SLNB detection rate with ICG alone ranges from 93.1 to 100%, for 1.5-5.4 sentinel lymph nodes sampled per patient , 20, 21.CEUS is another new technique for SLNB and has been validated in a pig melanoma model , 26. SubIn the present preliminary study, the detection rates of SLNs for the two techniques were high and comparable: 98.4% for CEUS + blue dye, and 98.1% for ICG + blue dye. These rates are similar to that (96%) reported in the literature , 28. TheWithout performing ALND in all patients, the real false-negative rate could not be determined, but the rate of ipsilateral axillary recurrence could be used as an imperfect adjunct. In the present study, the recurrence rates in the ipsilateral axilla were low [1/127 (0.8%) and 3/316 (1.0%)], suggesting that false-negative rates for both approaches were most likely low. The reported false-negative rate for SLNB is 5-13%, depending upon the number of SLNs sampled, the SLNB method applied, and the cancer type , 30. In In addition to axillary recurrence cases, six (1.4%) patients had ipsilateral breast/chest wall recurrence and 10 (2.3%) developed distant metastasis during the 46-month follow-up. These rates were similar to those reported previously –35. HoweThis study had limitations. ALND was not performed in all patients, and the false-negative rates of the two novel techniques could not be evaluated. Even though there were no significant differences in baseline patient and tumor characteristics between the two groups, a retrospective analysis inevitably has some biases, e.g. we were limited to the data available in medical charts. Furthermore, the surgeons were free to select the preferred method for different patients, and the exact reasons for method selection were usually not indicated in patient charts. Finally, patients assessed by the radiotracer + blue dye technique could not be included because our center does not use radiotracers.Overall, the present preliminary study suggested that CEUS + blue dye and ICG + blue dye are both feasible techniques for SLNB in breast cancer. Randomized controlled trials including the radiotracer + blue dye gold standard technique are required to confirm the feasibility, efficacy, and safety of these two novel techniques before their introduction into mainstream clinical practice.


Background: This study aims to assess lead exposure and associated risk factors among newly arrived migrant (M) (immigrant and refugees) children in Greece and a matched control of native (N) children. Methods: A prospective, cross-sectional study was performed in an outpatient clinic of a tertiary children’s hospital. Results: From 2010 to 2014, 598 children (M/N: 349/249) with a mean age of 6.96 years old  were enrolled. Blood lead levels (BLLs) ranged from 0.7 to 21 μg/dL in migrant and from 0.4 to 10 μg/dL in native Greek children. Elevated BLLs ≥ 5 μg/dL were detected in 27.7% of migrants and 1.2% of natives (p < 0.001). A significant association was found between EBLLs and childrens’ age (≤5 years)  and EBLLs with Asian origin . Conclusion: New migrant children presented with increased BLLs when compared to their age- and sex-matched controls. Younger age and Asian origin were significant risk factors associated with elevated BLLs among children. Early screening, secondary prevention, and regular follow-up could prove useful in this vulnerable population. Lead exposure and poisoning remains a preventable health issue for millions of children worldwide. There is sufficient evidence that lead exposure is associated with various long-term, adverse health outcomes, so several health organizations have issued prevention guidelines . HoweverThe sources of lead contamination vary between developed ,5 and deIncreased BLLs are more prevalent in immigrant and refugee children, which is interrelated to a number of contributing factors, such as exposure in their native country or during their journey of transition, as well as specific cultural habits or housing conditions that may persist in receptive countries . AdditioFor over two decades, Greece has been facing an increased inflow of migrants, initially economic immigrants from Eastern European countries and recently refugees, mainly originating from the Middle East. According to the most recent Population and Housing Census data, the number of documented immigrants was calculated at 8.4% of the country’s total population . The MinConsidering the large influx of migrants in Greece and their possible lead exposure, it is important to identify the frequency and levels of lead exposure in the newly arriving pediatric population in order to create prevention strategies and policies.The aim of the present study was to assess the prevalence of lead exposure among a population of migrant children, newly arrived in Greece, and compare this to a group of matched controls. A secondary objective was to identify possible risk factors associated with lead exposure in the group of migrants. In this prospective cross-sectional study, all migrant children between 1 and 14 years old, examined in a special outpatient clinic at “P. & A. Kyriakou” Children’s Hospital, within three months of their arrival in Greece, between May 2010 and March 2014 were enrolled in the study. The above population consisted of immigrant and refugee children who were either self-referred to obtain a green card (immigrants) or referred by non-governmental organizations for health status assessment before placement in shelters (refugees). Informed consent was obtained from all participants’ parents or guardians. The Institution Review Board of “P. & A. Kyriakou” Children’s Hospital approved the study protocol.The guardians of all eligible children were informed of the study objectives and were interviewed in person using a structured questionnaire including sociodemographic data, past medical history, and date of entry in the country. Available medical, as well as travel documents, were also accessed. Interpreters were involved when necessary to achieve the best communication with children and parents. Children younger than 12 months or older than 14 years old, those unaccompanied, and those having entered the country for more than 3 months, were excluded. All children underwent a complete physical examination, including anthropometric measurements and growth assessment. Additionally, a group of healthy native children, attending as outpatients of the endocrinology, ophthalmology, and surgical departments of our hospital, matched by age and gender, were enrolled in the study as controls. Informed consent was obtained from all participants’ parents or guardians. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Institution Review Board of “P. & A. Kyriakou” Children’s Hospital (Reference number 145/19/05/10).4) 2HPO4 (2%)) using an Agilent 7500s-Agilent instrument with autosampler Cetas ASX 500 . The lower limit for detection of lead in blood was 0.03 μg/dL and that of quantitation was at 0.1 μg/dL.Blood analysis with full blood count and ferritin serum levels was performed. The blood samples for measurement of BLLs were collected in ethylenediaminetetraasetic acid (EDTA) tubes, and stored at 4–6 °C in order to be used at a further stage. BLLs were measured by inductively coupled plasma–mass spectrometry (ICP-MS) following a 20-fold dilution with alkaline solution (concentrated nitric acid (2%), Triton X-100 (5%), and  . Low serIron supplements were provided to all children with anemia or iron deficiency. Additionally, all immigrant and refugee children were provided with leaflets issued in their native language that included nutritional advice, information on lead poisoning effects, potential sources of contamination, and instructions on how to prevent exposure.The term “immigrants” (I), was used to describe children whose parents had a long-term residence permit, conforming to the terms of the International Organization for Migration (IOM) in the Glossary of Migration. The term “refugee” (R) was used to describe minors unable to return to their home country due to war or conflict, asylum seekers, and irregular entrants. Both immigrants and refugees were defined as “migrants” (M) .2 test (or Fisher’s test) was used. p < 0.05 was considered to indicate statistical