Although several studies have investigated the effects of diabetes on hearing loss, the relationship between these two conditions remains unclear. Some studies have suggested that diabetes may cause sensorineural hearing loss, whereas others have failed to find an association. The biggest challenge in investigating the association between diabetes and hearing loss is the presence of confounding variables and the complexity of the auditory system. Our study investigated the association between diabetes and sensorineural hearing loss. We evaluated the influence of time from diabetes diagnosis on this association after controlling for age, gender, and hypertension diagnosis and excluding those subjects with exposure to noise.This cross-sectional study evaluated 901 adult and elderly Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) participants from São Paulo, Brazil who underwent audiometry testing as part of ELSA-Brasil’s baseline assessment.Hearing thresholds and speech test results were significantly worse in the group with diabetes than in the group without diabetes. However, no significant differences were found between participants with and without diabetes after adjusting for age, gender, and the presence of hypertension. Hearing thresholds were not affected by occupational noise exposure in the groups with and without diabetes. In addition, no association between the duration of diabetes and hearing thresholds was observed after adjusting for age, gender, and hypertension.We found no association between the duration of diabetes and worse hearing thresholds after models were adjusted for age, gender, and the presence of hypertension. The burden of diabetes is increasing worldwide In addition to the cardiovascular outcomes and the long-term damage to the kidneys, eyes, and nervous system caused by diabetes The pathological support to this association may be related to an increase in capillary lesions in the cochlea, more specifically in the stria vascularis and basilar membrane. Other studies have also reported a reduction in the number of spiral ganglion neurons. These differences could be related to the duration of diabetes and to comorbidities that could affect the inner ear Although several studies have investigated the effects of diabetes on hearing loss (HL), the relationship between these two conditions remains unclear. Some studies have suggested that diabetes may cause sensorineural hearing loss (SNHL) In this study, we investigated the association between diabetes and SNHL. We evaluated the influence of other factors such as age, gender, exposure to noise, hypertension diagnosis, and duration of diabetes on this association.This study was approved by the Ethics Committee of the University Hospital at University of São Paulo (n 883/09).In this ancillary cross-sectional study, we evaluated 901 ELSA-Brasil participants from São Paulo  who were invited to participate in the study and agreed to undergo audiometry testing as part of ELSA-Brasil’s baseline assessment. Informed consent was given by all participants. The study was approved by the Ethics Committee of the University Hospital at University of São Paulo (n 883/09).The design, objectives, and cohort profile of ELSA-Brasil have been published in detail elsewhere After otological inspection, an audiological assessment was conducted. Screening acoustic immittance measurements (Madsen Otoflex 100) were performed to exclude middle ear disorders.Pure-tone audiometry was performed using air conduction at octave frequencies from 250-8,000 Hz and bone conduction at 500-4,000 Hz.Speech tests included the Speech Reception Threshold (SRT) and the Speech Discrimination Score (SDS). The SRT assesses people’s ability to hear and understand standardized three-syllable words (threshold in decibel hearing level (dBHL)), and the SDS evaluates people’s ability to hear and understand standardized one-syllable words (percentage of words correctly identified).All tests were performed using a Madsen Itera II audiometer in a sound-proof room.Socio-demographic characteristics and medical and occupational histories were obtained. Diabetes was defined as follows: medical history of diabetes; reported use of medications to treat diabetes; fasting serum glucose ≥7 mmol/l; glycated hemoglobin (HbA1c) level ≥48 mmol/mol; or 2-h oral glucose tolerance test with 75 g of glucose ≥11.1 mmol/l. Hypertension was defined as follows: reported use of medications to treat hypertension; systolic blood pressure ≥140 mmHg; or diastolic blood pressure ≥90 mmHg. Dyslipidemia was defined as follows: reported use of lipid-lowering treatment or low-density lipoprotein (LDL) cholesterol level ≥3.36 mmol/l.Audiometric and speech test variables were compared between left and right ears in each group (D: group with diabetes and ND: group without diabetes). No significant differences were found between the left and right ears, they were grouped. Then, we calculated the mean values (both ears together) for the following measures: each audiometric frequency (threshold by frequency); low- to middle-range frequencies ; high-range frequencies ; SRT and SDS. For each audiometric frequency mean, a value >25 dBHL was considered HL Continuous variables were expressed as means ± SD, and categorical variables were expressed as proportions. The chi-square and Kruskal-Wallis tests and one-way analysis of variance (ANOVA) were used whenever applicable. We constructed linear regression models using the hearing threshold values, SRT, and SDS for each frequency as dependent variables to evaluate their association with diabetes. The following models were constructed: We constructed similar models including only individuals with diabetes (N=191) to determine if the time from diabetes diagnosis was associated with HL. In this analysis, we set cutoff times at 1, 5, 7, and 9 years from diagnosis. We also performed a sensitivity analysis excluding individuals with a history of noise exposure. All analyses were performed using R software v.3.1.2. The significance level was set at 0.05.Of the 901 participants, 191 (21.2%) had diabetes. Among those with diabetes, HbA1c levels were available for 190 participants (99.5%), and adequate glycemic control (<53 mmol/mol) was found in 149 (78.4%) participants. We also analyzed the audiometric measurements using linear models. p-values 0.627; 0.489; 0.785; 0.611; 0.477; 0.914; 0.207; 0.277; 0.172; and 0.478, respectively). Similarly, no significant differences in hearing thresholds or speech tests were found between the D and ND groups at 1, 5, or 7 years from diagnosis after adjusting for age, gender, and presence of hypertension.We also performed a subgroup analysis of participants with diabetes to evaluate the association between hearing loss and time from diabetes diagnosis. Among the 191 participants, 3 (1.6%) could not precisely time their diabetes diagnosis and were excluded from these analyses. Among the remaining 188 individuals, 98 (52.1%) did not report themselves as diabetic and were diagnosed based on the results of the ELSA-Brasil laboratory baseline assessment. Therefore, these subjects were considered as having a time from diabetes diagnosis of zero. Participants in the D group were grouped according to the time from diagnosis (<9 years or ≥9 years). Although the mean hearing threshold for most frequencies and the SRT were lower in participants diagnosed ≥9 years than in those diagnosed <9 years, no significant differences were found after adjusting for age, gender, and the presence of hypertension  and 260 participants in the ND group (36.6%) with a history of noise exposure. In both groups, the mean hearing thresholds were not significantly different after these participants were removed from the analysis. The We investigated the association between diabetes and SNHL in ELSA-Brasil participants from the São Paulo investigation center. In crude models, we found significant differences between the D and ND groups in most variables evaluated, including demographic characteristics (age and gender), fasting blood collection and blood pressure variables. Participants in the D group were older, and there were also more men and more hypertensive participants in the D than ND group.Although the LDL and total cholesterol levels were higher in the D group, no significant differences were found between groups. Conversely, triglyceride levels were significantly higher in D than in ND participants. Similar findings were reported by Kakarlapudi et al. In the crude model, pure-tone audiometry thresholds and speech test results were significantly worse in the D group than the ND group . These fAnalysis of the crude model  supportsA meta-analysis by Horikawa et al. A meta-analysis by Akinpelu et al. Uchida et al. Thus, we attempted to control for these possible confounding factors in our study and determine whether the differences observed in the initial analyses  at ELSA-Brasil baseline. Thus, we assume that these participants did not have advanced microangiopathy, and their cochlear tissues were not directly affected by diabetes due to good control of the condition. This hypothesis could explain the lack of difference in hearing thresholds between the D and ND groups after adjusting for age, gender, and hypertension.The adequate glycemic control in our study population may be related to the nature of ELSA-Brasil, as cohort volunteers are potentially more health-conscious than the general population. Thus, this fact should be considered when comparing our results to those from other cross-sectional analyses.This study found no association between diabetes and worse hearing thresholds after adjusting for age, gender, and presence of hypertension. It should be noted that the diagnosis of diabetes was based on objective measures, and we also included confounding variables such as age, gender, presence of hypertension, noise exposure, and duration of diabetes, which have not been examined simultaneously in all studies on the effect of diabetes on SNHL. However, the mean age of participants and the duration of diabetes were relatively low in our study population, and glycemic control was adequate, which may have affected our findings.Hearing thresholds and speech test results were significantly worse in D than in ND participants. However, after adjusting for age, gender, and the presence of hypertension, no significant differences were found between the groups. In addition, hearing thresholds were not affected by noise exposure in D or ND participants. Together, these findings revealed no association between the duration of diabetes and worse hearing thresholds after adjusting for age, gender, and hypertension.Samelli AG conceived and designed the study, was responsible for acquisition, analysis and interpretation of data, drafted and critically revised the manuscript for important intellectual content and approved the manuscript final version to be published. Santos IS participated in the analysis and interpretation of data, critically revised the manuscript for important intellectual content and approved the manuscript final version to be published. Moreira RR, Rabelo CM and Rolim LP participated in the acquisition of data, critically revised the manuscript for important intellectual content and approved the manuscript final version to be published. Bensenõr IJ revised the article critically for important intellectual content and approved the final version of the manuscript to be published. Lotufo PA critically revised the manuscript for important intellectual content and approved the final version of the manuscript to be published.


