Patients with skull base chordomas have a poor prognosis, and the role of the protein expression of brachyury in chordomas remains to be fully elucidated. The present study used immunohistochemistry to analyze 57 cases of skull base chordoma, and analyzed the clinical data of the patients. The results demonstrated that the protein expression of brachyury was negative in 8.8% (5/57) of the cases. The weak/positive, positive and strong/positive rates were 5.3% (3/5 7), 21.1% (12/57) and 64.9% (37/57), respectively. The association between the expression of brachyury and recurrence was not statistically significant. Kaplan-Meier analysis revealed that the degree of surgery, rather than the expression of brachyury, was associated with tumor recurrence (P=0.001). In conclusion, the results of the present study demonstrated that the expression of Brachyury offers a sensitive marker, but not a risk factor, for skull base chordomas, and radical surgery is recommended. Chordomas are rare, low-grade malignant tumors, which are derived from the notochord ,2. The pBrachyury is among the most common protein observed during analyses of chordomas. Brachyury is a protein encrypted by the T gene, which is located at 6q27 and is a relatively well-conserved gene , particuHowever, not all chordomas express the brachyury protein. Previous data have revealed that the brachyury protein is positively expressed in 75.64–100% of chordomas –13, and A total of 57 skull base chordoma samples were obtained from patients between May 2008 and May 2013 in the Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University . All cases were confirmed pathologically using traditional hematoxylin and eosin (HE) staining and cytokeratin, S-100, vimentin and epithelial membrane antigen staining. This procedure was performed according to the guidelines of the Department of Neuro-Pathology, Beijing Neurosurgical Institute . All clinical data , and magThe chordoma specimens were collected immediately following surgical resection without electrocoagulation. For storage, 10% neutral formalin solution  was used. All specimens were subsequently embedded in paraffin within the first week. HE staining was performed prior to brachyury protein staining on 3 mm slices of the specimens. The rabbit polyclonal antibody for brachyury H-210 , which is an antibody raised against amino acids 226–435 of the human brachyury gene was used for immunohistochemical staining. The streptavidin-peroxidase two-step method was performed under the direction of the HRP-DAB Substrate Chromogenic Reagent kit  Co., Ltd, Beijing, China).Brachyury-positive samples were defined as those exhibiting nuclear staining, and the brachyury staining patterns were categorized into the following four groups, as previously described : 0, no nThe surgical degree was confirmed by the senior surgeons and postoperative MR and CT images as follows: i) gross total resection: no residual tumor detected on the postoperative MR and CT images, as well as during the surgeon's observation under the microscope during surgery; ii) subtotal resection: residual tumor at <10% of the original volume; and iii) partial resection: residual tumor at >10% of the original volume. Gross total and subtotal removal were defined as radical resection. Tumor recurrence was defined as any newly identified enhancement following gross total resection or any increase in the tumor volume following subtotal resection.2 tests were performed using SPSS 12.0 software . P<0.01 was considered to indicate a statistically significant difference.The clinical data and follow-up data were collected using Epidata 3.02 database software . The groups with different expression levels of brachyury and other clinical risk factors were compared. Kaplan-Meier and COX survival analyses, and χThe 57 patients were all pathologically confirmed to have skull base chordomas. Of these patients, two were confirmed to exhibit chondroid chordoma and the remaining patients exhibited classic chordomas. The male to female ratio was 1:1.03 (28:29) and the mean age was 35.7±13.0 years . Of the 57 cases, 11 were cases of recurrent skull base chordoma, whereas 46 of the cases were present in untreated patients. The tumor volumes ranged between 5 and 168 ml , and surgery was performed by senior neurosurgeons, predominantly via the lateral approach. Overall, 20 patients underwent total tumor resection, 29 patients underwent subtotal resection and eight patients underwent partial tumor resection. Several complications were observed during the post-operative period. A number of patients required tracheotomies and received antibiotic treatment for intracranial (15 patients) or pulmonary infections (2 patients), and one patient died due to untreatable pulmonary infection following complete tumor resection and tracheotomy.During the average follow-up time of 19.6 months , 10 patients succumbed to illness, of which one patient exhibited pulmonary metastasis and undergone surgery three times prior to admission to the Department of Neurosurgery, Beijing Tian Tan Hospital. Among the 11 cases of recurrent skull base chordoma, five patients succumbed to illness, eight of which  were due to tumor recurrence or metastases. There were 18 cases of recurrence following surgical treatment in the Department of Neurosurgery, and the mean recurrence period was 9.9 months .All 57 cases were stained with brachyury, of which two chondroid skull base chordomas exhibited staining of 2+ and 3. The results of the staining demonstrated that five cases were negative for staining (8.8%), three cases exhibited weak positive staining (5.3%), 12 cases exhibited 2+ positive staining (21.1%) and 37 cases exhibited 3+ strong positive staining (64.9%), as shown in The age of the patients , expression levels of brachyury, gender, disease state (primary or recurrent), tumor volume , degree of surgical removal  and presence or absence of post-operative radiotherapy were analyzed using the COX multiple survival test (data not shown). The results revealed that the degree of surgery was the only risk factor that was associated with recurrence and survival rate . The Kaplan-Meier survival analysis confirmed that the surgical degree was associated with recurrnce . However, the results demonstrated no association between the expression of brachyury and recurrence in any of the three degrees of surgical removal ; P>0.05.The two cases of chondroid skull base chordomas were primary cases with a follow-up of 13 months, and they exhibited were high on the follow-up Karnofsky performance scale, without recurrence (90/100).Skull base chordomas are derived from remnants of the notochord and are often observed between the third and fifth decade of life, without notable gender predominance –2. Skullet al (et al (et al (The present study demonstrated that the brachyury protein was expressed in 91.2% of skull base chordomas. This was higher, compared with the expression level reported by Zhang et al . in whicl (et al  reportedl (et al , with hil (et al , revealel (et al .in vivo (et al (Brachyury acts as a key factor for the epithelial to mesenchymal transition of human carcinoma cell lines and promotes the metastatic dissemination of human tumor xenografts in vivo . The proin vivo ,8,12. Itin vivo  and coloin vivo . The brain vivo , howevero (et al  revealedet al (et al (In the present study, not all the cases were brachyury-positive. In addition, among the patients with a brachyury-positive tumor, brachyury-negative tumor cells were present, as shown in et al  reportedl (et al  revealedl (et al –4, the cl (et al ,12–13. Cl (et al ,19,21, rIn conclusion, the present study, which investigated 57 cases of skull base chordoma, demonstrated that the expression of brachyury can be used as a sensitive marker, rather than as a prognostic factor. However, the degree of surgery is a prognostic factor for skull base chordomas, and radical surgery is advocated. Further investigations are required to determine the regulation of the expression of brachyury.