significance. Children were distributed by immigrant or refugee status according to their demographic characteristics and medical history. The binary values of the BLLs (levels ≥5 μg/dL vs. <5 μg/dL) were used as the main endpoint of the analysis. The non-parametric Mann–Whitney and Kruskal–Wallis test was used for continuous variables, due to asymmetric data distributions, while for the categorical variables, the χMultivariate logistic regression models were used to explore the risk factors of the EBLL occurrence. Τhe association between the child’s status (migrants versus native population) with the main health indicators: anemia (yes versus no) and ΕBLL (yes versus no) were investigated. The statistical analyses were conducted using the SPSS statistical package .n) children were enrolled from May 2010 to March 2014. Two refugee children were subsequently excluded due to an incomplete evaluation of their health status. p = 0.041) presented with anemia, and 17.5% and 6.4%, respectively, were iron-deficient (p ≤ 0.0001). A total of 351 migrant (190 refugees and 161 immigrants) and 249 native (BLLs in both groups ranged from 0.7 to 21.03 μg/dL (0.7–21 μg/dL in migrants and 0.4–10 μg/dL in natives), and mean values of BLLs of all children (both natives and migrants) were 2.9 ± 2.4 μg/dL, with a median of 2.2 (0.4–21) μg/dL. Among migrant children, those belonging to the immigrant subgroup had mean BLLs of 4.3 μg/dL and a median of 3.7 μg/dL; the refugee mean was 3.8 μg/dL, and the median was 3.4 μg/dL. In contrary to those, mean BLLs found in the native participants was 1.3 μg/dL (median: 1.1 μg/dL). Moreover, the mean age of all children with EBLLs was 4.89 ± 2.26 years (range 12 months–14 years).p-value ≤ 0.0001). Among migrant children with EBLLs, the majority (93.8%) presented lead levels between 5 and 10 μg/dL. A percentage of 6.2% presented with EBLLs >10 μg/dL (max 21.3 μg/dL). In contrast, only three children from the group of natives showed EBLLs . Interestingly, lead exposure prevalence was slightly higher in immigrant children (32.3%) as compared to refugees (25 %), p = 0.05.In n = 90, 93.8%), mainly from Afghanistan (44.4%) and Bangladesh (23.3%), while the rest were newcomers from Pakistan (17.8%), India (8.9%), Syria (2.2%), China (1.1%), Philippines (1.1%), or Iran (1.1%). Children from Africa originated from Egypt (2.1%), Morocco (1.05%), and DR Congo (1.05%), while those from Europe were migrants from Albania and Georgia (1.05%).The vast majority of migrant children with EBLLs originated from Asia  and the geographic area of origin , p-value 0.023). The association of migration status with EBLLs was of marginal statistical significance , p-value 0.057). Univariate analysis showed that immigration status as independent risk factor was not associated with EBLLs . Although a relation between anemia, iron depletion, and EBLLs was identified following multiple logistic regression, these variables were not statistically significant . A logistic regression analysis of the possible risk factors associated with EBLLs is presented in The present study is the first to provide evidence of BLLs in newly arriving migrant children in Athens, Greece. Overall, 27.7% of new migrant children presented laboratory evidence of lead exposure, significantly higher than native children (1.2%), while in 6.2% of them BLLs exceeded levels of 10 μg/dL. A younger age and being of Asian origin were identified as significant risk factors for elevated BLLs in our study group. Assessment of lead exposure upon arrival of migrant children and subsequently after their resettlement in the host country to identify ongoing exposure should be considered as a public health priority since children at risk show no clinical signs and are only identified during screening.BLLs in new migrant participants were significantly higher than those measured in the native population. This is in accordance with data from the United States ,19,20, Cp-value 0.041) in the Fisher’s exact test, but this was not statistically significant following multivariate analysis. These results are in accordance with previous studies that found no correlation between BLLs and anemia [Anemia and iron deficiency were common findings among children with lead exposure. Lead impairs heme synthesis and increases red blood cell destruction, causing anemia . EBLLs, d anemia ,24,25. Md anemia , while od anemia ,28. Irond anemia ,29.Multivariate analysis revealed younger age and geographic area of origin as significant risk factors for EBLLs, whereas migration status was only marginally associated. Children 1–5 years old were more likely to have increased levels of lead. We assume that younger children were more susceptible to lead exposure due to hand-to-mouth behavior that may lead to increased exposure in a lead-abundant environment . There iThe highest BLLs were detected in children originating from Asia, particularly from South Central Asia, namely Afghanistan and Bangladesh. In a sample of 1406 refugee children screened for BLLs in Washington, USA, (2013–2014), those from Afghanistan (50%) presented higher percentage of EBLLs (≥5 µg/dL), compared to those from Somalia (15%), Burma (16%), and Iraq (11%). This was related to the exclusive use of leaded gasoline . SimilarBoth immigrant and refugee children are described as a population at risk for EBLLs. Possible explanations include environmental exposure, living conditions, eating habits, parental occupation, socio-economic status, cosmetic use, and (mouth and hand) hygiene behavior in the country of origin ,9. It mun = 15).This study has some limitations. The reported results are restricted to a subpopulation of immigrants and refugees arriving in Athens and, therefore, must be interpreted accordingly. Additionally, the fact that unaccompanied refugee children, not able to provide informed consent, were excluded from our study might affect the overall estimates, as this group may be more susceptible to lead exposure. It must be noted though that at that time their number was small (Furthermore, due to language barriers, we lack detailed records with regard to additional factors possibly related to EBLLs in migrants, so we could not investigate respective associations on the reported difference of BLLs between the group of migrant and native children. Our study population was chosen to evaluate solely newly arrived migrant children to collect baseline information. Thus, we were unable to assess the possibility of continued lead exposure due to personal habits or living conditions after migration, which could be an essential factor for ongoing exposure and harm to those children residing in Greece for extended periods of time. Finally, the gender-distribution among the two groups of native versus migrant children is different with more girls among the subgroup of Greek children. Girls are generally known to experience lower lead exposure, so this discrepancy presumably exaggerates the BLL difference between the two groups. Despite the above limitations, the study has some strong points. It is the first study to document the laboratory evidence of lead exposure and certain associated risk factors in a subpopulation of new immigrant and refugee children arriving in Greece. Since the prevention of lead exposure in children is essential considering its possibly irreversible effects, if present, and the fact that there are no “safe” blood levels, our findings can guide the development of effective prevention strategies addressing this vulnerable population.We found that a considerable proportion of newly arriving migrant children in Greece present laboratory evidence of lead exposure that is significantly higher than their native counterparts. A younger age and being of Asian origin were significant risk factors for EBLLs. Screening of all migrant children soon after their arrival, especially the youngest ones and those originated from South Central Asia, appears essential. Additional data regarding lead exposure of migrant children upon arrival and after resettlement from host countries in Europe are necessary to provide evidence-based screening recommendations. Early screening, secondary prevention, and regular follow-up could prove useful in this vulnerable population.