The burden of metabolic risk factors for cardiovascular disease (CVD), such as type 2 diabetes, elevated cholesterol and hypertension, is unequally distributed across ethnic groups. Recent findings suggest an association of infectious burden (IB) and metabolic risk factors, but data from ethnic groups are scarce. Therefore, we investigated ethnic differences in IB and its association with metabolic risk factors.Helicobacter pylori. Associations between IB categories 4–6 (high), 3 (intermediate) and 0–2 (low) infections and metabolic risk factors were assessed by logistic regression. Finally, we determined the contribution of IB to the association between ethnicity and the metabolic risk factors by comparing adjusted logistic regression models with and without IB categories.We included 440 Dutch, 320 Turkish and 272 Moroccan participants, 18–70 years, of the 2004 general health survey in Amsterdam, the Netherlands. IB was defined by seropositivity to the sum of 6 infections: Herpes Simplex Virus 1 and 2; Hepatitis A, B and C; and A high IB was more frequently observed among the Turkish and Moroccans than among the Dutch. After adjustment for age, sex, ethnicity, educational level, physical activity and body mass index, high IB was associated with type 2 diabetes (odds ratio high vs low IB (OR) =2.14, 95%-confidence interval (CI) 1.05–4.36). The association was weaker and not statistically significant, for elevated cholesterol  and hypertension . IB attenuated ethnic differences particularly for type 2 diabetes.Our study showed that Turkish and Moroccan adults in Amsterdam have a higher IB than Dutch adults, which was associated with the differences in type 2 diabetes. Due to the cross-sectional nature of the study, we cannot draw a conclusions with regards to the time-sequence of cause and effect. Nevertheless, the findings ask for further research into the nature of association of IB with metabolic risk factors in a longitudinal setting. Cardiovascular disease (CVD) is the leading cause of death worldwide  and mortNumerous studies have shown the importance of infections by single infectious agents in the development of CVD –13. HoweHelicobacter pylori (H.pylori) compared to non-Hispanic whites . ResultH.pylori was tested by means of H.pylori serology for the strains 26,695 and G27, specifically for antibodies against proteins: HP0073, HP0243, HP0010, HP1564, HP0547/1, HP0547/2, HP0887/1, HP0887/2, HP1098 and HP0659/1. Values above and including 200 MFI were defined as seropositive. This threshold was based on percentile distribution plots, since there was no external reference panel available. Seropositivity to at least 4 proteins was considered as H.pylori –positive, since this has shown good agreement (κ = 0.70) with serologic assay classification [fication .Ethnicity was defined according to the definition of the Dutch Ministry of Internal Affairs by the self-reported country of birth of the participant or the participant’s father or mother , 32.Highest level of education attained was used as a proxy for socio-economic position . Low wasCurrent cigarette smoking was defined according to self-reported smoking at time of the interview. Being physically active was defined according to the Dutch norm for healthy physical activity, as at least half an hour of moderate activity on at least 5 days a week . Body maDiabetes was defined by self-reported diabetes and/or by the use of anti-diabetic medication  and/or by a measured non-fasting glucose level of > 11.0 mmol/L and/or a measured HbA1c level of > 48 mmol/mol . ElevateWe defined IB as the total number of infections. With the term infection we here refer to antibody seropositivity, a measure reflecting current or past infection. For analysis, IB was divided into categories based on the distribution in the population .We used means (standard errors (SE)), medians (IQR), or n (percentages) to describe the baseline characteristics of participants in the three ethnic groups. Differences between the ethnic groups were calculated by chi square tests or Kruskal Wallis tests. We then described the IB and infection prevalence, and determined the age and sex-adjusted differences in high IB (versus the combined intermediate and low IB categories as a reference) and in individual infections with logistic regression.p > 0.05 for the likelihood ratio test). We repeated these analyses for the individual infections.Subsequently, we analyzed the association of IB categories with diabetes, elevated cholesterol and hypertension by means of logistic regression analysis. We adjusted for age, sex and ethnicity. In an additional analysis, we also adjusted for education level, physical activity and BMI. Moreover, we repeated the analysis after exclusion of people with a self-reported diagnosis. We reported all associations for the total population, as analysis of effect modification did not show evidence of a difference in association by ethnicity .All statistical tests were two-tailed and Between 41% (Dutch) and 58% (Moroccan) of participants were men  that have been associated with metabolic risk, and included by others in their definition of IB. On the other hand, we included data on HAV, HBV and HCV, which some but not all of these other studies included. The inconsistency across studies may also reflect the lack of insight into the exact mechanisms of risk and indicates the importance of further work to determine which infections or combinations of infections associate most strongly with metabolic risk.The consistently positive association of IB with prevalent diabetes and the non-significantly positive associations with elevated cholesterol and hypertension in our population support a possible association between IB and these metabolic risk factors. Previous studies have been inconsistent. For example, several studies reported positive associations with diabetes and its clinical markers , 19, eleConsistent with the lack of ethnic specific data on the association of IB with metabolic risk, there is also a lack of data on the possible contribution of IB to ethnic disparities in diabetes, elevated cholesterol and hypertension. Our findings suggest that IB may contribute to differences in, particularly, diabetes between the ethnic groups. If confirmed in larger studies among multiethnic populations, the potential implication is that reducing the burden of infections or timely initiation of treatment directed at diminishing or reversing its effects might contribute to reducing disparities between ethnic groups. The mechanisms by which IB works (e.g. epigenetic effects or inflammatory processes) should then be studied, as well as specific patterns of infections, currency and chronicity of infections and the association of these with incidence of metabolic risk factors. Unfortunately, the power of our study and availability of specific data limited a preliminary exploration of such specific patterns.First and foremost, the cross sectional design of our study poses a major limitation. The proposed implications should be read with caution, as causal inferences cannot be made. For example, previous work shows that diabetes might also cause impaired host defenses and thus predispose to infections , 42. AltThere are some further limitations that merit discussion. First, the overall response rate was relatively low (44%). However, we find it unlikely that selective response would change the interpretation of our findings as there were no significant differences between the respondents and the non-respondents in a previous analysis .Second, we did not distinguish between past and chronic infection, and the estimated IB may have been flawed by the definition of our measures. As indicated previously, IB was based on seropositivity to antibodies (mostly IgG). Several potentially relevant chronic infections were not measured. Additionally, IgG antibodies only indicate prior infection (or vaccination), and not current infection, chronicity or duration of infection . AdditioThird, as in many epidemiological studies, we partly defined our outcomes based on self-reported diagnoses, in line with previous analyses within the study population –5. This Finally, the results may have been affected by residual confounding. We were unable to adjust for potentially important factors, such as dietary intake, hygiene and (early life) living conditions in our analyses. In addition, numbers were too small to distinguish between generations. Moreover, we were not able to investigate whether treatment for infections (e.g. HCV ), the boIn conclusion, our study showed that Turkish and Moroccan adults in Amsterdam have a higher IB than Dutch adults and that a higher IB was associated with differences in metabolic risk factors, in particular diabetes. Due to the cross-sectional nature of the study, we cannot draw any conclusions with regards to the time-sequences of cause and effect. Nevertheless, the findings ask for further research into the nature of association of IB with metabolic risk factors in a longitudinal setting, including investigations of dose-response relationships and an investigation of possible underlying mechanisms leading to the incidence of metabolic risk factors for CVD. If the association and time-sequence are confirmed, a reduction in IB or treatment directed at effects of IB may possibly be investigated as a target for reducing ethnic disparities in metabolic risk factors.