This review tackles the issues related to disease burden caused by cervical cancer (CC) and its precursor (CIN) lesions in Brazil. A special focus is given to new technologies with potential to interfere with the development of CC by reducing the high-risk human papillomavirus (hr-HPV)-induced lesions that remain a major public health burden in all developing countries where organized screening programs do not exist. Globally, 85 % of all incident CC and 50 % of CC deaths occur in the developing countries. Unfortunately, most regions of Brazil still demonstrate high mortality rates, ranking CC as the second most common cancer among Brazilian women. Recently, CC screening programs have been tailored in the country to enable early detection of CC precursor lesions and thereby reduce cancer mortality. A combination of HPV testing with liquid-based cytology (LBC) seems to be a promising new approach in CC screening, with high expectation to offer an adequate control of CC burden in this country. Human papillomavirus (HPV) is a non-enveloped small (8000 bp) DNA-virus with circular double-stranded DNA, showing a specific tropism for human epithelial cells both in the skin and mucous membranes , 2. SincHPV is the causal agent, necessary for the development of CC, and identified in practically all cases when highly sensitive detection methods are used. Cancer development is associated with HPV persistence that leads to cellular transformation, disease progression to precancerous lesions and, if uninterrupted, to an invasive cancer , 8.HPV types infecting genital mucosa (in both genders) are subdivided into high-risk (hr) and low-risk (lr) groups. This classification is based on established epidemiological evidence on their association with benign, precancerous and cancer lesions. The hr-HPV are 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59; whereas the lr HPVs include 6, 11, 40, 42, 43, 44, 54, 61, 70, 72 and 81. It is now obvious that both hr- and lr-HPV infections do occur in different anatomic sites, inducing either benign, premalignant or malignant lesions [The HPV life cycle is intimately linked with the programmed differentiation process of stratified squamous epithelia , starting from the undifferentiated cells of the basal layer, capable of continuously dividing, and progressing through highly specific cellular events towards fully matured keratinocytes . In principle, HPV life cycle has three major phases. First, infectious virions access the basal layer through a micro-lesion, forming a virus reservoir where the viral genome is conserved as a low–copy number episomal form within the infected cell. Second, the viral genome replication occurs, whereby host cell DNA and the infected cells are divided into daughter cells, which can persist in the basal and parabasal layers and proceed to the division, or move and initiate the differentiation process. In the latter, activation of the late (L) gene expression and vegetative viral DNA amplification begin. This amplification leads to synthesis of a huge number of viral copies , 10, 11.cervical transformation zone (TZ), where squamous epithelium meets the glandular epithelium of the endocervical canal. HPV-induced cell transformation is mediated by the viral E6 and E7 oncoproteins interfering with the cell cycle regulators of the host cells, starting at the basal cells layer and gradually extending to the full epithelial thickness [HPV infection is most easily transmitted in sexual intercourse, and the risk is higher in women with an early onset of sexual activity (due to higher exposure to the virus) as well as in those with impaired immunity –16. Cervhickness , 18. Onchickness , 20.The great majority of sexually active women and men are likely to be infected by HPV at least once in their life-time . In geneAround 70 % of all CC cases are associated with hr-HPV 16 and 18, in contrast to benign genital warts, which are predominantly related to HPV 6 and 11. Of all hr-HPV genotypes, HPV 16 shows the highest probability for persistence, and thus has a major impact on the cancer risk. HPV 18 is the most frequent genotype found in adenocarcinomas , 6. Up tAccording to the estimates for 2012, more than 528,000 incident cases and 266,000 deaths due to CC were detected worldwide –27.Fig. The screening strategy in Brazil is targeted to women aged between 25 and 64 years, repeated every 3 years. Accordingly, the women should have Pap smear taken each three years if she has two consecutive normal smears in the previous screening rounds . In the It is established that an organized population-based screening and treatment of the detected precursor lesions can decrease the disease mortality by 80 %, as shown e.g. in Finland , 21. CC The first national initiative by the Brazilian government to implement a national screening program for CC was taken 40 years ago . Since tSince its introduction, the cytological Papanicolaou smear (Pap test) has been considerate as the method-of-choice in organized screening for CC. When implemented as an organized program at population level, Pap smear screening has resulted in a substantial decrease of both incidence and mortality of CC , 21, 31.Brazil has not implemented an organized population-based CC screening program, and not even a universal system to invite all women to realize these examinations. However, the government has designed a program to identify and control the cytopathology examinations performed. The first examination used to identify CC precursor lesions is the Pap test, targeted to women from 25 years  to 64 years, repeated every 3 years for women who had two consecutive negative smears within five years. However, the guidelines  do not recommend screening for women younger than 25 years by Pap test, mainly because most of these lesions clear spontaneously , 33.Recognition that HPV infection is the necessary cause of CC opened new possibilities for prevention strategies, including the primary prevention with highly effective prophylactic HPV vaccines, and the secondary prevention using highly sensitivity HPV tests, which has significantly improved the performance of the screening programs based on the Pap test –35.Molecular techniques have been considered better than cytology regarding the sensitivity and reproducibility in