Obesity and chronic pain are common comorbidities and adversely influence each other. Advanced age is associated with more comorbidities and multi-morbidities. In this study, we investigated the burden of overweight/obesity and its comorbidities and their associations with chronic pain in a random population sample of Swedish older adults.N = 6243). Data were collected from a postal questionnaire that addressed pain aspects, body mass index (BMI), and health experiences. Chronic pain was defined as pain during the previous three months. According to the 0–10 Numeric Rating Scale, pain scored ≥7 corresponds to severe pain. Binary logistic regression was used to determine the variables associated to pain aspects.The cross-sectional analysis involved a random sample of a population ≥ 65 years in south-eastern Sweden (2) experienced chronic pain (58%) than those who were low-normal weight  or overweight . Obese elderly more frequently had pain in extremities and lower back than their peers. In the multivariate model, obesity (Odds Ratio (OR) 1.59, 95% Confidence Interval (CI) 1.33–1.91) but not overweight  was associated with chronic pain. Obesity  was also significantly related to severe pain. We also found other comorbidities – i.e., traumatic history , rheumatic diseases , age ≥ 85 years , and depression or anxiety diagnosis  – showed stronger associations with pain aspects than weight status. Conclusion: In older adults, excess weight (BMI 30 or above) is a potentially modifiable factor but not the only risk factor that is associated with chronic pain and severe pain. Future studies should investigate the effectiveness of interventions that treat comorbid pain and obesity in older adults.A total of 2633 (42%) reported chronic pain. More obese older adults (BMI ≥30 kg/m Chronic pain is common in older adults, but the prevalence varies widely, ranging from 20 to 93% . This wiThe prevalence of overweight and obesity in the elderly population is increasing worldwide , 5. ExceObesity and chronic pain often occur simultaneously. The two conditions adversely influence each other , 11. BotObesity and chronic pain share some co-morbidities  , 21–23 aUsing a cross-sectional postal questionnaire, this study collected data from a stratified random sample of 10,000 older adults (≥ 65 years old) based on five age strata  from the Swedish Total Population Register for the two largest cities (Linköping and Norrköping) of a county (Östergötland) in south-eastern Sweden. The questionnaire was mailed in October 2012 and, if needed, two reminders at two-week intervals were mailed. The collection of questionnaires closed in January 2013.The survey included several validated instruments/scales. An overview of all parts of the survey has been presented elsewhere , 35. TheAge, sex, educational level, and civil status were recorded from the respondents’ answers in the postal survey. Civil status was categorized as single, married, divorced, and widowed. Educational level was classified as high school (elementary/secondary), upper school, or vocational training for more than two years, college or university for one to two years, and college or university for three years or more.2) was calculated using these data. Specifically, BMI was calculated as weight (kg)/height (m)2 and classified according to the criteria developed by the World Health Organization (WHO): < 18.5 = underweight; 18.5–24.9 = normal range; 25.0–29.9 = overweight; and ≥ 30.0 = obesity. Morbid obesity (severely obese) is defined as a BMI category above 35.0.Height and weight were recorded from the respondents’ answers in the postal survey and the BMI (kg/mr = 0.89 to 0.97 for different age groups and gender) [Several studies have compared the validity of measured weight- and height-calculated BMI and self-reported weight- and height-calculated BMI. High correlations were reported between the two measures (Pearson’s  gender) . Compare gender) .Pain intensity over the preceding seven days was assessed using an 11-point numeric rating scale (NRS), ranging from 0 (no pain) to 10 (worst imaginable pain) . The cutAll the respondents marked their painful site for the previous seven days on a body manikin divided into a total of 45 sections on the front and on the back , 45. FroThe evaluation of co-morbidities was based on a 12-item self-reported list covering different aspects of common co-morbidities: (1) traumatic accident, (2) rheumatic arthritis and osteoarthritis, (3) cardiovascular diseases , (4) diseases of airways or lungs, (5) low mood and depression, (6) anxiety, (7) diseases of the gastrointestinal system, (8) diseases of the nervous system, including eyes and ears, (9) diseases of the urogenital organs, (10) diseases of the skin, (11) tumours and cancer, and (12) metabolic diseases such as diabetes, obesity, anorexia, bulimia, and goitre. These co-morbidities were reported on a five-point scale: 1 = no; 2 = yes, according to both my own and my doctor’s opinions; 3 = yes, according to my own opinion; 4 = yes, according to my doctor’s opinion; and 5 = do not know. We combined the answers for 2 and 4 to increase the robustness of measurements of the presence of a certain comorbidity. Hence, these items were dichotomized as follows: yes, according to both my own and my doctor’s opinions plus according to my doctor’s opinion and the three other alternatives.Hälsokurvan) [From the instrument “Health Curve” (okurvan) , we chosokurvan) ; a scorep-value < 0.05 was considered statistically significant. Binary logistic regression was used to test predictors for chronic pain, moderate pain (NRS 4–6), and severe chronic pain (NRS 7–10). BMI was entered as a categorical predictor using low-normal weight as the reference group. In the univariate analysis, we examined the effect of each variable on chronic pain, including demographic aspects (age and sex), social economic factors , lifestyle habits , and obesity or pain-related comorbidities. In the multivariate logistic regression, a forward  method was used by entering each variable forwardly and removing the least significant variables from the model until all remaining variables were significant . Goodness of fit was performed using the Hosmer and Lemeshow test where a p-value greater than 0.05 indicated good fit of the model. Collinearity was tested using a correlation matrix of estimates. Because diagnosis of depression and anxiety showed a high collinearity (r = 0.608), we transformed the two variables to a new variable (1 = depression and/or anxiety) and re-tested the correlations. This new variable represents aspects of mental health.Statistical analysis was performed using the SPSS statistical package . Data were reported as the mean with standard deviation (SD), the median with interquartile range (IQR), or the number with percentage based on the data distributions. Missing data were excluded from the analysis and calculated percentages were obtained from the number of valid responses. Differences among groups were assessed using the Chi-square, the one-way ANOVA, and the Kruskal-Wallis tests as appropriate. A 2 and 39% (2434) were categorized as overweight and 14% (871) were categorized as obese. In the obesity group, 17.3% (151) were categorized as morbidly obese. Compared with the low-normal weight and the overweight groups, the obesity group was relatively younger (< 75 years old), had a higher proportion of males, lower education, lower yearly income, more smokers, and more suspected high alcohol consumers . Among the individuals with chronic pain, 32.7% of the obese group, 23.5% of the overweight and 20.6 of the low-normal weight (reported severe pain (p < 0.001). Similarly, according to NPS, the spread of chronic pain was more evident in the obese group (median = 4) than in the two other groups (median 3 for both groups) (p < 0.001). Pain in extremities and lower back were also more prevalent in the obese group  but not overweight  was more likely associated with chronic pain than low-normal weight. Some factors, such as having trauma or injury accident history  and rheumatic diseases , showed higher associations with chronic pain than obesity status.Univariate logistic regression showed that higher BMI, being female, low education (nine-year compulsory school), smoking history, high alcohol consumption, and several comorbidities were positively associated with chronic pain Table . Most ofp < 0.05, Table p < 0.01). However, aged 85 and over  and depression and/or anxiety diseases  were more strongly linked to severe pain than being obese. Sociodemographic factors such as age, gender, education, and income levels were also significantly related to having moderate pain. Being an ex-smoker, certain co-morbidities , and number of pain sites were also significant regressors of severe pain.Within the chronic pain group, obesity and overweight were weakly but significantly associated with moderate pain  of chronic pain that have a greater impact than obesity. In the logistic regressions, we found that other obesity-related diseases/co-morbidities – e.g., obstructive sleep apnoea (categorized as a respiratory disease), gallbladder disorder , stroke , diabetes (categorized as a metabolic disease), and mental illness (depression or anxiety) – exhibited a modest association with chronic pain. These impacts may have been stronger if these diseases/co-morbidities had been asked for specifically and not included in broader categories as in the present study. Therefore, in an aging population with a high prevalence of multiple morbidities, we need to consider the above common comorbidities when evaluating chronic pain and suffering. In addition, these comorbidities are not the same comorbidities younger people experiece when suffering from chronic pain. For example, unlike a chronic pain study of younger people , two comThe analysis of these factors together with weight status provides a subset of the aging population who may be more likely to have chronic pain. To meet the particular needs of pain management for older people  , health One important limitation of this cross-sectional study was the bias from self-reported anthropometric measures. Despite a high correlation between self-reported and measured values, the underestimation of excess weight by self-reported values has been reported , 37. If Another weakness of our study could be the lack of generalizability of the results due to the rate of non-participants in the study population, with a valid response of 62.7%  . The nonIn addition, our cross-sectional analysis did not uncover any causation. We cannot identify a direct cause-and-effect relationship between these factors. The results should be tested longitudinally in future studies. Additionally, although many important co-variates were included in the regression analysis, some potentially meaningful co-variates such as dietary intake and physical activity were not collected in this study. Previous studies demonstrated that unhealthy excess food intake and sedentary living cause weight gain and systemic inflammation , 69. To Chronic pain affects more obese older adults than their low-normal or overweight peers. Excess weight (BMI 30 or above) is a potentially modifiable factor but not the only risk factor that is associated with chronic pain and severe pain. It is important for healthcare professionals to understand the multiple factors involved in the complex relationship between pain and excess weight. Healthcare professionals and policy makers should address the management of the coexisting modifiable factors instead of focusing on a single achievement . Future research should investigate the effectiveness of interventions that treat comorbid pain and obesity in older adults.