AbstractChilocorini, Coccinellini, and Epilachnini. These tribes were chosen based on their relatively limited species diversity, as well as their large size and high colour diversity, making them easy to observe and collect. The identification key runs on Xper3 software, which allows the building of structured knowledge bases and online free-access keys. The online interactive Xper key is available at http://french-ladybird.identificationkey.fr.An identification key based on French ladybird colouration is proposed for the tribes  The identification of species is central in ecology, conservation biology, systematics, and related disciplines  . Europe If the identification of large and charismatic animals may be easy, the majority of organisms require expert skills for accurate identification and the inability to identify species represents a major challenge known as the Taxonomic Impediment . The mosCoccinellidae is a family of beetles popular and appreciated by naturalists and the general public. Because these animals have ecological and economic values as predators of pest insects , their identification may be of importance for naturalists, amateurs and professionals (http://www.harlequin-survey.org) and the Ladybird Survey (http://www.ladybird-survey.org) in the UK, the Lost Ladybug Project (http://www.lostladybug.org) and the Buckeye Lady Beetle Blitz (https://entomology.osu.edu/about-us/multimedia/buckeye-lady-beetle-blitz) in the US, and the Coccinula Recording Scheme in Belgium , and the identification is impossible if some characters are missing . Moreover, this type of keys cannot be modulated or adapted to various kinds of publics, environmental conditions, season, or geographical location.Most North American or European ladybird identification keys are single-access and difficult to use for non-specialists . Others IIK) are available online , but most of them are only digital versions of single-access keys and maintain the same difficulties for the user.Modern tools developed along with digital technologies and data processing make identification easier for the user. In this perspective, several interactive identification keys  of the specimen . The advThis study aims to i) release the first multi-access digital interactive identification key for French ladybirds based on colour that takes into account intraspecific variability; and ii) study and discuss the discriminating power of the characters: can we identify species by colour pattern only? What are the most discriminating characters?Chilocorini, Coccinellini and Epilachnini , or doubtful records . Platynaspisluteorubra Goeze, 1777  was also removed due to its small size (2.5–3.5mm). Since only a few discriminating characters are known that are not reliable with colour patterns, Henosepilchnaangusticollis Reiche, 1862 is not discriminated from its congener H.argus Geoffroy in Fourcroy, 1785 in the key.The current taxonomy  and the Muséum national d’Histoire naturelle, Paris, France (MNHN) and their data are available at https://science.mnhn.fr/institution/mnhn/collection/ec/search.Specimens were examined in the collection of the A list of 21 morphological characters based on colour and shape is defined, mainly from existing identification keys . The descriptors are the 21 morphological characters previously described. Some of them are consistent only if some conditions are true for another descriptor and these dependencies define a hierarchical structure of descriptors  if for one given descriptor there are no states of descriptors in common. For each descriptor the index value ranges between 0 (null discriminatory power of the descriptor) and 1 .The discriminatory power, which represents the quantitative assessments of the ability of a descriptor to distinguish taxa, is measured with the Xper original index  implemen3. For the comparison between genera, we estimated the number of discriminating characters, weighted or not by the number of colour forms. A subset of descriptors sufficient to discriminate the total of descriptors with the same efficiency was also calculated with the “minset” tool , four are parent descriptors  and 14 are child descriptors . Ninety-eight states are described .The consistency of the knowledge base has been tested with the “Checkbase” functionality of XperThe four most discriminating characters (XPER index >0.8) are the type of pronotum patterns (#5), the number of elytra markings (#8), and the number of lateral (#10) and longitudinal (#11) lines of elytra markings. These characters can separate taxa in 7 to 13 groups. For example, the two most discriminating characters (#5 and #8) split all the remaining taxa in 10–13 different groups including 2–13 taxa per group.Coccinellaseptempunctata and C.magnifica. Eleven descriptors are sufficient to separate all taxa . Despite its weak discriminating power, the character #21 is the only one that can distinguish the two species xa Table , in boldCoccinella , elytra with different markings, but always devoid of rim around the edge, short down hairs, cream rings around dots, or dark sutural band.Among the 21 characters, 12 are informative (in blue) whereas the other nine are constant and cannot discriminate within this genus (in red). The intersection column shows what is constant in Comparison between the 24 genera included in the study Table Coccinula (5% of discriminating characters), Henosepilachna (14%) and Chilocorus (19%); the most variable are Adalia (76%) and Harmonia (67%). If weighted by the number of described colour forms per genera, the most constant are still Coccinula and Henosepilachna; whereas the most variable genera are Ceratomegilla and Exochomus.Among the genera with at least two species studied, the most constant are Single-access identification key and comparison with standard keysEpilachnini species (in green). The same reasoning applies to Coccinella species (in red) with six different paths, and the colour forms of A.decempunctata (marked with a yellow star) with six different paths .www.spipoll.org), also built with Xper3.Most classical and single-access keys share characters that are quite difficult to observe for students, naturalists and the general public (e.g. for ladybirds in www.keytonature.eu) aims to develop new, more convenient and paper-free identification tools, for use within schools and universities across Europe and available on a variety of mobile platforms . However these keys are single access, e.g., MobileKey (https://www.vigienature-ecole.fr).Identification in the field is traditionally realised with paper-printed keys, but recent developments of mobile devices make it possible to use portable version of digital keys. In this perspective, the project “KeyToNature” . This kind of key aims to increase the curiosity of the general public, and to collect more data on the biology and distribution of species.Both experienced and inexperienced users are likely to succeed in identifying problematic species  if they


The placement of an implant in a previously infected site is an important etiologic factor contributing to implant failure. The aim of this case report is to present the management of retrograde peri-implantitis (RPI) in a first maxillary molar site, 2 years after the implant placement. The RPI was treated using an air-abrasive device, Er,Cr:YSGG laser, and guided bone regeneration (GBR).  A 65-year-old Caucasian male presented with a draining fistula associated with an implant at tooth #3. Tooth #3 revealed periapical radiolucency two years before the implant placement. Tooth #3 was extracted, and a ridge preservation procedure was performed followed by implant rehabilitation. A periapical radiograph (PA) showed lack of bone density around the implant apex. The site was decontaminated with an air-abrasive device and Er,Cr:YSGG laser, and GBR was performed. The patient was seen every two weeks until suture removal, followed by monthly visits for 12 months. The periapical X-rays, from 6 to 13 months postoperatively, showed increased bone density around the implant apex, with no signs of residual clinical or radiographic pathology and probing depths ≤4 mm.  The etiology of RPI in this case was the placement of an implant in a previously infected site. The use of an air-abrasive device, Er,Cr:YSGG, and GBR was utilized to treat this case of RPI. The site was monitored for 13 months, and increased radiographic bone density was noted. Retrograde peri-implantitis (RPI) is termed as a symptomatic periapical lesion, developed after implant placement, while the coronal portion of the implant remains fully osseointegrated . It was Etiological factors of RPI are divided to those which occur at the time of implant placement and those due to a preexisting disease  7–9]. M–9. M7–9]Bacteria can be encapsulated in edentulous areas, up to 1 year after the extraction . TherefoThe aim of this case report was to present the management of RPI in a first maxillary molar site, 2 years after the implant placement. The implant apex was located in close proximity to where the periapical radiolucency of tooth #3 was in 2013. The diagnosis was RPI, and the affected implant was treated successfully using the combination of an air-abrasive device, Er,Cr:YSGG laser, and guided bone regeneration (GBR).they said I have an abscess around my implant.” The patient had been prescribed clindamycin 300 mg for a week by his referring predoctoral student of the same University. Clinically, a draining fistula was present at the tooth #3 implant site, just apical to the mucogingival junction, measuring approximately 3 × 3 mm. Comprehensive periodontal and radiographic evaluations were performed. The patient was very meticulous with oral hygiene, and there was absence in bleeding on probing and mobility, with thick gingival biotype. The periodontal pocket measurements around the implant were ≤4 mm. The diagnosis associated with the implant at the area of tooth #3 was RPI.A 65-year-old Caucasian male, nonsmoker, ASA II with a significant medical history for hypertension, was referred in 2016 to the Graduate Periodontics Clinic at the University of Texas Health Science Center at Houston. His chief complaint was “The dental history of tooth #3 revealed periapical radiolucency in 2013, on the mesial buccal root , measuri37μm, RFPT5-14 mm, Biolase Technology, Irvine, CA)  . The lasine, CA)  and 19. ine, CA)  and 21. ine, CA) .Bacteria associated with failing implants due to infection are similar to those found in chronic periodontitis cases. Therefore, the disruption of the biofilm is a prerequisite for successful treatment , 21. AnyReiser and Nevins  suggesteTo date, there is no consensus for the treatment of RPI; therefore, the treatment is empiric. Romanos et al., based on a systematic evaluation of clinical case reports, showed that the use of antimicrobials only was not successful in any case for the treatment of implant periapical lesions . The useMohamed et al. presented a case report where a patient was referred for implant placement at the upper lateral incisor (#10) . Both, tQuaranta et al. presented a similar case report of an implant which was placed immediately in a postextraction socket . The extAtaullah et al. displayed a case where an endodontically treated central incisor (#9) had class III mobility, a post and core and a large periapical lesion . The autCase reports showed that RPI was diagnosed after immediate implant placement in a previously infected area , 27. The2); diode (810–980 nm); neodymium-doped: yttrium, aluminum, and garnet (Nd:YAG); erbium-doped: yttrium, aluminum, and garnet (Er:YAG); and erbium, chromium-doped: yttrium, scandium, gallium, and garnet  [Different types of lasers are available in surgical dentistry, in various wavelengths, such as carbon dioxide (COCr:YSGG) –34. DuriCr:YSGG) –34.2 laser helps avoid implant surface damage, and the temperature is not increased in critical levels [Azzeh, showed in a peri-implantitis case report that the use of Er,Cr:YSGG laser enabled the regenerative osseous surgery around an implant. In his case report, the laser was used for flap reflection, as well as for cortical perforations. The results were comparable to our clinical case report, achieving bone regeneration without any complications and with high patient satisfaction . Al-Falal levels , 38. On l levels .Schwarz et al. performed a controlled clinical study comparing Er:YAG versus mechanical debridement with chlorhexidine, in moderate and advanced peri-implantitis cases. The results in terms of reduction of PD and CAL were not significant at 12 months. The most interesting result of this study is that 12 months postoperatively, all patients were discontinued from the study and received further laser treatment and GBR. The reason for that decision was the increased BOP after 12 months of healing .To the best of the authors' knowledge, this is the first case report to describe the concurrent use of an air-abrasive device, Er,Cr:YSGG, and GBR for the treatment of RPI. Implant #3 was placed one year after extraction of tooth #3 and ridge preservation. The implant was placed according to the restorative needs of this site; however, the apex of the implant was positioned in the approximate location of the previous periapical radiolucency of the mesial buccal root of tooth #3. Even though no signs of infection or inflammation were present at the site before and/or after implant placement, RPI was diagnosed 2 years after the implant placement. Dahlin et al. suggested a more aggressive debridement due to the rough surface of the implants. The implants with rough surfaces create an environment where further progression of the RPI or peri-implantitis occurs. Our treatment was in accordance with this suggestion, with the use of an air-abrasive device and Er,Cr:YSGG. The aim of our approach was, due to limited surgical access, to avoid leaving any locus minoris, allowing the bacteria to nevertheless reside in the implant surface after the end of the surgical debridement phase . The subThe etiology of RPI in this case was the placement of an implant in a previously infected site. This case of RPI was treated through a surgical approach utilizing an air-abrasive device, Er,Cr:YSGG, and GBR. The site was monitored for 13 months, and increased radiographic bone density was noted.