detecting CIN 2 or CIN 3. Proper treatment of the precursor lesions detected by screening should prevent the development of invasive CC and reduce the incidence and mortality. Some HPV tests used in screening have achieved a 60–70 % reduction in invasive CC incidence as compared with cytology alone . DespiteDuring the past several years, a plethora of novel methods have been developed for the hr-HPV DNA testing in CC screening. The use of HPV DNA testing for oncogenic types has been proposed as a co-test with cytology for screening women above 30 years of age, showing higher accuracy as conventional Pap smear screening , 39–41. The overall acceptance of HPV testing is higher among women who have experience on self-sampling (made at home), as compared with the physician collection . MoreoveFor almost 60 years now, cervical cytology , has been the gold standard in CC screening programs. Based on early detection of CC precursor (CIN) lesions, both tests represent measures of secondary prevention of CC. However, organized screening based on cervical cytology has severe limitations in implementation; extensive training is mandatory, good laboratory infrastructure is necessary, and standardization and quality control are essential , 42, 46.The well-established natural history of HPV infections is the sound basis for the rational use of CC preventive measures based on HPV testing. The single most important goal of CC screening is to reduce mortality. This is achieved by decreasing the incidence of invasive disease by detecting the precancerous lesions, followed by their adequate treatment , 46, 47.Although HPV vaccination of teenagers and young women has proven effective in many countries, the public health strategies to demonstrate effective prevention of CC still represent major obstacles to overcome. The cost-effectiveness analysis for all strategies to reduce CC incidence should involve both the screening and HPV vaccination in an integrated and organized manner. At the moment, the preferable option in Brazil seems to be the use of HPV testing for primary screening, followed by triage of all HPV+ cases with the Pap test. A recent Mexican trial  showed aAccording to WHO, HPV types 16 and 18 are responsible for 70 % of all CC cases worldwide. The currently available vaccines against these two HPV types have the potential of reducing the incidence of cervical and anogenital cancer. Brazil has a population of >64 million women aged above 15 years and at risk to develop CIN and CC, who certainly would benefit from HPV vaccines . In thisWith the widespread implementation of HPV vaccines, HPV infections and HPV-related lesions will decrease substantially, which might increase the rates of false-negative results in cytology, in addition to reduced specificity. The combination of HPV vaccination with HPV testing and cytological triage is suggested to be the optimal algorithm to protect women against CC , 34, 47.The most important applications of HPV testing include i) organized screening programs to optimize an early detection of HPV-induced CC precursor lesions, and, ii) to conduct adequate follow-up of the women who have been treated for high-grade CIN.Some novel technical innovations of HPV testing are particularly designed for remote areas, without compromising the test performance for hr-HPV detection. Certainly self-sampling for HPV testing still needs standardization to make it compatible with the usual sampling techniques. Once successfully accomplished, it has a potential to become a valuable screening tool for large underprivileged populations, thus contributing to alleviating the significant disease burden in these countries.


Characteristics associated with mental disorders in regression analyses included displacement (particularly longer-term), cumulative trauma exposure, female gender, older age, poor community conditions, and bad household economic situation; coefficients ranged from 1.50 to 3.79. PTSD, depression, anxiety, and comorbidity were associated with increases in disability of 6.4%, 9.7%, 6.3%, and 15.9%, respectively. A high burden of psychiatric symptoms and disability persist among conflict-affected persons in Georgia.There remains limited evidence on comorbidity of mental disorders among conflict-affected civilians, particularly internally displaced persons (IDPs) and former IDPs who have returned to their home areas (returnees). The study aim was to compare patterns of mental disorders and their influence on disability between IDPs and returnees in the Republic of Georgia. A cross-sectional household survey was conducted with adult IDPs from the conflicts in the 1990s, the 2008 conflict, and returnees. Posttraumatic stress disorder (PTSD), depression, anxiety, and disability were measured using cut scores on Trauma Screening Questionnaire, Patient Health Questionnaire 9, Generalised Anxiety Disorder 7, and the WHO Disability Assessment Schedule 2.0. Among the 3,025 respondents, the probable prevalence of PTSD, depression, anxiety, and comorbidity (>1 condition) was 23.3%, 14.0%, 10.4%, 12.4%, respectively. Pearson correlation coefficients ( It is well recognised that populations affected by armed conflict are frequently exposed to traumatic events and daily stressors and at risk of elevated levels of mental health disorders  IDPs and did not examine levels of comorbidity or adjusted risk factors  the presumed prevalence of the mental disorders of PTSD, depression, anxiety, and their comorbidity; (b) the influence of displacement status, time, trauma exposure, and demographic and socioeconomic characteristics on mental disorders; and (c) the influence of the mental disorders and their comorbidity on disability and how this varied by displacement status.The study used a cross-sectional survey design and multistage random sampling, with stratification by region and displacement status. A total sample size of 3,600 men and women aged ≥18 years was determined to meet the statistical requirements of the overall study. This consisted of 1,200 respondents from each of the three main conflict-affected populations in Georgia: those displaced as a result of conflicts in the 1990s (1990s IDPs), those displaced after the 2008 conflict (2008 IDPs), and former 2008 IDPs who have returned to their home areas after