Studies focusing on accuracy of intraoral digital models in the palatal region are scarce. The present study aimed to investigate the influence of different scanning sequences on palatal trueness and to assess deviation and distribution character of trueness in palate.Overall, 35 participants accepted three types of procedures to acquire upper digital models. Indirect models digitalised from plaster models were considered as the reference. Two direct digital models were acquired using TRIOS 3 POD intraoral scanners, namely Groups Tr1 and Tr2, wherein intraoral scanning differed in terms of palatal scanning sequences. Based on a modified dental-level superimposition method, 3D measurements of trueness in palate and palatal vault region (PVR) for palatal stable regional superimposition in Groups Tr1 and Tr2, respectively, were performed. Absolute deviations were measured for trueness, while signed deviations were analysed for shape distortion. Colour-coded maps were used for quantitative analysis of deviation distribution pattern. Paired t test was used to analyse differences in palatal trueness between different scanning sequences. One-way repeated-measures analysis of variance and Bonferroni test were used to compare trueness measurements among different superimposition methods. Intraclass correlation coefficient (ICC) was used to verify reproducibility of the proposed method.p = 0.012 < 0.05). Trueness of PVR in Groups Tr1 (127.35 ± 54.11 μm) and Tr2 (118.17 ± 49.52 μm) did not differ significantly (p = 0.149). Moreover, no significant difference was noted in distortion of the palatal region and PVR in Groups Tr1 and Tr2 . A similar pattern of palatal trueness was noted in a majority of participants (22/35). For 3D palatal trueness measurement, there were different applications for different superimposition methods. ICC for the proposed method was > 0.90.Palatal trueness in Group Tr1 (118.59 ± 37.67 μm) was slightly less accurate than that (108.25 ± 33.83 μm) in Group Tr2 .The trial has been registered (registration No:  Dental treatment of any type usually necessitates evaluation of the intraoral situation. With introduction of intraoral scanners in dentistry, direct acquisition of digital impressions is gaining popularity  as it prMost studies on accuracy have focused on dental hard tissues, ranging from single tooth crown to full arches –12, 15. Nevertheless, the soft tissue accuracy of intraoral scanning has not been validated yet owing to scarcity of relevant studies. According to an in vivo study by Gan et al. (2016) , truenesTo our knowledge, to date, none of studies on scanning strategies have focused on palatal soft tissues. Even the User Guide  does not provide any specific description of palatal scanning strategy. Therefore, the effect of scanning sequences on the palatal region should be clarified so that it would be clear to estimate the region displaying a higher deviation in terms of scanning sequences.To date, the two most relevant studies on 3D measurement of accuracy of intraoral scanning in the palatal region have used surface-based registration between intraoral digital models and digitalised plaster models by using a best-fit algorithm , 26. DefAims of this in vivo study were (i) to compare accuracy of 3D measurement of intraoral palatal scans among different superimposition methods; (ii) to investigate the influence on trueness of intraoral palatal scans by using different scanning sequences; and (iii) to assess deviation and its distribution character of trueness in the palatal and PVR region.Thirty-seven students from the School of Stomatology were recruited in this study. Eventually, 35 volunteers successfully finished entire data acquisition. Informed consent was obtained from all participants.Age between 18 and 30 years;Permanent dentition, including premolars symmetrically extracted for past orthodontic treatment with retention stage ended;Good oral hygiene; andGood cooperation to finish all data acquisition.Inclusion criteria were as follows:Undergoing orthodontic treatment or finished orthodontic treatment for no more than 2 years;With more than one-third of tooth defect on a single tooth;With large amounts of metal restorations;With severe crowding or obvious spaces;With palatal defect or lesion;With an abnormally large arch width between bilateral upper first molars; andModerate to severe periodontitis or obvious gingivitis.Exclusion criteria were as follows:Group S: Indirect digital models were utilised as reference. Impressions were recorded using PVS material  by experienced operators in a one-step process, and cast models were fabricated using type IV gypsum . These plaster models were digitalised using a model scanner , the accuracy of which is 20 μm .1occlusal–2palatal–3buccal surfaces in a slow zigzag manner. The upper left second molar was set as the starting point for the initial scan. Whilst scanning palatal soft tissues, scanning was initiated from the palatal side of upper central incisors in a zigzag manner, in accordance with guidelines from a previous study , th, th29], p values < 0.05 were considered statistically significant. Moreover, the intraclass correlation coefficient (ICC) was calculated to verify reproducibility of the superimposition in each region. The reproducibility of 3D measurements in absolute and signed-colour maps was represented by that of Palatal-level superimposition method.One-way repeated-measures ANOVA and Bonferroni post hoc test were used to analyse differences among the four superimposition methods in terms of trueness measurement for the palatal region. On the other hand, paired t test was used to analyse the influence of scanning sequences on palatal trueness and compare the trueness between palatal and dental regions. The study population included 9 men and 26 women, with an age range of 24–27 years. Seventeen participants had undergone orthodontic treatment, of whom, 7 had their premolars extracted. The mean arch width between bilateral upper first molars was 36.68 mm.3D measurements had satisfied reproducibility. ICCs for absolute-deviation and signed-deviation measurements were separately 1.000  and 0.901 .Measured using four methods, trueness of intraoral digital models in Group Tr1 is summarised in Table p < 0.0005), except for comparisons between adjusted dental-level and dental-level methods.For absolute deviations Fig. -a, signip = 0.004 < 0.05).For signed deviations Fig. -b, no siBy using one-way repeated-measures ANOVA, differences in trueness measurement for the palatal region measured using the aforementioned methods were analysed as follows:Furthermore, for 3D measurement of trueness in dentition, all methods except the palatal-level method were analysed using ANOVA:p < 0.0005), except for comparison between adjusted dental-level and upper jaw-level methods.(1) For absolute deviations Fig. -a, signi(2) For signed deviations Fig. -b, signiFor comparison of trueness between palatal region and dentition Table , signifiThe influence of different scanning sequences on palatal trueness was investigated based on the UPRS method. Measurements of palatal trueness in Groups Tr1 and Tr2 are enlisted in Table p = 0.012 < 0.05).On comparing absolute deviations, deviations in Group Tr1 were larger than those in Group Tr2. The difference in mean values was 10.34 μm  and was statistically significant (p = 0.582).On comparing signed deviations, no significant difference was noted between the two groups (p = 0.149). Moreover, compared with palatal trueness, the mean absolute deviation of trueness of PVR was larger without statistical significance. In Group Tr2, the difference in mean values between PVR and palatal trueness was 9.93 μm .On comparing absolute deviations, no significant difference was noted between the two groups (p = 0.615). Moreover, compared with palatal trueness, the mean signed deviation of PVR trueness was smaller without statistical significance. In Group Tr2, the difference in mean values between PVR and palatal trueness was 10.32 μm .On comparing signed deviations, no significant difference was found between the two groups ((i) Middle one-third of the palatal region at the level of second premolars and the distal part on unilateral or bilateral sides Fig. -a①: the (ii) Incisive papilla and the following part at the level between canines and first premolars Fig. -a③: here(iii) Gingival margin: deviations were irregularly distributed.On observing