Lifetime suicide attempts in patients with comorbidity between psychotic disorders and Substance Use Disorder (SUD), known as dual diagnosis, was associated with a worse clinical and cognitive state, poor prognosis and premature death. However, to date no previous study has examined the cognitive performance of these patients considering as independent the presence or absence of lifetime suicide attempts.We explore executive functioning differences between suicide attempters and non-attempters in dual schizophrenia (DS) patients and the possible related factors for both executive performance and current suicide risk. Fifty DS male patients in remission of SUD and clinically stables, 24 with and 26 without lifetime suicide attempts, were evaluated. We considered Z scores for all neuropsychological tests and a composite summary score for both premorbid IQ and executive functioning.DS patients showed low performance in set-shifting, planning and problem solving tasks. Those with suicide attempts presented lower composite summary scores, together with worse problem solving skills and decision-making, compared with non-attempters. However, after controlling for alcohol dependence, only differences in decision-making remained. Executive functioning was related to the premorbid intelligence quotient, and several clinical variables . A relationship between current suicide risk, and first-degree relatives with SUD, insight and positive symptoms was also found.Our results suggest that problem solving and, especially, decision-making tasks might be sensitive to cognitive impairment of DS patients related to presence of lifetime suicide attempts. The assessment of these executive functions and cognitive remediation therapy when necessary could be beneficial for the effectiveness of treatment in patients with DS. However, further research is needed to expand our findings and overcome some limitations of this study. Substance Use Disorder (SUD) is becoming more prevalent over the years and it is highly common in Schizophrenia (SZ), a comorbidity known as Dual Schizophrenia (DS). This dual diagnosis has relevant clinical implications, given that substance use could exacerbate the SZ symptoms  as well Around 20–50% of SZ patients will attempt suicide in their lifetime , 10. TheIn addition to the SUD, other risk factors for suicide described in SZ patients are: male gender, single marital status, living alone and social isolation, family or personal history of lifetime suicide attempts, aggressive behavior, depression and hopelessness, low stress resistance, higher insight and metacognition ability. Moreover, other factors are also linked to suicide risk in SZ patients: low adherence to non-pharmacological treatment, more typical antipsychotic prescriptions, long-term illness with several exacerbations, loss of faith in treatment, fear of deterioration, higher insight of the illness, increased positive and fewer negative symptoms, higher nicotine consumption and greater duration of untreated psychosis , 24, 25.On the other hand, the study of the clinical characteristics of the DS patients highlights the important role played by cognition. Compared with the single condition, in the DS it has been observed a worse global cognitive state  with a mTaking all the factors stated above into consideration, DS individuals are a vulnerable population to commit suicide, given that they meet many of the preconditions for the emergence of suicidality. However, few studies have evaluated the executive functioning of the DS patients and none has addressed its possible influence on the existence of lifetime suicide attempts and clinical variables that may be modulating results, so new research is needed to clarify these questions.The aim of this study was to explore, firstly, the executive functioning differences between suicide attempters and non-attempters in DS patients and the possible premorbid and clinical related factors. To do it an exhaustive clinical evaluation and a complete neuropsychological battery was applied, being all patients in remission of SUD and clinically stables.The participants were 50 DS male patients (36.06 ± 7.79 years) from seven medical centers in Barcelona. They were assigned to two groups according to the self-reported previous suicide attempts: DS attempters  and DS non-attempters . Our sample size was aimed to have a balanced design in two groups. Both groups were abstinent for at least three months, controlled by urinalysis.Patients were derived by medical centers from their diagnoses according to the DSM-IV-TR (2000)  and inclAll patients were in treatment for their clinical conditions (SUD and psychotic disorder) with an integrated intervention in which addiction and mental health intervention are offered at the same time and by the same team . IntegraThe ethic committee of the University of Barcelona approved this study, which complies with the ethical standards on human experimentation and with the Helsinki declaration of 1975, as revised in 2008. All participants provided written informed consent and were not compensated for their participation. Data collection was carried out between 2013 and 2015.Information was collected using the Structural Clinical Interview for DSM-IV-TR Axis I Disorders (SCID-I)  along wiAdditionally, the Clinical Global Impression-Severity scale (CGI-S)  was applWe used the Vocabulary and Block Design subtests (WAIS-III) as a reliable estimate of verbal and non-verbal premorbid IQ . To obtaηp2) statistic was used to measure the effect size, in conjunction with the observed power through the option available in the analysis of variance, and the post-hoc comparisons were Bonferroni corrected. Finally, we conducted stepwise linear regressions considering only the significant variables (p < 0.05) found in a previous bivariate correlation analysis for executive functioning and current suicide risk. In all cases the conditions of application and non-existence of collinearity and multicollinearity were verified. Data were analyzed using the Statistical Package for the Social Sciences .Group differences in demographic and clinical variables were explored with the Mann-Whitney U test (U) or with the Chi-Square test for categorical variables. If the quantitative data fulfilled the necessary conditions, the Student’s t-test (t) was used; when the conditions were not met, the nonparametric Mann-Whitney U test was used instead. Differences in Z scores of neuropsychological performance between groups were analyzed with one-way analysis of covariance (ANCOVA) for Vocabulary, Block Design, Backward Digits subtests, TMT-B and composite summary scores for both premorbid IQ and executive functioning. Multivariate analysis of covariance (MANCOVA) was conducted in the case of the ToH, WCST and IGT. Repeated measures multivariate analysis of variance (RM MANCOVA) was also used for the five blocks of the IGT direct scores. In all cases, we considered age as covariate to control for possible effects in cognitive performance because, although groups did not show differences, are known the age-related effects both in general population  and DS pχ2(1) = 1.82; p = 0.18), we have observed a tendency of higher proportions of patients with suicide risk in the DS+ (84.6%) compared to the DS- group (58.3%). Daily medication was equivalent between groups, except for use of interdictors, with higher consumption in the DS+ group. Moreover, DS+ showed a higher number of first-degree relatives both with SUD and psychiatric disorders, daily cigarette consumption and nicotine dependence compared to DS-. No significant differences were found between groups in psychotic symptoms (PANSS scores).Groups did not differ in sociodemographic data, medical comorbidity, CPZ, CGI, GAF, depressive symptoms, social adaptation, daily caffeine intake and current suicide risk scores see . AlthougRegarding SUD characteristics, polyconsumption was the more frequent pattern in the total sample (72%) and also in both groups (DS+: 83% and DS-: 61%). DS+ patients showed greater alcohol consumption than DS-, although the percentage of patients with the alcohol as primary drug of dependence was not different between groups. Moreover, the two groups did not show differences in length of abstinence, number of relapses, duration of SUD and severity of SUD (DAST-20).The total sample showed a low performance compared to the normative data in the TMT-B, reaction time in the ToH, and trials to first category in WCST (z scores lower to -1SD). In the other tasks, both in the individual components and global scores, as well as in the composite summary score of executive functioning, performance tended to be worse than average but in no case exceeds -1SD . < 2.229; p > 0.143; ηp2 < 0.049).The groups showed similar premorbid IQ, considering both the verbal component as the manipulative, and only provided differences in the performance of WCST and IGT. The WCST analyses showed significant worse scores for the DS+ patients in categories completed, trials to first category and in the global measure of WCST performance. However, these differences disappeared when the alcohol dependence was considered as a covariate in the analyses  = 11.274; p = 0.002; ηp2 = 0.193; power = 0.907)  = 5.203; p = 0.027; ηp2 = 0.100; power = 0.636), with a negative learning compared to the DS-  > 4.64; p < 0.037; ηp2 > 0.092; power > 0.562).Considering the IGT, we obtained significant differences in the third, fourth and last block trials as well as in the total score , with the DS+ group showing the worst performance. Although the Z scores for both groups in the IGT were within the mean, when the total direct scores were considered regarding the type of decision-making chosen, the DS+ group showed a disadvantageous pattern in comparison to the DS- (F 907) see . Similar DS- see . All sig = 4.982; p = 0.032; ηp2 = 0.096; power = 0.603).Finally, the composite summary score of executive functioning was worse in DS+ group as compared to DS- and it continued providing significant differences when in the analysis the alcohol dependence was included as covariate , in the DS- group premorbid IQ, DAST-20 and duration of SUD explained the 87% of its variance, while in the DS+ group IQ together with duration of SUD accounted for the 52% see . In all We found significant correlations between current suicide risk and number of first-degree relatives with SUD and insight, which accounted for 64% of the variance for the total sample. When considering the groups this result correspond to the DS+ patients, with first-degree relatives with SUD and insight together explaining the 87% of their variance for current suicide risk. In