being displaced due to the 2008 conflict (returnees).n = 360; 120 per population group) were selected based on probability proportion to size method using a sampling frame of formal and informal IDP settlement population sizes throughout Georgia provided by the Ministry of Internally Displaced Persons, and lists of villages in the border region with South Ossetia provided by the governor's office in the Shida Kartli region. Within each primary sampling unit, the random walk method was used to randomly select households. Within the selected household one person was selected to be interviewed (based on nearest birthday). If there was no response at the household after three visits (on different days and at different times), the next household on the route was visited, with the same process used for refusals or interrupted interviews to ensure the desired sample size. For the purposes of this study, the overall sample  was restricted to only 1990s IDPs or 2008 IDPs or 2008 returnees, with respondents who had been displaced from both the 1990s and 2008 conflicts excluded (n = 256) as well as those who reported that they had never been displaced (n = 319). The final sample size was therefore 3,025 with a response rate of 84.0%. The sample respondent characteristics, by displacement status, are shown in TablePrimary sampling units , which consists of 10 items on PTSD symptoms over the past 1 week, with 0 = In this study, the TSQ, PHQ-9, GAD-7, and WHODAS 2.0 showed good internal reliability, with Cronbach's α scores of .86, .86, .90, and .91, respectively. We also conducted a separate pilot survey of 110 randomly selected IDPs living in Tbilisi to assess the instruments’ test-retest reliability by administering the TSQ, PHQ-9, GAD-7, and WHODAS 2.0 to the same respondents 4 days apart, and the intraclass correlation results for them were .97, .98, .96, and .98, respectively , employment status, household assets, and household economic situation .The main survey questionnaire also contained items on exposure to a range of violent and traumatic events adapted from the Harvard Trauma Questionnaire, which was designed to measure experiences of violent and traumatic events among civilian populations in a range of cultural settings , comorbidity of more than one condition, having all three conditions, and having a single condition with no comorbidity. Pearson's correlation coefficients among the three conditions were also calculated.p < .05). The same variables were then used in separate models for PTSD, depression, anxiety, and comorbidity to examine any differences between the disorders. In this regression analysis, the data were weighted to reflect actual proportions of 1990s IDPs, 2008 IDPs, and returnees in the overall conflict-affected population of Georgia, based upon the sampling frames noted above.Multivariate logistic regression analysis was then used to examine the association of displacement status and time, trauma exposure, and demographic and socioeconomic characteristics with outcomes of PTSD, depression and anxiety, any condition  and comorbidity . Exploratory bivariate analysis was initially conducted with the outcome of any condition and a stepwise approach used to select variables in the final model, which remained statistically significant  with the presumed mental disorders and with comorbidity is shown in p < .001) correlations between the three scores, with a Pearson correlation coefficient of .40 for PTSD with depression, .38 for PTSD with anxiety, and .52 for depression with anxiety. At between .30 and .60, these can be considered moderate levels of correlation  for the 1990s IDPs compared with the 2008 IDPs and returnees for PTSD , depression , and anxiety . The only significant difference between the mean scores for 2008 IDPs and returnees was for PTSD (p < .001).There were significantly higher mean scores  for PTSD with depression, PTSD with anxiety, and depression with anxiety were slightly higher among the 1990s IDPs  than the 2008 IDPs  and returnees . The characteristics associated with the three disorders and then their comorbidity are shown in TablesOR] = 0.63), and around two thirds for depression (OR = 0.33), and around half for any one of the three (OR = 0.52). The 2008 IDPs were also associated with a significantly lower probability of depression (OR = 0.54) and having ≥1 condition (OR = 0.67) than 1990s IDPs. The same models were also run comparing returnees with a reference category of 2008 IDPs ; these also showed a significantly lower probability among returnees compared to 2008 IDPs for PTSD (OR = 0.67), depression (OR = 0.61), anxiety (OR = 0.64), any condition (OR = 0.60), and ≥ one condition above the cut score (OR = 0.67).The Pearson correlation coefficients (p < .05) between the three population groups in exposure to traumatic events , older age, and bad/very bad household economic situation and community conditions Tables and 4. TThis study provides the first representative data on mental health of adult IDP populations in Georgia. We recorded levels of presumed PTSD, depression, and anxiety of 23.3%, 14.0%, and 10.4%, respectively, for the combined study sample. These are lower than the rates of depression (70%) and anxiety (73%) recorded in a previous study of elderly IDPs in Georgia . Mental disorders may also become entrenched over a sustained period of time when also coupled with lack of access to adequate care and treatment as appears common in Georgia . The lack of available data on the prevalence of mental disorders among the general population of Georgia also prevents comparisons with them. The study did not include IDPs hosted by relatives or friends or living independently away from the formal and informal settlements. The long recall period could increase potential recall bias for exposure to violent and traumatic events, particularly for the 1990s IDPs. The study did not assess respondents’ psychiatric history and functioning levels prior to their exposure to the conflicts and forced displacement, largely due to concerns over recall bias (Simon & VonKorff, In conclusion, this study highlights the persistence of PTSD among conflict-affected persons in Georgia and the need for a comprehensive approach to tackling trauma-related and common mental disorders and functioning.