colour-maps, a majority (22/35) of participants from both groups presented a similar pattern of palatal trueness Fig. -a,b. ThrIn addition, directions of larger deviations were almost positive. However, only a few cases (8/22) met all characteristics of the pattern.Moreover, deviation distribution in the rest of the cases (13/35) was irregular and was noted at the level of first and second molars if there were obvious deviations. The deviations were typically ≤500 μm, except for one case in Group Tr1 with negative deviations ranging 485.91–813.95 μm over the left middle one-third of the palatal region at the level of first and second molars.On lateral sides of PVR, it revolves part of middle one-third of the palatal region Fig. -a,c. TheDigital models can be acquired using three methods : directlFor 3D measurement of accuracy, the best method is model superimposition  with comA modified dental-level regional superimposition was proposed in this study. For participants who had undergone orthodontic treatment with premolar extraction, second molars were included in order to increase feature points for regional superimposition because the longer arch length, the larger the deviation of accuracy of dentition , 9. AlthApplications can be analysed using characters of superimposition and the measurements. 1) Both adjusted dental-level and dental-level methods are based on the prerequisite that the morphology of dentition in the intraoral digital impression is accurate  Both adj. When evOf note, when assessing palatal deformation (signed deviations) of intraoral digital impression, standard deviations (SDs) were distinctly higher than means, indicating that local deformation between the palatal region of intraoral digital models and plaster models was relatively unstable and irregular.Because of more characters on posterior teeth and for image stitching based on additional feature points, in Group Tr2, palatal scanning was initiated on the palatal side of posterior teeth. Patterns of deviation distribution in both groups were similar in a majority of participants (22/35). The statistical difference in palatal trueness between Group Tr1 and Group Tr2 was primarily in values of larger deviations. Indeed, the process of image stitching is essential. The impact of scanning sequences on accuracy of dentition can be seen at regions with larger deviations; this results because of error accumulation during the process of image stitching , 13. PalRegarding PVR, the region considered stable for model superimposition in orthodontics, there was no notable impact of different scanning sequences Table . This inCompared with findings from recent studies , 26, theRegarding characteristics of deviation distribution of palatal trueness, findings were similar to that reported by Gan et al. , whereinCompared with palatal trueness, the mean absolute deviation of PVR trueness was slightly higher, and the mean signed deviation of PVR trueness was closer to 0 μm with a larger discrete degree. This indicated that the area proportion of more obvious deformation in PVR was slightly higher than that in the entire palate. Regardless of scanning sequences, PVR trueness of 122.76 ± 48.51 μm was noted . Although a deviation of > 500 μm is considered clinically significant , when asFor 3D PVR superimposition , anterioA major limitation of this study was the influence of flexibility of palatal mucosa on the reference model. To overcome this, selection of the palatal region was accordingly adjusted. However, from the viewpoint of characteristics of deviation distribution, the influence of flexibility during the impression procedure was still unavoidable. Another limitation was sex-imbalance in samples . The area of the palate might be slightly larger in males. To counteract the possible effect of sex-imbalance on transversal and anterio-posterior dimensions of palate, it is better to balance sex distribution in samples. However, the statistical methods applied in this study were about self-control, less impacted by sex distribution. Furthermore, only one type of intraoral scanner was investigated in this study. In future, comparison among different intraoral scanners should be made to explore the divergency in reproducing palatal morphology.When evaluating accuracy of intraoral scanning in the palatal region, the superimposition method should be appropriately adjusted. Palatal trueness is affected by scanning sequences. We recommended that palatal scanning should be initiated at the palatal side of the posterior teeth where the initial scan begins, and the entire palatal scan should be finished along with the arch. Furthermore, when assessing treatment changes by using model superimposition of plaster and intraoral digital models, the average systematic 3D error was 123 μm. For 3D PVR superimposition, we recommend to adjust the distal boundary of the selected region mesially, at the level of the mid-gingival margin of first molars, whilst referring to intraoral digital models.


Human adenoviruses (HAdV) are important pathogens of pediatric respiratory tract infections in Taiwan. There were two major HAdV epidemics in southern Taiwan in 2011 and 2014, respectively.The demographic, clinical characteristics, and risk factors for hospitalization of pediatric patients with HAdV infection in the two outbreaks were retrospectively compared. The epidemic was defined as > 7% HAdV detection rate for six consecutive weeks. HAdV infection was defined as positive HAdV isolates from respiratory tract specimens. HAdV genotype was determined by PCR-based hexon gene sequencing.p < 0.001) and was replaced by other genotypes  in the 2014 epidemic. Among the hospitalized patients, there were more patients hospitalized with bronchopneumonia/or pneumonia in the 2011 epidemic , while more patients hospitalized with acute pharyngitis/pharyngoconjunctival fever  in the 2014 epidemic. In both epidemics, hospitalized patients had higher WBC and C-reactive protein (CRP) levels than non-hospitalized patients. Using multivariate regression analysis, underlying disease and elevated CRP levels were independent risk factors for hospitalization in both epidemics.A total of 1145 pediatric patients were identified . HAdV genotype 3 and 7 contributed to both epidemics, although the proportion of HAdV3 decreased significantly (64.7% in 2011 to 25.5% in 2014, There were significant differences in clinical, viral characteristics and risk factors of hospitalization between the 2011 and 2014 epidemics. Understanding changes in the epidemiological and clinical characteristics of HAdV epidemics is important from a public health perspective. The 2011 and 2014 HAdV epidemics in Taiwan were caused by different HAdV genotypes.Hospitalized patients had higher WBC and CRP levels than non-hospitalized patients.Underlying disease and elevated CRP were independent risk factors of hospitalization.Human adenoviruses (HAdVs) are double stranded non-enveloped DNA viruses which cause a wide range of illnesses including acute respiratory infections (ARIs), gastroenteritis, conjunctivitis, cystitis, and meningoencephalitis. HAdV infection accounts for 5–7% of respiratory illnesses in children and infants , 2. HAdVThere was a significant increase in the incidence of HAdV infection in southern Taiwan between 1999 and 2002, with three outbreaks of adenovirus respiratory infection between November 1999 and December 2001. HAdV3 and HAdV7 were the major serotypes in the first outbreak, while HAdV4 was the major serotype in the second and third outbreak , 13. SpeThe most recent HAdV outbreak in Taiwan was in 2014. However, currently available molecular epidemiology data from this outbreak have not been completely analyzed. In this study, we conducted a molecular characterization of HAdV from the 2014 epidemic, and compared the demographics, clinical characteristics, and risk factors of hospitalization and pneumonia in patients between the 2011 and 2014 epidemics.This study retrospectively enrolled pediatric patients with virologically-confirmed HAdV infection who presented at the National Cheng Kung University Hospital (NCKUH), a national university-affiliated, 1200 bed teaching hospital, which is also the major tertiary referral center in southern Taiwan. This study enrolled patients (< 18 years old) who were diagnosed with HAdV between Nov. 2010 to Dec. 2015. HAdV infection is defined based on the presence of HAdV isolated from clinical specimens, including