contrast, in DS- group the 47% of the variance of current suicide risk was explained for the positive symptoms (PANSS) .To our knowledge, this is the first study aiming to explore the executive functioning, current suicide risk and clinical state in DS patients, considering the presence or absence of lifetime suicide attempts and related factors.We did not find differences in any sociodemographic variables or in most of the clinical ones between DS+ and DS- patients. The only differences observed were that the DS+ group showed a higher number of daily cigarette intake and more nicotine dependence, greater rates of alcohol consumption and use of interdictors, which may be due to the need to relieve the dysphoric mood in these patients , 52, 53.The groups neither showed significant differences in current suicide risk scores, although we observed more patients in DS+ than in DS- group fulfilling the risk criteria. Regarding pharmacological treatment, the literature suggests that typical antipsychotics are more related to suicidality due to their side effects, while atypical antipsychotics reduce the rates of attempts . HoweverAlthough precedent studies about neurocognition in DS are heterogeneous, it has been observed that DS patients are characterized by a worse global cognitive state , which iWe want to note that the lack of differences in executive functioning in a SZ sample with or without lifetime suicide attempts found in some studies , 55 may Moreover, several factors modulate executive performance of DS patients. Thus, the severity of SUD seems to play a positive influence on executive functioning and specifically in planning abilities, in contrast to negative symptoms. The result of the DS- group indicates that this is probably due to the necessity to obtain substances to maintain drug use in subjects with a stronger addiction , 28, 31,Our results highlight the importance for the greater suicide risk score of having more insight and first-degree relatives with SUD in DS+, suggesting the hypothesis that these patients are more vulnerable to the perception of stigma, which increases the future probability of suicide attempts , 29. EveOur results emphasize the importance of taking into consideration the clinical and cognitive factors that modulate the suicidality in DS, in order to prevent future suicide attempts and to develop targeted interventions to reduce such risk, although further studies are needed to provide more consistent conclusions. The DS+ group presented worse general executive functioning, decision-making abilities and problem solving skills, although the last one was influenced by alcohol consumption. Several clinical factors, such as global psychosocial functioning, negative symptoms, SUD characteristics , and premorbid IQ modulated executive functioning in DS patients. Furthermore, first-degree relatives with SUD, insight scores and positive symptoms were positively associated with suicide risk scores. Our results can be not generalized, having to be taken with caution since it is the first study made in this line and it is not exempt of some methodological limitations. Future works should examine the therapeutic benefit of including neurocognitive remediation therapy when necessary in the integrated treatment of DS patients.


A few studies reported good correlations between signals from tumor tissues and CTCs or cfDNAs, making it possible to detect cancers using CTCs and cfDNAs. However, the detection cannot tell which cancer types the person has. To meet these challenges, we developed an algorithm, eTumorType, to identify cancer types based on copy number variations (CNVs) of the cancer founding clone. eTumorType integrates cancer hallmark concepts and a few computational techniques such as stochastic gradient boosting, voting, centroid, and leading patterns. eTumorType has been trained and validated on a large dataset including 18 common cancer types and 5327 tumor samples. eTumorType produced high accuracies (0.86–0.96) and high recall rates (0.79–0.92) for predicting colon, brain, prostate, and kidney cancers. In addition, relatively high accuracies (0.78–0.92) and recall rates (0.58–0.95) have also been achieved for predicting ovarian, breast luminal, lung, endometrial, stomach, head and neck, leukemia, and skin cancers. These results suggest that eTumorType could be used for non-invasive diagnosis to determine cancer types based on CNVs of CTCs and cfDNAs.With the technology development on detecting circulating tumor cells (CTCs) and cell-free DNAs (cfDNAs) in blood, serum, and plasma, non-invasive diagnosis of  Non-invasive detection of cancer is becoming possible with the development of technologies on capturing circulating tumor cells (CTCs) and cell-free DNAs (cfDNAs) in blood, serum, and plasma It is well known that there are multiple clones within a tumor, including a founding clone and several sub-clones Robustness is always the most important consideration in developing algorithms. To deal with this issue, methods based on the stochastic mechanisms have been developed. For example, multiple survival screening (MSS) has been developed to achieve robustness by screening random gene sets and random datasets and then selecting genes with higher probability of contributing to robustness. In cancer samples, these genes are often cancer hallmark-associated genes i.e., genomic amplifications) of the cancer hallmark-associated genes  using ada, considering that CNVs are often presented as discrete values and ada shows advantage in speed using the stochastic gradient boosting procedure. Furthermore, we also applied a combinatory signature set approach in eTumorType In this study, we developed a computational algorithm, eTumorType, by modeling CNVs in the founding clone (SNP 6.0 microarray data of tumors for 18 cancer types were collected from The Cancer Genome Atlas (TCGA) database . Given tThe segmentation files annotated based on the reference genome of hg19 were downloaded from TCGA. These files were used as inputs to the GISTIC 2.0 ABSOLUTE is used to identify aberrational chromosome segments involved in the founding clone or sub-clones in the tumor tissues There are three layers in the eTumorType algorithm : (1) buiThe cancer hallmark-associated genes were collected based on GO annotations of genes for cancer hallmarks P value of 0.01 based on Fisher’s exact test was set for statistical significance; (2) if the sample size of one cancer type is smaller than 200, but that of the other cancer type is larger than 200, the P value threshold was set to 0.005; (3) if the sample sizes of both cancer types are larger than 200, the P value cut-off was set to 0.001. Here the number of 200 was chosen considering the sample size distribution of the training sets for the 18 cancer types examined. For the eleven, three, and four cancer types, each contains >200, <100, and 100–200 samples, respectively. The DAGs were grouped based on cancer hallmarks they are belonging to. If a gene belongs to multiple cancer hallmarks, it was assigned to multiple gene groups. The selected genes annotated in the six cancer-hallmark GO terms were retained for the subsequent analysis. For each GO term, we ranked its genes based on the product of amplification degree and amplification difference between two cancer types . The top-30 and top-100 genes were tried for constructing models that classify the two cancer types using the ada R package Significant differentially amplified genes (DAGs) between any two cancer types were identified using fuzzy analysis clustering with R package on the training set. For a given pair of cancer types, the DAGs of each selected cancer hallmark were used to construct ada predictive models for discriminating cancer types. Considering the effect of sample size on the statistical significance and the expectation of sufficient DAGs, a composite approach was employed: (1) if the sample sizes of both cancer types are smaller than 200, a loose https://cran.r-project.org/web/packages/pamr/index.html). Finally, a cancer-type centroid matrix was created by pooling the centroid vectors for all cancer types together, which is 18 possible cancer types × 18 cancer types included in the training set . Secondly, the correlation coefficient between it and the centroid for each cancer type (the cancer-type centroid matrix) was calculated. Thirdly, the correlation scores for all possible cancer types were ranked; a higher ranking suggests a higher probability that the given sample might belong to that cancer type . In thisIn the training set, the average number of GO-ada models voting for a cancer type is likely to be high for some of the cancer types but low for some other cancer types ; S1–S4. Next, the weighted correlation analysis was performed. Briefly, a high  and low  weights were assigned to leading up-/bottom-patterns, respectively; the weight of 1 was set for the other cancer types. The setting of 3 for the leading up-patterns showed a relatively better performance on accuracy and power in the validation set . For the leading bottom-patterns, the performances for the various settings were similar. The results reported in this study were based on the weights of 3 and 0.1 for the leading up-patterns and leading bottom-patterns, respectively. Finally, the correlation scores were ranked and used for predicting cancer types.Eighteen common cancer types containing 5327 samples from TCGA were included in this study . CNVs ofi.e., voting profile). For a given cancer type, we averaged the voting numbers of each cancer type for the voting profiles of all the samples of that cancer type. We found that the average numbers of GO-ada model voting for cancer types were very similar among the training, validation, and test sets for each cancer type  for the samples in the validation and test sets. A sample could be predicted to a set of cancer types (see Method). When considering the top-1 cancer type alone, only five cancer types were observed with accuracy of ≥0.80 in the validation set, but none in the test set . When coThe centroid-based correlation prediction showed that some cancer types had similarity, leading to the failure of ranking in top 1, which could be taken into account to shrink down the cancer type possibilities and then able to improve prediction. For example, the LUSC samples got higher numbers of GO-ada models voting for OV, LUAD, HNSC, and LUSC, but very lower votes for THCA and LAML . This reBy applying the leading pattern-weighted correlation prediction, the prediction performance was significantly improved . For somIn summary, the prediction performances for the cancer types of COAD/READ, GBM, brain lower grade glioma (LGG), prostate adenocarcinoma (PRAD), and KIRC were increased significantly, from 0.85 to 0.92 and from 0.83 to 0.87 on average for accuracy and power, respectively, in the training set. The corresponding increases in the test set were from 0.81 to 0.90 and from 0.82 to 0.86 on average for accuracy and power, respectively. In the validation set, the prediction performances for the cancer types of OV, LUMINAL, LUAD, LUSC, uterine corpus endometrial carcinoma (UCEC), STAD, HNSC, LAML, and SKCM were increased moderately, from 0.80 to 0.84 and from 0.74 to 0.79 on average for accuracy and power, respectively. For the test set, the accuracy and power on average were from 0.77 to 0.83 and from 0.72 to 0.76. In total, these cancer types accounted for 14 of 18 types analyzed in this study. Therefore, the leading pattern-weighted correlation is able to discriminate cancer types.e.g., CNV, mutation, microRNA, methylation, and gene expression) associated with specific cancer types eTumorType integrates the traits favoring robustness including cancer hallmarks composed of DAGs, stochastic algorithm of ada, voting mechanism based on the screening of cancer type comparisons, and a further centroid generation. For a given cancer type, the centroids of average number of GO-ada voting for each cancer type were stable across the training, validation, and test sets. In general, eTumorType performs well in the predictions. The current predictive models have been constructed based on the 18 common cancer types, because they have relatively larger sample sizes in TCGA. For other cancer types, when their sample numbers get large enough, we will refine our models to include them in the future. This is the limitation of the current predictive models. However, eTumorType is capable of discriminating cancer types, which is beyond the current studies on CTC or cfDNA data, as the majority of these studies only focused on finding features (The number of input genes affects the performance of GO-ada voting. When using the top-30 genes, the predictions for OV, LUAD, COAD/READ, GBM, KIRC, HNSC, and LAML samples had relatively good performance with the accuracy of 0.87 and power of 0.81 on average in the validation set and the corresponding values in the test set were 0.86 and 0.76. On average, the leading pattern-weighted correlation method led to prediction accuracy and power of 0.78 and 0.73 for all cancer types in both the validation and the test sets, which were around 4% and 6% less than the predictions using the top-100 genes.In general, inclusion of the leading patterns improved the prediction. However, there was trade-off between accuracy and power when predicting some cancer types. This could be attributed to the inaccurate selection of the leading patterns. In our future work, we will improve the accuracy of selection and investigate the weights of the leading patterns in favor of reducing the trade-off.Previously, we suggested that genomics and systems biology research should be conducted at sub-clonal and founding clonal levels Many studies have focused on somatic mutation-based biomarker discovery for cancer detection. However, somatic CNVs may have advantages as they have strong signals Non-invasive cancer biomarker discovery has been studied on CTCs and cfDNAs in blood, serum, and plasma. Studies have reported similarity of CNVs in CTCs and cfDNAs with primary tumors In this study, we developed eTumorType, which enables the identification of cancer types for CTCs or cfDNAs in blood, based on CNVs in the tumor founding clone. This application could be used for the early detection of 18 common cancers. The approach of using the tumor founding clone, in which genomic changes will be carried onto every cancer cells of the tumor, helps us to capture the most important genomic variations for that tumor. The cancer hallmarks considered in eTumorType allow capturing the genomic variations which are most likely to be associated with cancer development and progression, thereby contributing to robustness. Furthermore, to improve the prediction performance of eTumorType in clinical diagnosis, we developed a leading pattern-correlation method, which increased the prediction accuracy and power. The analysis performed in 5327 tumor samples of 18 cancer types provides a reliable evaluation of the algorithm. We hope eTumorType prediction would shed light on non-invasive early diagnosis of cancer types in the future.EW conceived the idea and supervised the study. EW and JZ designed the algorithm. JZ implemented the algorithm and performed the analysis. JZ and EW analyzed the results. JZ drafted the manuscript and EW edited the manuscript. Both authors read and approved the final manuscript.The authors have declared that no competing interests exist.


To determine the prevalence and risk factors for pterygium in the adult Korean population of South Korea.Data were analyzed from 9,193 participants who were 40 years of age or older from the Korea National Health and Nutrition Examination Survey (KNHANES), conducted from 2009 to 2010. Standardized slit-lamp examinations were performed by study ophthalmologists to examine the anterior segment for evidence of pterygium. Pterygium was graded clinically as T1 (atrophic), T2 (intermediate), or T3 (opaque). Every participant underwent ocular and systemic examinations, as well as interviewer-administered questionnaires. Any evidence of pterygium and observed association between the risk factors were recorded.The mean age of the subjects was 55.7 (±0.2) years. Of the 9,193 eligible subjects, 935 had pterygium in at least one eye. In a multivariate logistic regression analysis adjusted for age and sex, pterygium was significantly associated with rural vs. urban residence , lower level of education , low income , smoking , and more hours of sun exposure . After adjusting for all variables, the prevalence of pterygium was significantly associated with age, sex, residence, education level, and smoking.This is a nationwide epidemiologic study in South Korea to assess the prevalence of and risk factors for pterygium. The overall prevalence of pterygium was 8.8% among Koreans aged 40 years or older. Older age, male gender, rural residence, lower level of education, and non-smoking were associated with the development of pterygium. It is well known that pterygium is one of the most common eye diseases. It is an abnormal, proliferative overgrowth of fibrovascular tissue which develops from the bulbar conjunctiva in the cornea. In advanced cases, it can induce significant astigmatism and decrease visual function caused by loss of corneal transparency ,2. AccorThe prevalence of pterygium has been reported in several population-based studies -20. The This study aims to examine the national prevalence of pterygium in an adult Korean population of Korea, based on survey data which is obtained from the KNHANES, and to try to analyze the risk factor which is associated with the occurrence of pterygium.The study of the prevalence of pterygium is based on a population-based survey on eye diseases by the KNHANES during 2009 to 2010. The KNHANES is a population-based, cross-sectional epidemiological survey of Korea which has been performed since 1998. 4,000 households in 200 enumeration districts were annually selected by the panel to represent the general Korean population by using a multistage clustered and stratified random sampling method that was based on the data from the 2005 National Census [Each participant had a comprehensive vision and eye examination, which included: presenting and best-corrected visual acuity, auto-refraction, and slit-lamp examination. A structured slit-lamp examination  was done by trained ophthalmologists in order to examine the anterior segment for evidence of pterygium. The diagnosis of pterygium was made clinically, and it was defined as a radically oriented fibrovascular lesion crossing over the nasal or temporal limbus. Grading was based on the visibility of the underlying episcleral blood vessels . T1 (atr2). Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by standard methods using a sphygmomanometer with the patient in a sitting position. The SBP and DBP readings were twice recorded at five minutes intervals and were averaged for in this analysis. Blood samples were obtained after fasting for 12 hours in the morning. Biochemical markers like fasting plasma glucose, total cholesterol, triglycerides, and high-density lipoprotein cholesterol were measured. Diabetes mellitus (DM) was defined as a fasting plasma glucose level above 126 mg/dL, and/ or treatment with oral hypoglycemic agents or insulin. Hypertension was defined as an SBP over 140 mmHg, and/or DBP over 90 mmHg, or by a self-reported current use of antihypertensive medications. Hypercholesterolemia was defined as total cholesterol over 200 mg/dL.A detailed interviewer-administered questionnaire was deployed to collect relevant sociodemographic and medical information. Collected data included the information such as marital status, education, occupation, current housing status, lifestyle, eye symptoms, past medical and surgical history, and family history of eye disease. Education level was categorized into four groups: elementary school or less, middle school, high school, and college/university or more. The revised household income was calculated from the total household income divided by family size. A participant was considered to be a ‘drinker’ if he or she drank more than once per month over the past year. Smoking status was divided into two groups: smokers and non-smokers. Non-smokers indicate people who have never smoked or have smoked less than five packs in their lifetime. Height and weight were obtained using standardized techniques and equipment. Body mass index (BMI) was calculated as the ratio of weight to the square of height (kg/mContinuous variables were described as mean±standard error (SE), while discrete variables were expressed as numbers and percentages. Differences in categorical data were analyzed by using the chi-square test. The relevance of all variables and the risk factors of pterygium were estimated by the odds ratio (OR) and its 95% confidence intervals (CI). Multiple logistic regression models were used to evaluate the independent effects of the variables on the risk factors for pterygium. Statistical analyses were performed with complex-samples analysis procedures in SPSS version 18.0 . We used the KNHANES stratification variables and sampling weights designated by the Korea Centers for Disease Control and Prevention (KCDC). All data of p<0.05 was considered statistically significant.The social and demographic characteristics of the