Babesia caballi, Theileria equi, Neospora caninum and Chlamydia abortus was determined using commercial assays, and risk factors associated with seropositivity to the different infectious agents was established. The most seroprevalent agent detected was EHV-4 (96.7%), followed by WNV (44.2%), and IAV (41.8%). Horses >3 years, used for work or sports, and with access to pastures, had significantly increased probability to be seropositive to WNV, whereas horses used for breeding and recreational purposes, being stabled, and without access to pastures, had significantly greater probability to be seropositive to IAV. Seroprevalence to B. caballi (19.9%) was lower than to T. equi (38.1%). For B. caballi, access to pastures was determined as a risk factor, whereas being older than 3 years was established as a risk factor for T. equi. Low seroprevalences were determined for EHV-1 (5.0%), EVAV (5.0%), C. abortus (4.8%), and N. caninum (4.4%). Mares having history of abortion were more likely to be seropositive to EHV-1, whereas horses >3 years, used for work and sports, and mares having multiple parturitions, were more likely to be seropositive to N. caninum. None of the horses were seropositive to EIAV. Earlier, only diseases caused by EIAV, WNV and piroplasmosis were reported in Costa Rica. The present study however, determined the presence of carriers for EHV-1, EHV-4, and EIAV.Blood samples from 181 equines from the Central Valley of Costa Rica were collected in the year 2012 to determine the presence of antibodies against selected infectious agents in horses and to determine the risk factors associated with these agents. The presence of antibodies against Equine Infectious Anemia Virus (EIAV), Equine Herpes Virus 1 and 4 (EHV-1 and EHV-4), West Nile Virus (WNV), Influenza A Virus (IAV), Equine Viral Arteritis Virus (EVAV),  Babesia caballi, Theileria equi, Neospora caninum and Chlamydia abortus are known to cause clinically important diseases in horses .Infections due to Equine Infectious Anemia Virus (EIAV), Equine Herpes Virus 1 and 4 (EHV-1 and EHV-4), West Nile Virus (WNV), Influenza A Virus (IAV), Equine Viral Arteritis Virus (EVAV), et al., 1999; Reed and Toribio, 2004).EIAV is a retrovirus that causes a disease characterized by recurrent febrile episodes, anemia, rapid loss of weight and edema. All infected horses, including those that are asymptomatic, become carriers and are infectious for the rest of their life . Equine herpesvirus infections in horses remain a significant cause of abortion, respiratory and neurologic disease. EHV-4 is considered to cause respiratory tract disease, known as rhinopneumonitis among horses worldwide, whereas EHV-1 seems responsible especially for abortions, neurologic and respiratory disease . WNV is a member of the Japanese encephalitis serogroup within the family Flaviviridae and was introduced in 1999 to the American continent. This arbovirus is typically transmitted by et al., 2011).Horses are exposed to numerous mosquito bites and may serve as sensitive sentinels for local arbovirus activity, which can be detected by screening for the novel production of specific virus-reactive antibodies. Horses infected with WNV may develop neurologic disease, sometimes leading to death, but most infections are subclinical and will only be detected through testing for seroconversion .et al., 1996).EVAV causes sporadic cases of respiratory disease and abortion, mares and geldings discharge the virus after acute infection, however 30% to 60% of stallions become persistently infected. In these animals, EVAV is maintained within the reproductive tract, and is shed continuously in the semen. Persistent infection with EVAV in stallions has no negative consequences for fertility, but mares inseminated with virus-contaminated semen can develop an acute infection. These mares then shed large amounts of virus in respiratory secretions and urine, leading to spread of the virus to other susceptible horses. Acute infection at later stages of gestation can lead to abortion .Equine piroplasmosis is caused by N. caninum is a protozoan parasite, which affects dogs as definitive hosts, and several mammalian species as intermediate hosts, mainly causing abortions and central nervous system disorders. Horses can serve as an intermediate host. Tachyzoites of N. caninum were first found in a fetus lung, whereas tachyzoites of Neospora hughesi were isolated from an adult horse . In horses, neosporosis causes abortions, and neonatal, visceral and neurological disorders. N. caninum is related to abortions whereas N. hughesi to neurological disease . Recently, Dangoudoubiyam et al. (2011) detected anti-Neospora spp. antibodies in 3.5% horses from Costa Rica by using an NhSAG1 ELISA.C. abortus, formerly Chlamydophila psittaci serotype 1, has been rarely detected in horses with acute respiratory infections until now , where it was found in the lungs of both, clinically healthy horses and those with recurrent airway obstruction. Using molecular techniques, C. abortus was recently detected in a case of abortion .et al., 2011; Hobson-Peters et al., 2011; Vega, 2011; Posada, 2012; Fonseca-Salazar, 2013). The purpose of the present study was to determine the presence of antibodies to selected infectious agents in equines from provinces of the Central Valley from Costa Rica and to determine risk factors associated with these agents.Epidemiological studies have been conducted in advanced countries, but there are only few reports of the prevalence of these agents in tropical countries  and in Costa Rica . The formula described by Wayne (2002), using an expected prevalence of 50% (confidence level of 95% and error of 5%) was used. Selection of the animals for sampling was based on voluntary participation of the owners of the horses; inclusion criterion was that the animals had never been vaccinated against the infectious agents in study.A cross-sectional survey of 181 equines living in the Central Valley of Costa Rica was carried out, to determine presence of antibodies against several infectious agents  was taken from the jugular vein of each equine and maintained at 4°C until arrival to the laboratory, serum was then separated and stored at -20°C until analysis. In addition, a questionnaire was used to collect general data, such as provenance (province), gender, age (less than 3 years and more than 3 years) and breed. Also, activity for which the horse was used , and information about place of living and access to pastures was collected. Finally, the clinical history was inquired, giving special emphasis to respiratory  and reproductive (abortions) diseases of the horses in the past.B. caballi, T. equi and N. caninum, and 146 were tested for antibodies to IAV and C. abortus, since the serum samples of some animals were not sufficient to perform all serological tests.All 181 sera were examined for the presence of antibodies to EIAV, EHV-1, EHV-4, WNV, EVAV, ® EIAV ID ; SVANOVIR® EHV-1/EHV-4 indirect ELISA; ID Screen® West Nile competition ELISA; ID Screen® Influenza A competition ELISA; ID Screen® Equine Viral Arteritis indirect ELISA; VMRD®B. caballi competition ELISA (sensitivity and specificity 100%); VMRD®B. equi competition ELISA ; VMRD®N. caninum competition ELISA ; and ID Screen®C. abortus competition ELISA .Serum samples were tested with commercial immunodiffusion (ID) or immunoenzymatic (ELISA) assays following the manufacturers´ instructions. The following assays were used: VMRDActivity and for which the horses were used, were combined in two groups for statistical analysis. The first group comprised of horses used for recreational and breeding purposes, and the second group comprised of horses used for work and sports. Animals in the first group were moved more often to other areas (provinces) of the country, either through fairs or street exhibitions (“topes”), whereas animals in the second group remained mainly in the same area. Sporting events took place only in the province of San Jose.Descriptive statistic about general characteristics of the horses and diseases comprised of frequencies, measures of central tendency  and dispersion (standard deviation).To assess the relationships of independent variables with the diseases, the odds ratio (OR) rate ratio was calculated using unconditional logistic regression. The regression procedure consisted of two steps:P <0.25 in the univariable analysis were included. A backward building model was followed based on the likelihood ratio test.1) univariable analysis, and 2) multivariable analysis. In the second step, all variables with The process of exclusion-inclusion of each variable into the multivariable model tested confounding and interaction by comparison of the estimated coefficients in the new model with the estimated coefficients and likelihood ratio of the old model. Confounding was deemed present if at least one coefficient changed more than 10%  or if at least one coefficient changed more than 25% .Finally, variables that