nasopharyngeal aspirates, throat or nasal swabs. The patient list of HAdV infections was abstracted from the hospital-based administrative electronic data. Patients without complete clinical information available for analysis and adult patients were excluded. The NCKUH virology laboratory is one of the contracted laboratories of the nationwide viral surveillance system of the Center for Disease Control (CDC), Taiwan. HAdV epidemics are defined as HAdV-positive rate above 7.0% for six consecutive weeks according to baseline epidemiological surveys  . The ch3 Ultra DFA (direct fluorescent antibody) respiratory virus screening and identification kit . After immunofluorescent confirmation of HAdV infection, the cell culture lysate were stored at − 70 °C for further genotype determination. Viral DNA was extracted from 200 μL of the original adenovirus-positive specimen using the QIAamp DNA Blood Mini Kit (Qiagen) according to the manufacturer’s instructions. A 1004 bp fragment of the hexon gene was PCR-amplified from 5 μL of eluted samples using primers AdTU7 (5′-GCCACCTTCTTCCCCATGGC-3′) and AdTU4′ (5′-GTAGCGTTGCCGGCCGAGAA-3′). These amplicons were then sequenced on a 3730 xl DNA Analyzer (Applied BioSystems). The forward and reverse sequences were combined using BioEdit (Ibis Therapeutics) and sequence alignment was performed with 51 previously characterized prototype viruses, as well as other characterized genotypes from GenBank and our internal sequence collection. A good genotype matche was defined as specimens which resulted in > 90% alignment identify score.Throat swabs, nasopharyngeal swabs or aspirates were collected in viral transport medium, and inoculated into tubes containing Madin-Darby canine kidney cells, Vero cells, A549 cells or rhabdomyosarcoma cells within 24 h of collection. Cells were incubated at 37 °C and viral cytopathic effect was evaluated daily for a minimum of 14 days. HAdV infection was confirmed with immunofluorescent assays using Dp < 0.05 through univariate logistic regression analysis were selected into the multivariate logistic regression model. Multivariate logistic regression analysis was performed to investigate the risk factors associated with hospitalization and pneumonia. All statistical analyses were performed using the IBM SPSS statistical software version 22 for Windows . Two-tailed P values < 0.05 were considered statistically significant.Categorical variables were presented as counts and percentages and tested by Chi-square test or Fisher’s exact test. Continuous variables were presented as mean and standard deviation and tested by independent sample t-test. Variables with P < 0.001) ; cases with prolonged fever or severe enough to visit ER, or warranting hospitalization received further investigation, including urine analysis, blood culture, or bacterial culture from sterile or non-sterile sites. Blood culture results were evaluated for all febrile hospitalized children in order to exclude occult bacteremia. Isolation of other respiratory pathogens including bacteria, or viruses other than HAdV was defined as co-infection. However, patients with severe definite bacterial infection, including bacteremia and urinary tract infection were excluded from this cohort. Fifty-three adult patients were also excluded. Analysis of the monthly distribution of HAdV infection showed that HAdV circulated year-round, but there were two major HAdV outbreaks during the study period , while a significantly higher proportion of patients had acute gastroenterocolitis-related symptoms (diarrhea and vomiting) in the 2011 epidemic . The 2011 epidemic had a significantly higher percentage of genotype 2 and genotype 3 infections compared to the 2014 epidemic (both p < 0.001), while the 2014 epidemic had a significantly higher percentage of genotype 1, genotype 4 and genotype 6 infections .We compared the demographics and clinical characteristics of patients between the 2011 and 2014 HAdV epidemics (Table p = 0.045). There was a significantly higher percentage of non-hospitalized patients with acute pharyngitis/PCF (p < 0.001), while there was a significantly higher percentage of bronchiolitis/bronchopneumonia (p < 0.001), pneumonia (p < 0.001) and acute gastroenterocolitis (p = 0.016) among hospitalized patients. A significantly higher percentage of hospitalized patients had underlying disease compared to non-hospitalized patients (p = 0.001). Clinical manifestations showed that a significantly higher percentage of non-hospitalized patients had injected throat (p = 0.004) compared with hospitalized patients, while a significantly higher percentage of hospitalized patients had cough and diarrhea compared with non-hospitalized patients (both p < 0.05). Laboratory values showed that hospitalized patients had significantly higher mean WBC , absolute lymphocyte count (ALC) counts , and mean CRP values  compared to non-hospitalized patients.Differences in demographics and clinical characteristics of hospitalized and non-hospitalized patients were compared between the 2011 and 2014 epidemic (Table p < 0.001). There was a significantly higher percentage of non-hospitalized patients with acute pharyngitis/PCF compared to hospitalized patients (p < 0.001), while a significantly high percentage of hospitalized patients had bronchiolitis/bronchopneumonia and pneumonia (both p < 0.001). A higher percentage of hospitalized patients had underlying disease (p < 0.001). There was a significantly higher percentage of non-hospitalized patients with cough and vomiting compared to hospitalized patients (both p < 0.05). Laboratory values showed that hospitalized patients had significantly higher mean WBC counts , and CRP values  compared to non-hospitalized patients.During the 2014 epidemic, a higher percentage of hospitalized patients had co-infections compared to non-hospitalized patients (p = 0.031), with diagnosis of acute pharyngitis/PCF , and presented the symptoms of fever (100.0% vs. 88.9%), injected throat (96.2% vs. 83.1%), cough (88.6% vs. 79.9%) and rhinorrhea  during the epidemic 2014. However, higher proportion of patients were hospitalized with the diagnosis of pneumonia in the 2011 epidemic than in the 2014 epidemic (10.6% vs. 5.1% p = 0.006).Comparison of hospitalized patients during the 2011 and 2014 epidemics showed higher percentage of patients had co-infection , cough , and increased CRP values . In the 2014 epidemic, the risk of hospitalization was significantly increased in patients with co-infections , bronchiolitis/ bronchopneumonia , underlying disease , diarrhea , vomiting , increased WBC counts  and increased CRP values . Using a cutoff value of CRP = 60 in univariate logistic regression analysis, in the 2011 and 2014 epidemics, the risk of hospitalization was significantly increased in patients with CRP values > 60 . Underlying disease and elevated CRP level were independent risk factors for hospitalization in both epidemics.Multivariate logistic regression analysis to identify the risk factors associated with each epidemic was listed in Table Diagnosis of radiologically-conformed alveolar pneumonia was according to World Health Organization (WHO) criteria . Presencp = 0.012). Among the co-infections, viral infection (75%) was more predominant than bacterial infection in the pneumonia group. Pneumonia patients had significantly higher mean WBC counts , and CRP levels , but lower mean ALC  compared to non-pneumonia patients. There was no significant difference in genotype distribution between pneumonia patients and non-pneumonia patients.There were 29 patients diagnosed with HAdV pneumonia in the two epidemics. We compared the demographics and clinical characteristics of these 29 patients with non-pneumonia patients Table . There wIn this study, we compared the demographics, clinical characteristics, and risk factors of hospitalization and pneumonia in patients from the 2011 and 2014 adenovirus epidemics in southern Taiwan. Genotype 2, 3 and 7 accounted for the majority of infections in the 2011 epidemic. Although genotype 3 and 7 sustained to contribute to the 2014 epidemic, these genotypes comprised < 50% of cases in the 2014 epidemic. The surge of other genotypes, including 1, 4 and 6 constituted the other half of genotypes found in the 2014 epidemic. In addition to genotype, there were also differences in the clinical characteristics, laboratory values, and hospitalization between the two epidemics. Our analysis showed that the 