participants are summarized in p=0.003) , which was consistently higher in male compared with female subjects (p=0.003) .p=0.01, respectively). In contrast, a significant increasing trend was not found in the prevalence of grade T3 pterygium with increasing age. In all three groups, significant sex difference was not found according to the grade of pterygium.Of the 935 subjects having pterygium in either eye, 449 subjects were categorized as having grade T1, 361 subjects had grade T2, and the rest 123 subjects had grade T3 . An incrThe results of univariate and multivariate logistic regression analysis are presented in The prevalence rates of pterygium reported in different studies vary greatly from 2.8% to 33.0% -16,19,20The previous studies -28 showeThis study also confirms that age was an important factor for the formation of pterygium, which is accords with the findings of many previous researches -15,17,18Although it is difficult to quantify the true amount of one’s exposure to sunlight with ultraviolet radiation, many studies have shown that outdoor workers have a higher risk of the development of pterygium, with cumulative exposure to ultraviolet radiation ,13,16-18In this research, smoking was protective against pterygium. Other studies also showed that smokers were less likely to have pterygium in other studies as well ,9. How sSeveral population-based studies demonstrated an association between the development of pterygium and higher blood pressure and total cholesterol level ,30. PeirThis study is the first epidemiologic study that has investigated the prevalence of pterygium in Korea based on the nationally representative data from a government-sponsored survey. The strengths of this survey is that it includes its nationwide, large sample size with standardized ocular assessment by ophthalmologists, using an objective method of grading pterygium and comprehensibly assessing associated factors. Our research revealed that significant racial/ethnic variations may exist even within a single Asian country. Our study may contribute to provide further insights into etiology, ethnic differences and the impact of pterygium on public health in Korean population. Despite of these strong points, our study has some limitation in explaining sunlight exposure models in detail and in cumulating occupational history. In the Barbados Eye Study, using sunglasses and prescription glasses can lower frequency of pterygium . PresumaOur attempt is the first nationwide epidemiologic study which has been conducted by both the Ophthalmologic Society and government organizations. This method proved powerful in investigating the national prevalence of disease conditions. Relation to pterygium with older age, males, and rural vs. urban residence, lower levels of education, and nonsmoking were also found. These results may allow ophthalmologists and nurses to counsel patients about potential modifiable risk factors.


The aim of this study was to determine if altered levels of selected trace elements manifest themselves during chronic depression. To identify elements strongly associated with chronic depression, relationships between the elemental contents of hair and nails and the interelement correlations were checked. Inductively coupled plasma mass spectrometry and ion chromatography were used to evaluate the contents of Zn, Cu, Co, Pb, Mn, and Fe in hair and nail samples from a total of 415 subjects . The study included logistic regression models to predict the probability of chronic depression. To investigate possible intercorrelations among the studied elements, the scaled principal component analysis was used. The research has revealed differences in TE levels in the group of depressed men and women in comparison to the healthy subjects. Statistically significant differences in both hair and nails contents of several elements were observed. Our study also provides strong evidence that the intermediary metabolism of certain elements is age- and gender-dependent. Zn, Mn, Pb, and Fe contents in hair/nails seem to be strongly associated with chronic depression. We found no statistically significant residence-related differences in the contents of studied elements in nonoccupationally exposed patients and healthy subjects. Depression is a very common condition in the general population, and it has serious health implications. According to the World Health Organization (WHO), 350 million people worldwide are affected by depression  and majoRecently, numerous studies have provided valuable information regarding the involvement of essential chemical elements in psychiatric disorders , 8. AccoAnalysis of TE in human tissues belongs to the challenges of today's analytical and clinical chemistry . Such anInductively coupled plasma mass spectrometry (ICP-MS) is the most versatile technique for determination of trace elements , 23. IonThe primary objective of this study was to evaluate the content of zinc, copper, manganese, iron, cobalt, and lead using optimised sample preparation method and two validated analytical methods . Both essential and toxic TE contents were evaluated in patients diagnosed with depressive disorder and compared with healthy subjects. We aimed to determine whether TE levels could be factors that significantly influence the risk for the development of depression in humans. An attempt was made to identify relationships between element content in hair and nails and interelement correlations to identify the elements and matrices that can be further used for the biological monitoring of depression. We also aimed to compare the content of selected trace elements in the samples taken from two populations coming from different geographical regions, that is, from Taiwan and from Poland.Although many papers exist on toxic metals and microelements in human health and disease, studies on elements and patients suffering from persistent depressive disorder are sparse. Our study provides new data on toxic and trace elements that are associated with depressive disorders. We present here the studies replicated in two independent laboratories, what is more, with the use of two different analytical techniques, involving patients with the same disorder but coming from different geographical locations.Our studies have been carried out in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans. The study protocol was reviewed and approved by the Ethics Committee of the Medical University of Lublin, Room 128, Al. Racławickie 1, 20-059 Lublin, Poland, and Homu Clinic, No. 61, Dongping Rd., East Dist., Tainan City 701, Taiwan (KE-0254/293/2013). persistent depressive disorder : 0.15 ml/minµl  Sample loop: 25   Temperature: 25 ± 1°C  Operating pressure: 1900 psi  Number of replicates: 3ICP-MS  RF Power: 1125 W  Plasma gas flow: 15 l/min  Nebulizer gas flow: 0.76–0.79 l/min  Auxiliary gas flow: 1.15 l/min  Nebulizer: cross flow  Plasma Torch: quartz  Sample flow: 1 ml/min  Scanning mode: peak hopping  Dwell time: 100 ms  Sweeps/reading: 20  Number of replicates: 3The detection limits were calculated as the average of six blank sample signals plus three times (and ten times for the limits of quantification) standard deviation of the signals obtained from blank samples. An acidified water sample was used to prepare calibration standards and dilution of all solutions and real samples. To assess the accuracy of the methods, the following certified reference materials were used: CRM NIES number 13 human hair and SRM 1643e-trace elements in water  Gaithersburg, MD, USA). Statistical analysis was carried out using R 3.1., an open source software using built-in routines and “rpart” package .The normality of results was checked by the Shapiro-Wilk normality test. Almost all variables exhibited significant  deviance from normality, except for Cu content in nails. The distribution of the results was significantly positively skewed, which was confirmed by D'Agostino test for skewness under the null hypothesis of normality.The correlation of elements' content with age was done by the Pearson correlation coefficient with the appropriate test for significant correlation. No significant correlations were found between element contents and age. The Spearman coefficient with the test gave consistent results.p = 0.017), Cu (p = 0.0016), Fe (p = 0.024), Mn (p = 2.7e − 05), and Zn (p = 2.8e − 08), and for content in nails, namely, Cu (p = 0.0072), Fe (p = 1.2e − 08), Mn (p = 1.4e − 05), Pb (p = 0.0020), and Zn (p = 2.4e − 06).The univariate difference of TE levels between healthy volunteers and patients (for each element separately) was checked using the Wilcoxon test. Significant differences were found for the elements' content in hair, namely, Co (p = 0.0025), Cu (p = 0.00021), Zn (p = 0.042) in hair and Co (p = 3.1e − 06), Cu (p = 0.00095), and Fe (p = 0.032) in nails. To investigate the possible interactions between depression, gender, and age, the appropriate linear models were built. These models applied the content of each element as modelled variables, whereas age, gender, and depression were used as predictors. The possible interactions were as follows: gender-age , gender-depression (cross-difference in content level), and depression-age (difference in slope between the control and studied groups). Despite confirming earlier conclusions found by the Wilcoxon test, the following interactions were found: (i) For Fe content in hair, a significantly different dependence of element content on age between genders was found (p = 0.016); the content slightly increased with age in women, whereas it decreased with age in men. (ii) Significantly lower levels of elements in healthy men (gender-disease interaction) were found for content in nails of Co (p = 0.018) and Cu (p = 0.0021). The opposite behavior  was found (but significant at 90% level only) for the content in nails of Zn (p = 0.030). (iii) Depression caused a significantly lower increase with age for Fe content in hair (p = 0.025).In an analogous manner, such differences between genders were tested. The content was found to be significantly different between genders for the elements Co  were different. The test compared all possible pairs of means, that is, for depressed women, depressed men, healthy women, and healthy men. In hair, we found that cobalt in female group with depression was significantly decreased when compared to control group and depressed men. The opposite result was found for copper in hair . For iron and lead in hair there were no significant differences among each group, whereas for manganese and zinc significantly different contents were found between both control groups and between studied groups. In nails, significant