were excluded in the univariable step were checked on collinearity with the variables in the final model to check for potential confounding by calculation of simple correlations. The data was analyzed using EGRET 2.0 (Cytel Sotware Corp.)The 181 equines samples were collected in the provinces of Alajuela (76), Cartago (5), Heredia (28) and San José (72). From the total, 98 (54.1%) were males (36 castrated), 83 (45.9%) were females, and 116 (64.1%) animals were older than 3 years old . The main breed was represented by Costarricense de Paso , followed by Iberoamericanos  and Andalusian , whereas 40 animals (22.1%) belonged to other breeds .Most of the animals  were used for recreational  and breeding purposes , and 56 (30.9%) for work  or sports . A total of 162 (89.5%) horses lived in stables (average of horses in stables: 50), the remaining animals lived on paddocks 19 (10.5%), and only 35 (19.3%) had access to paddocks, however all lived with other equines. The owners revealed respiratory disease  in 14 (7.7%) animals, whereas 167 (92.3%) never noticed any respiratory symptom.A total of 44.0% (22/50) of females in reproductive age had given birth, and only 8.0% (4/50) had suffered abortions. The results of the serological analysis of the horses to the different infectious agents are shown in T. equi (38.1%). The risk factors determined for the different infectious agents are shown in Almost all animals (96.7%) were seropostive to EHV-4, the most prevalent infectious agent among horses, followed by WNV (44.2%), IAV (41.8%), and None of the horses in the present study tested positive for EIAV, consequently no risk factors could be determined. Presumably, most of the animals that participated in this study were previously tested for EIAV , since they need negative results to be housed in the stables or to participate in competitions.However, EIAV occurs in Costa Rica and has a wide distribution, as reported by Pineda (1998), who found that 29.5% of participating horses in the Rally of Tilarán were persistently infected and were inapparent carriers of EIAV.et al., 2013). The eight EHV-4 seropositive horses with reported respiratory disease were also seropositive to IAV, which would indicate that it is most likely to be the agent responsible for the clinical presentation and not EHV-4.Antibodies to EHV-4 were detected in 96.7% of the animals tested, showing a wide distribution among horse population. No risk factors could be established, due that most of the animals were seropositive, however most  of the owners of seropositive animals did not notice respiratory disease in their animals which leads us to conclude that the infection may occur subclinically in Costa Rica . The EHV-1 seropositive animals were three stallions and six mares, living in the Alajuela (5), San José (3) and Heredia (1) provinces. They were used for recreational  and breeding purposes , maintained with other horses, and had access to shared pastures, representing a source of infection for other horses .On the other hand, only nine (5.0%) animals yielded positive results to EHV-1, a positive correlation between seropositive mares and abortion was determined (p=0.027), which is in agreement with the literature, that reported EHV-1 as the most common equine herpesvirus associated with abortions .To our knowledge, this represents the first report of the presence of EHV-1 and EHV-4 in Costa Rica, finding a wide distribution for EHV-4, and limited distribution of EHV-1, which is in accordance with reports from Ataseven A total of 80 (44.2%) equines showed antibodies to WNV, they were distributed in all provinces . Animals >3 years old, mainly used for work and sports, and that had access to pastures had more probability to be seropositive, than younger and stabled horses; results that are in accordance with the epidemiology of the virus .et al. (2011), who detected in 2004 antibodies in 28% of equines in the Guanacaste province. In 2009, SENASA  reported the first equine case in this province. Our results indicate, that WNV infection occurs silently in equines living in the provinces of the Central Valley of Costa Rica. Possible explanations for reduced disease burden in our horses may be due to the presence of a less virulent WNV strain in Latin America and the Caribbean or due to serological cross-reaction with other related flaviviruses present in the region .The first evidence of WNV activity in Costa Rica was reported by Hobson-Peters et al., 1999).With respect to Influenza A virus, a total of 41.8% (61/146) equines showed antibodies to IAV, the seropositive animals were distributed in Alajuela (28), San José (24), and Heredia (9). Equines >3 years, used for breeding and recreational purposes, mainly stabled, although with access to pastures were determined with more probability to be seropositive to IAV. These findings are in agreement with the epidemiology of the disease that needs close contact between horses to be transmitted (stabulation), and due, that animals used for breeding and recreational purposes, more often participate in fairs and street exhibitions in Costa Rica, having more close contact to other horses .A similar result as EHV-1 was obtained for EVAV, a total of 9 out of 181 (5.0%) equines were seropositive; however no risk factors were determined, due to the small amount of positives. The EVAV seropositive animals were eight males (two of them not castrated) and one mare, most animals (8/9) were older than 3 years, and living in the provinces of Alajuela (3), San José (3), Heredia (1), and Cartago (2). All the horses were used for recreational purposes, and were stabled with other horses. Since most infections of EVAV occur subclinical or asymptomatic, laboratory tests are very important. The detection of two seropositive stallions suggests a risk of dissemination of the virus throughout the country, if control measures are not implemented (Murphy T. equi (38.1%) than to B. caballi (19.9%) was determined, which is in agreement with reports from Posada (2012) and Sellon and Long (2007). This could be due, to the fact that horses infected with T. equi remain seropositive and as reservoirs of the parasite for life, whereas horses infected with B. caballi are only seropositive for several years . However, horses >3 years and with access to pastures were more likely to be seropositive to T. equi and B. caballi, respectively, which is in accordance with the fact that equine piroplasmosis is endemic in Costa Rica, due to the presence of tick vectors .A higher seropositivity to A total of 45.8% (83/181) animals were positive to at least one type of piroplasma, and the distribution was as follows: Alajuela (36), San José (27), Heredia (16), and Cartago (4); and 12.1% (22/181) horses showed antibodies against both agents. Outbreaks of clinical disease are uncommon in endemic areas; acute clinical disease is most often observed when naive horses are moved into endemic areas .N. caninum, six males (four of them castrated) and two mares, all living in the San José province. Animals >3 years old, used for work or sports had more probabilities to be seropositive to N. caninum, also mares with at least one delivery. Further studies are required to determine whether these animals were infected with N. caninum or N. hughesi . Using molecular techniques, N. caninum was recently detected in cases of abortion and neonate mortality ; also, seroprevalences of N. caninum had been reported previously in the United States of America .A total of eight (4.4%) equines showed antibodies to C. abortus, a relatively low seroprevalence. No risk factors were established due to the small size of the positive animals. The C. abortus seropositive animals were six males, two of them castrated, and one mare. All horses were >3 years old and living in the Alajuela (2), San José (3), and Heredia (2) provinces. Two males were used for breeding, three for recreational, and one for work purposes. The mare was used for sports. The animals were held stabled with other horses, and only three had access to shared pastures. This is the first report of C. abortus seropositivity in horses from Costa Rica, involvement of this agent in abortions need further investigation in future studies.Finally, seven out of 146 (4.8%) horses were found to be seropositive to N. caninum. Actually, only diseases caused by EIAV, WNV and Piroplasmosis were reported to be present in Costa Rica.Almost all studied agents in the present study are notifiable to the International Organization of Epizooties, with exception of EHV-4 and C. abortus in horses of the Central Valley of Costa Rica were determined, also, that WNV seems to be disseminated among the horse population silently. Veterinarians are recommended to take into account these infectious agents in the diagnosis and differential diagnosis of respiratory and reproductive diseases in horses.However, presence of possible carriers of EHV-1, EHV-4, EVAV, and The Authors declare that there is no conflict of interest.