2011 epidemic was mainly caused by HAdV3 and HAdV7, with a higher prevalence of HAdV3 compared to HAdV7 (64.7% vs. 16.7%). This finding was consistent with other epidemiological reports, showing co-circulation of HAdV3 and HAdV7 in the 2011 epidemic –19, 21. The clinical presentations varied among different HAdV serotypes. Lin et al. reported that HAdV3 more likely to cause upper respiratory tract infections, while HAdV7 tends to cause lower respiratory tract infections and a more severe clinical course, including longer duration of fever and hospital stay, and need for intensive care . Many otAs well as viral genomic characteristics, host susceptibility is a major risk factor for severe HAdV infection. The neurological disease, chronic lung disease, and airway anomalies were reported to be related to HAdV pneumonia , 21. NeuOur data showed that in both epidemics, hospitalized patients had higher WBC counts and CRP levels compared with non-hospitalized patients. Leukocytosis and elevated CRP levels are common in HAdV infection, even without superimposed bacterial infection . HoweverHAdV pneumonia is the most common manifestation of severe HAdV infection in immunocompetent patients, but accounts for less 5% of all HAdV infection . In our As discussed by Chen et al. study , seven sThere are some limitations in this study. First, molecular typing was done in only 24 and 30% of all HAdV isolates, in 2011 and 2014 respectively through random sampling. But, the number of viral isolates chosen for further genotype in each epidemic is relative large compared with all other studies conducted in Taiwan during the same period of time. Also, our genotype distribution result is compatible with other epidemiological studies in Taiwan in 2011 . Second,We found co-circulation and emergence of different HAdV genotypes in the 2011 and 2014 epidemics. The 2011 epidemic was mainly caused by HAdV genotype 3 and 7 and had more gastrointestinal symptoms, while the 2014 epidemic was caused by genotype 1, 2, 3, and 7 and had more upper respiratory tract infections. Underlying disease and high CRP levels were independent risk factors of hospitalization in both epidemics. Understanding the changes in epidemiological and clinical characteristics of HAdV epidemics is important from a public health perspective.


Head trauma is common in the emergency department. Identifying the few patients with serious injuries is time consuming and leads to many computerized tomographies (CTs). Reducing the number of CTs would reduce cost and radiation. The aim of this study was to evaluate the characteristics of adults with head trauma over a 1-year period to identify clinical features predicting intracranial hemorrhage.Medical record data have been collected retrospectively in adult patients with traumatic brain injury. A total of 1638 patients over a period of 384 days were reviewed, and 33 parameters were extracted. Patients with high-energy multitrauma managed with ATLS™ were excluded. The analysis was done with emphasis on patient history, clinical findings, and epidemiological traits. Logistic regression and descriptive statistics were applied.Median age was 58 years . High age, minor head injury, new neurological deficits, and low trauma energy level correlated with intracranial hemorrhage. Patients younger than 59 years, without anticoagulation or antiplatelet therapy who suffered low-energy trauma, had no intracranial hemorrhages. The hemorrhage frequency in the entire cohort was 4.3% (70/1638). In subgroup taking anticoagulants, the frequency of intracranial hemorrhage was 8.6% (10/116), and in the platelet-inhibitor subgroup, it was 11.8% (20/169).This study demonstrates that patients younger than 59 years with low-energy head trauma, who were not on anticoagulants or platelet inhibitors could possibly be discharged based on patient history. Maybe, there is no need for as extensive medical examination as currently recommended. These findings merit further studies. During the twentieth century, patients with traumatic brain injury and loss of consciousness presenting in the emergency department were admitted for further observation. If they deteriorated during observation, computerized tomography (CT) was performed. Modern guidelines for managing traumatic brain injury in the emergency room have been utilized now for well over a decade and has alleviated clinical practice. When these guidelines are applied correctly, approximately 50% of the patients undergo head CTs .Repetitive CT of the head may be related to adverse effects later in life. Even though modern CT machines are using less and less radiation, X-ray-induced cancer is something the clinician must take into account –5.Modern guidelines are based on the previous epidemiological studies, which have shown a bimodal distribution of age, with the lowest incidence around 55 years of age. The highest incidence in the adult population is seen among young adults  and the elderly –12.A randomized, controlled study from the same era showed that upfront CT when presenting in the emergency department was sufficient to rule out intracranial hemorrhage in most patients. They could be safely discharged . North AThe common denominator for all degrees of traumatic brain injury is that the patient has sustained mechanical energy to the head from external physical force. However, trauma energy level varies. Both academic definitions and clinical guidelines are based primarily on level of consciousness, degree of head injury, and the temporal progression of level of consciousness. Neither the Canadian CT Head Rule, the New Orleans Criteria, nor the Scandinavian Neurotrauma Committee guidelines base decisions to dismiss patients on patient-stated trauma energy alone, suggesting that clinical status is the most important factor . These gIf patient history alone could be used as a “rule-out criterion” for intracranial hemorrhage, emergency department workloads and radiation levels could be reduced, resulting in both economic and public health benefits.The aim of this study was to evaluate the characteristics of adults presenting with the chief complaint of head trauma over a 1-year period to identify clinical features predicting intracranial hemorrhage. The analysis was done with particular emphasis on patient history, clinical findings, and epidemiological traits.The study was conducted as a retrospective analysis of medical records of patients presenting with head trauma at the emergency department of Helsingborg General Hospital. This hospital serves a geographic area of 350,000 people. The emergency department has approximately 72,000 visits annually. It has trauma surgeons, general surgeons, orthopedic surgeons, emergency medicine doctors, anesthesiologists, and otorhinolaryngologists. The nearest neurosurgical clinic is 40 km away. Multitrauma patients are managed according to ATLS™.n = 647) were excluded to make the patient cohort more representative of the majority of emergency-room patients with head injury. Furthermore, the hospital manages multitrauma patients with a different algorithm, which we did not seek to evaluate. The review was performed on patients registered between November 11, 2013, and November 30, 2014, a total of 384 days.When presenting to the emergency department, patients were registered in an electronic patient registry. Its purpose was to keep track of room location and chief complaint. After extracting a list of all patients 18 years or older who registered with the chief complaint “head injury,” we reviewed the medical records. Patients may have had other minor injuries as well, but were not initially classified as multitrauma. High-energy multitrauma patients .Gender (m/f).Head CT performed (yes/no).Head CT outcome (hemorrhage/no hemorrhage).Admission to general hospital ward (yes/no).Admission to intensive care unit (ICU) (yes/no).Admission to neuro intensive care unit (neuro ICU) (yes/no).Neurosurgical intervention (yes/no).Degree of head injury .Level of consciousness using Reaction Level Scale 85 (RLS85) (1–8).Level of consciousness using Glasgow Coma Scale (GCS) (15–3).Blood pressure (systolic mm Hg/diastolic mm Hg).Pulse rate (beats/minute).Size of pupils (mm).Body weight (kilograms).Height (meters).Past medical history (yes/no).Anticoagulant treatment (no/warfarin/noac/injection).Platelet inhibitor treatment (no/aspirin/clopidogrel/ticagrelor/other).Other medication (yes/no).Preexisting/new focal