differences between both sexes  were identified for cobalt. For copper in nails significant differences were found between healthy men and other groups. Iron content in nails was significantly different between each healthy and each studied group (higher in the group with depression), content of manganese in nails was significantly higher in group with depression, content of lead in nails was significantly different between healthy men and depressed men, and zinc content in nails was significantly different in each group (the lowest content was found in depressed women).Figures To investigate possible intercorrelations between elements, scaled principal component analysis was used. This data mining method treats all patients as points in multivariate space and tries to find an angle of a two-dimensional plane  to represent the highest variance of the data. Projection onto this plane, understood as a “shadow” of the points, is the best possible representation of objects (patients) on a two-dimensional plot. However, the quality of the two-dimensional representation depends on structure of the data; that is, the more the intercorrelations, the better the ability to compress. Only 18% of total variance was explained by the two first principal components. This proves that the levels of elements are very independent and it is difficult to find any multivariate intercorrelations or visible trends in these data. The subjects had no tendency to be clustered. The lack of intercorrelations can be proven by investigation of loading vectors, that is, the projection of original axes onto the two-dimensional plane found by the analysis. In this case, loading vectors were randomly and uniformly distributed in all directions.n rows (subjects) and p columns (elements) and a column vector y containing 1 value for depression and −1 for control, the method tries to find an estimator for predicting this y vector from X. This estimator is then used for further prediction, and negative y means healthy, whereas positive indicates depression. In the case of multidimensional and intercorrelated data, it is the natural choice to use PLS regression instead of the classical one.Next, the multivariate discriminant models (equation differentiating persons with and without depression) were created with scaled PLS-DA  for hair, nails, and the total dataset. This method is analogous to the LDA  but instead of ordinary least squares regression uses the PLS  regression. Having a matrix, containing The complexity of two PLS factors was chosen with cross-validation in all cases. In the case of hair, seven healthy persons were misclassified as sick and two persons with depression were misclassified as healthy. In the case of nails, five healthy persons were misclassified as sick and two persons with depression were misclassified as healthy, respectively. A total model resulted in the misclassification of two and one persons, respectively. The estimators of PLS-DA model are shown in To obtain a formula for depression probability prediction, a logistic regression was used with stepwise variable selection against the Akaike information criterion (AIC). Three separate models were built and found: for hair, nails, and the augmented dataset. All of the methods detected similar variables, and this finding additionally confirms that these elements may, in fact, be relevant for chronic depression. It should be noted that the results do not predict the severity of depression.From our study, it is clear that there is a statistically significant difference in TE content of hair and nails between the depressed patients and the healthy subjects. It is important to take into consideration that all the participants were not on any special diets. Obviously the regular diet was different in the two countries, but the trend in altered trace elements profile was significant for dysthymic patients, regardless of their place of residence. It may suggest that not only nutritional factors are responsible for altered levels of investigated elements in hair and nails of dysthymic patients. Our findings may indicate a possible relationship between chronic depression and deficiency or excess of some TE as well as alterations in their metabolism.The lack of strong correlation between TE contents and place of residence of our participants and similar trend in alteration of TE content in chronic depression indicate that trace analysis may serve as a useful tool for the purposes of prevention .Zinc deficiency can lead to numerous complications such as stunted growth, diarrhoea, impotence, hair loss, eye and skin lesions, impaired appetite, and depressed immunity. Some cross-sectional studies associate a low Zn intake with depression in women , 29, whe2+ and Mn3+ can react with dopamine to create reactive oxygen species, which is known to cause damage to the dopaminergic neurons [Certain studies imply that relatively low amounts of Mn exposure could affect mood because even low levels of exposure result in neuropsychological effects . The iss neurons . The exa neurons . It is k neurons . Fe is r neurons . It was  neurons . Accordi neurons  depressi neurons . Our stuThe mechanisms of Pb neurotoxicity and the effects of Pb on neuronal death, on intraneuronal regulatory mechanisms, on neurotransmission, on transmitter release, and on transport of thyroid hormone have been studied extensively . IndirecAs for the other elements that were quantified in our study, although no strong associations were found between their content and the prevalence of depression in the patients studied, it should be noted that our results found an increase of Cu in both types of samples. This observation is consistent with data of studies undertaken by Ghanem et al. . Cu is iThe observed associations could provide insight into the etiology of depression, helping generate new hypotheses for further research and perhaps contribute to future healthcare planning. We realise that there is a need of a speciation analysis in relation to certain elements determined in biological matrices because various chemical species can indicate different biological effects. Unfortunately, some sample pretreatment procedures interfere with speciation studies, and therefore the final determination refers to “total” TE concentration in hair or nail samples. The ideal analytical strategy in which all species of all elements are determined simultaneously followed by the same pretreatment procedures still does not exist .Our studies have important strengths, for example, application of the most suitable analytical techniques taking into account the complexity of samples' matrices. These techniques were evaluated with the appropriate reference materials to ensure high quality of the entire analysis. Moreover, in our study we used two analytical techniques which allowed us to perform a multielement determination, including Fe, which is usually underestimated in ICP-MS studies.56Fe (40Ar16O+ and 40Ca16O+) and 57Fe . The interferences caused by 40Ar16O+ and 40Ar16O1H+ on 56Fe and 57Fe, respectively, may be reduced by using a shield torch, which unfortunately can produce other polyatomic interferences [The determination of Fe by ICP-MS is not recommended, especially in samples with complex matrices because of polyatomic interferences from different isotopes produced by O, Ar, and Ca on ferences . The nexWe present the associations between hair and nail TE status after age and gender adjustments, and the exclusion criteria of our study limit additional factors (variables) that may affect the content of TE. Patients with other psychiatric pathologies were excluded in our study. Neither the participants nor the persons conducting the experiment had access to key information that could interfere with or influence the results.There are different methods of analysis currently in use with different procedures used to collect and prepare samples. Widely divergent reference ranges are reported for the normal individual depending on which method of analysis is used, making it difficult to compare the results between different studies. External contaminants pose a significant concern and the proper pretreatment of samples should be used to limit such possibilities. There are a variety of factors that affect the content of TE in hair/nails in and of itself, namely, age, gender, diet, hair type, location of hair, and so forth. Despite these limitations, TE analysis of hair and nails remains an area of continuing interest and active research. However, the analytical data obtained must be interpreted with caution and forethought.Despite a growing number of studies undertaken in the field of TE determination in various disorders, the role of TE in depression has not been thoroughly elucidated. A reliable analysis of easily accessed samples of hair/nail could provide an answer to the still unsolved question of whether deficiency of certain elements or excess toxicity of other elements manifests itself during depression. Mutual interactions between elements in this disorder should also be taken into consideration for useful diagnostic information.p = 0.016); the content slightly increased with age in women, whereas it decreased with age in men. Significantly lower levels of elements in healthy men were found for content in nails of Co (p = 0.018) and Cu (p = 0.0021). The opposite behavior  was found (but significant at 90% level only) for the content in nails of Zn (p = 0.030). Depression caused a significantly lower increase with age for Fe content in hair (p = 0.025). The content of TE was found to be significantly different between genders for the elements Co (p = 0.0025), Cu (p = 0.00021), and Zn (p = 0.042) in hair and Co (p = 3.1e − 06), Cu (p = 0.00095), and Fe (p = 0.032) in nails. We found no statistically significant residence-related differences in the contents of Zn, Cu, Co, Mn, Fe, and Pb in nonoccupationally exposed patients with chronic depression and healthy subjects.The results of this study indicate various significant dependence between TE levels, the sample type, age, and gender. Zn, Mn, Pb, and Fe contents in hair/nails seem to be strongly associated with chronic depression. Further cohort studies could be useful in definitely elucidating whether TE are good predictors for the development of depression or whether depression's metabolic influences are the cause of changes in TE levels. The significant elevation in the concentration of manganese and significant decrease in the concentration of zinc were observed in the hair and nail samples of depressed patients. For Fe content in hair, a significantly different dependence of element content on age between genders was found (