Multiple linear regression analysis was used to assess an association between workplace and lung function. Lung function assessed on the basis of calculation of longitudinal FEV1 (FVC) decline was similar in all studied groups. However, multiple linear regression model used in cross-sectional analysis revealed an association between workplace and lung function. In the group of welders, FEF75 was lower in comparison to operators and other miners as early as after 10 years of work. Simultaneously, in smoking welders, the FEV1/FVC ratio was lower than in nonsmokers . The interactions between type of workplace and smoking  in their effect on FVC, FEV1, PEF, and FEF50 were shown. Among underground working copper miners, the group of smoking welders is especially threatened by impairment of lung ventilatory function.The aim of the analysis was to retrospectively assess changes in lung function in copper miners depending on the type of workplace. In the groups of 225 operators, 188 welders, and 475 representatives of other jobs, spirometry was performed at the start of employment and subsequently after 10, 20, and 25 years of work. Spirometry Longitudinal Data Analysis software was used to estimate changes in group means for FEV Copper miners working underground are exposed to mine gases containing, among other things, nitric oxides. Endogenous nitric oxide (NO) plays key roles in lung biology, being involved in pulmonary neurotransmission, as well as host defense, airway and vascular smooth muscle relaxation, mucociliary clearance, airway mucus secretion, inflammation, and cytotoxicity , 2. Simu2) and nitric oxide, dissolving in water contained in the bronchial mucus, form nitric acid and nitrous acid. These acids may produce acute pulmonary injury due to inhalation of vapors and gases originating from nitric acid solutions. Acute poisoning may occur as a result of short-term exposure to nitric oxides at high concentrations (94–7500 mg/m3) in the course of mining disasters, breakdowns, and accidents. Nitric oxides in very high concentrations can cause immediate death, toxic pulmonary edema occurring within 48 hours, pneumonia [On the other hand, the respiratory system is known to be critical for toxicity of exogenous nitric oxides. Nitric dioxide , that is, below Maximum Allowable Concentration (MAC). The short-term exposure limit for nitric dioxide  was sometimes exceeded and in some measurements in 2007 reached as much as 3,96 mg/m3.Results of spirometric tests, which have been conducted in 888 miners during their 25 years of employment at the same copper mine, between 1980 and 2005, in Poland, in Lower Silesia, were analyzed. Miners were working underground as operators (225 men), welders (188 men), and other workers (475 men): mechanics, electricians, transport workers, and hewers . The samples of mine air were taken every month to determine time weighted average (TWA) and a short-term exposure limit (STEL) for nitric oxides. The determined TWA concentrations ranged from subdetectable (most often) to 2,02 mg/m2).Anthropometric data (body weight and height) were collected in local health centre, using calibrated equipment and standardized methodology. Body mass index (BMI) was estimated as the ratio of weight to height squared (kg/mSpirometry was performed on workers four times: at the start of employment (between 1980 and 1983) and then 10 years after (between 1989 and 1991), 20 years after (between 1998 and 2000), and 25 years after the beginning of work (between 2003 and 2005). The procedures were in accordance with ethical standards and the Helsinki Declaration of 1975, as revised in 1983.At the time of the first spirometry, among the miners, 435 men were nonsmokers and 354 were smokers , and in 99 cases there was no information on smoking. A respiratory disease was diagnosed in 15 workers: pneumoconiosis (in eight miners) or allergic respiratory disease (in seven workers). There were no data on respiratory diseases in 108 men. In some groups of workers, results of blood count were analyzed. The number of miners, including smokers and men with respiratory disease, has changed over the period of employment, as shown in 1), forced vital capacity (FVC), peak expiratory flow (PEF), and four parameters of forced expiratory flow (FEF): FEF25, FEF50, FEF75, and FEF25–75. The mean FEV1/FVC ratio  was calculated. The technical accuracy of performed spirometry tests and the precision of collected data were monitored by technicians trained in ATS standards. Inspection of flow-volume curves served to control complete exhalation, indicated by gradual flow drop to zero. Interpretation of the results was based on guidelines published in 2005 by the experts of the American Thoracic Society (ATS) and European Respiratory Society (ERS) concerning the correctness of the implementation and evaluation of spirometry [1, FVC, and FEV1/FVC, a lower limit for normal value (LLN) which corresponds to the fifth percentile in healthy nonsmokers and/or a lower limit for normal decline were estimated [1 and FVC in relation to mean predicted values based on group demographics . For the first 8 years of follow-up, SPIROLA uses the limit of longitudinal decline (LLD) which takes into account expected within-person variation in FEV1 or FVC and the duration of follow-up. After 8 years of follow-up, the age at which the individual is projected to develop lung function impairment is considered in the evaluation. Using SPIROLA program, we also evaluated whether FEV1 and FVC slopes for studied cohort exceeded 40 mL per year  and, on the basis of risk list function, determined how many subjects met criteria for abnormality.Spirometry was carried out at first according to American Thoracic Society criteria (as described in ) and theirometry . In casestimated . NIOSH  was also applied with one- or multidimensional significance tests. Correlations between variables were checked using Spearman coefficient. p value less