neurological deficits (yes/no).Deterioration of neurological status during observation (yes/no).S100B level (µg/L).Nausea (yes/no).Vomiting (yes/no).Number of vomits (n).Amnesia, type and duration .Loss of consciousness (yes/no).Peritraumatic seizure (yes/no).Posttraumatic headache (yes/no).Increasing intensity of headache (yes/no).Trauma energy levels .Clinical signs of basal skull fracture (yes/no).Orthostatic hypotension (yes/no).Cardiac dysrhythmia (yes/no).Time from injury to medical examination at the emergency department (hh:mm).Influence of any or multiple drugs/alcohol (yes/no).Level of trauma energy (see #32 above) was interpreted on the basis of trauma mechanism, as follows:Low : fall frMedium : fall fr™): fall from 3 m or more, motor vehicle accident at 70 km/h or more with seatbelt, motor vehicle accident at 30 km/h or more without seatbelt, any motorcycle accident, pedestrian hit by motor vehicle.High  in a multivariate logistic regression model. Another multivariate logistic regression was performed on the significant parameters (p < 0.05) of the first multivariate regression. Missing data were replaced by series median. Post hoc subgroup analysis with descriptive statistics was performed to ascertain the effect of different parameters on intracranial hemorrhage to determine the clinically significant age cutoff.Data were analyzed using SPSS version 21 for Mac. Q–Q plots and the Shapiro–Wilk formula were used to test for normal distribution. Central tendencies are presented as medians when skewed. Post hoc multivariate analysis was performed on all relevant and applicable parameters; this analysis was performed via univariate binomial logistic regression and the insertion of significant parameters  had minimal head injury, 922 (56.3%) had mild head injury, 18 (1.1%) had moderate head injury, 4 (0.2%) had severe head injury, and 238 (14.5%) were not assessable. Twelve patients were admitted to intensive care unit and 5 of these had neurosurgical intervention. Level of consciousness was classified according to the Scandinavian reaction level scale (RLS-85) in 1608 (98.2%) cases. Only 47 cases (2.7%) were classified according to GCS.During the study period, 842 CTs were performed, representing 51.4% of the patients. Of these, 588 (69.8%) were performed on patients with low-energy trauma. The median age of patients who did not undergo CT was 48 years  and that of patients who underwent CT was 67 years . See Fig. In multivariate logistic regression of 12 applicable predictor variables, only 4 were statistically significant: high age, minor head injury, new neurological deficits, and low trauma energy level . Some parameters were excluded due to > 30% missing values .n = 826/1638 [50.4%]), no intracranial hemorrhage was found in patients with low-energy trauma. When not stratifying this age cohort according to intracranial hemorrhage, patients with all degrees of head injury were found. No patients in this subgroup had anticoagulants or platelet inhibitors. Of the patients with intracranial hemorrhage, two were missing the trauma-energy parameter  were admitted to the surgical ward due to head trauma. Seven (0.4%) patients were cared for at the ICU and five (0.3%) patients underwent neurosurgical intervention and received care at the neuro ICU. 70/1638 (4.3%) patients had intracranial hemorrhage. Of the patients undergoing CT scan, 8.3% had intracranial hemorrhage. 76% of patients sustained low-energy force. 6% sustained medium energy trauma, 1.5% sustained high-energy trauma, and in 17.5% of cases, it was not assessable.The distribution of intracranial hemorrhage was 45/70 64.3%) in males and 25/70 (35.7%) in females  had no thrombocyte aggregation inhibitor, and 169 (11.3%) had some sort of thrombocyte aggregation inhibitor, where 75 mg ASA accounted for most cases (148/1638). The other 21 patients had treatment with Clopidrogrel 75 mg, Ticagrelor, or a combination of these.Moreover, 1,505 (91.9%) had no anticoagulation, 119 (7.3%) had warfarin, and 18 (1.1%) had oral anticoagulants or injections of low-molecular-weight heparin with varying dosage.Of the patients, 23.3% were intoxicated with alcohol, and 25% in total were intoxicated with some kind of drug or a combination of drugs.Moreover, 92% were assessed using the Reaction Level Scale 1 (RLS1) on their arrival to the emergency department. Of these, 28% had deteriorating mental status  during their emergency-department stay. Observed deterioration of mental status was not associated with higher frequency of intracranial hemorrhage.Patients without anticoagulants and platelet inhibitors who suffered head trauma had a 3% (40/1351) incidence of intracranial hemorrhage. The hemorrhage frequency in the entire population was 4.3% (70/1638). Among patients on anticoagulants, the frequency of intracranial hemorrhage was 8.6% (10/116), and it was 11.8% (20/169) among those on platelet inhibitors (Table S100b was measured in 198/1638 cases. Sensitivity was 87.5%, specificity was 46.0%, the negative predictive value was 0.989, and the positive predictive value was 0.064 (Table This study showed that high age, male gender, low trauma energy, low degree of head injury, and new neurological deficits were correlated with intracranial hemorrhage. These correlations are in accordance with the previous studies and do not reveal any new clinically significant information , 14. To Because of the results of the logistic regression analysis, subgroup analysis was performed. This yielded the large group of patients 58 years or younger who did not have any intracranial hemorrhage when trauma energy was low and who did not take anticoagulation and/or antiplatelet therapy. However, because of unreliable patient history with regard to trauma energy in two of the cases, hemorrhages were found also in this age cohort. The in-depth analysis of these two cases revealed that trauma energy level could not be determined.The validity of this subgroup finding is debatable because of missing data, but it certainly merits further prospective studies. A retrospective analysis of this kind has two main issues of bias to take into account. First, the data are entered into medical records by different physicians who all make individual and slightly different assessments. Second, the medical record data were interpreted by another person and converted to categorical data. We tried to reduce this bias using a rigorous set of rules for how data should be categorized during data collection. We are currently planning a study to evaluate the validity of the present findings, where data will be prospectively recorded and categorized upon collection to minimize bias.In the Canadian CT Head Rule, medium trauma energy is used as a “rule-in criterion” for head CT, regardless of clinical presentation. However, low trauma energy is not used as a “rule-out criterion.” In the case of low trauma energy, signs and symptoms guide the decision of whether to use CT . In the The present study indicates the possibility of ruling out intracranial hemorrhage in some patients based on patient history alone, regardless of clinical status.The epidemiological analysis shows slightly higher average age compared to the previous studies However, this trend was demonstrated by Roozenbeek et al. in a large meta-analysis . This inThe present study indicates a higher frequency of intracranial hemorrhage in patients with antiplatelet medication than in patients with anticoagulants. These results are in accordance with the previous studies by Nishijima et al. . Both ouThe study design, a retrospective review of medical records, has certain limitations. Therefore, one has to be careful not to jump to conclusions based on its results. However, if these findings are reproducible in a prospective study, almost half of the adult patients with traumatic head injury may be safely discharged by the triage nurse based on patient history alone. This would eliminate further medical examination and irradiation and warrants further evaluation in a prospective study, where patient history and trauma energy play a central role in management.This retrospective study demonstrates that patients younger than 59 years, with low-energy head trauma who were not on anticoagulants or platelet inhibitors could have been discharged after complete patient history and may not have needed as extensive medical attention as currently recommended and here given. These findings merit further studies.