than 0,05 was accepted as statistically significant. Analyses were carried out using STATISTICA version 12.0.Spirometric indices were presented as mean ± SD, median and IQR, and percentile: 5% and 95%. Depending on the type of variable distribution, parametric or nonparametric methods of analysis were used. In the case of normal distribution, 2 in all groups. At this time, BMI was greater than 30.0 kg/m2 in 113 miners and greater than 35.0 kg/m2 in 13 men. BMI in welders was higher than in remaining miners. Changes in body mass index during 25 years of work were similar in all groups of workers, whereas the age differences were not similar . In the group of miners studied after 20 years of work, the inverse relationship between age and FVC  and between age and FEV1  was observed.The mean height of operators, welders, and other miners was similar. At the beginning of employment, the median BMI values were greater than 25.0 kg/m similar . Among s1/FVC ratio was greater than 70% , also FEV1 was less than LLN. With the expiration of the employment period, the number of miners with obstructive disorders decreased; after 10 years, it was 31 men, after 20 years 26 men, and after 25 years 30 men. The number of miners with both FEV1/FVC and FEV1 lower than LLN was 3, 4, and 7 after 10, 20, and 25 years of work, respectively.In spirometry tests performed at the start of the employment and after 10, 20, and 25 years, in each group , the mean FEVthan 70% . HoweverP-paired test for dependent variables performed in the whole group showed a gradual, significant decrease in FEV1/FVC ratio over a 25-year period of occupation  decreased in subsequent years to 3,825 ± 0,71 L. Using SPIROLA software, it was shown that the mean rate of FEV1 absolute decline from first to last measurement was 10.0 mL/year (relative decline was 0.3%/year), and mean slope for FEV1 (LLD) amounted to −12.4 mL/year (relative slope: −0.3%/year), with root mean square error (RMSE) of 117 mL. Simultaneously, in the course of performed work, a decrease in % PEF, % FEF25, and % FEF75 was shown  and/or FVC  was present in 28% of operators, 17% of welders, and 24% of other miners. Trends in FEV1 and FVC over time in each group of miners were presented in In group of copper miners employed as operators, during 25 years of follow-up, the mean group slope was −1,0 mL/year, with within-person variation for the group  of 329 mL, whereas mean slope for FVC was 10 mL/year, with RMSE of 127 mL. In the same period, in group of welders, mean group slope for FEV75  were lower in comparison to group of other workers   and FEF, resp.) . Simulta, resp.) .75, these parameters were lower in the group called “others,” in comparison to the group of operators or welders. Multiple linear regression analysis adjusted for age, height, weight, BMI, smoking, and presence of respiratory disease showed an association between workplace and lung function. The significant beta-coefficients for FVC, FEV1, FEF25–75, and FEF50 have been demonstrated  lower % PEF , in comparison to operators  and others . The mean FEF25 values in welders  and “others”  were lower than in operators , p < 0,05 and p < 0,01, respectively , in comparison to healthy workers .Among all confounding factors, height and absolute values of BMI had the highest positive beta-coefficients in a linear regression model , whereas presence of respiratory disease had the lowest negative coefficients. The analysis of spirometric parameters depending on the coexisting respiratory disease showed that % FVC in the subgroup of 15 miners diagnosed with respiratory disease was lower  lower in smokers than in nonsmokers . After 10 years of work, lower FEV1/FVC in smoking, in comparison to nonsmoking welders, was shown  FEV1/FVC ratio would fall slightly with age. Therefore, it was better to refer obtained results to LLN, which includes age, than to fixed values. FEV1/FVC reduced below LLN was shown in the first spirometry in about 7% of subjects: in about 5% of these miners, the mean FEV1 was greater than LLN, and thus mild obstruction could be diagnosed, whereas, in 1% of miners, FEV1/FVC index and FEV1% were lower than LLN, leading to a diagnosis of moderate bronchial obstruction. Among these subjects, there were smokers (nearly 45%) and men treated due to respiratory diseases. In relation to these data, the occurrence of bronchial obstruction in a few percent of miners appears to be only a small percentage of the total number of studied workers. However, it should be an indication to intense preventive activity, especially concerning smokers and miners diagnosed with respiratory disease.An obstructive ventilatory disorder is a disproportionate reduction of maximal air flow from the lung in relation to the maximal volume that can be displaced from the lung. In the first spirometric test performed in 888 workers, the most important indicator of bronchial obstruction, the FEVrt panel , 24, thaiagnosis –27. In 21/FVC index was about twice lower (3%) than in the first spirometry. After 20 years, bronchial obstruction could be diagnosed in 4,3% of miners and after 25 years in about 4%. A decreased number of men with low lung function during 25 years of observation, associated with small number of miners diagnosed with a respiratory disease, could be a consequence of the decreased percentage of smokers in the studied population. On the other hand, miners with a decreased FEV1/FVC index displayed gradual decrease in % FEF25 and % FEF75, which indicates the impairment not only of central, but also of peripheral bronchial function. It is documented that obstructive changes may be manifested as a reduction of air flow in the final phase of exhalation, which results in the maximum expiratory flow disturbances, especially at FEF25–75, FEF50, and FEF75. These changes are nonspecific, and the variance of these indicators in a healthy population is very large; hence, the reduction does not constitute a basis for diagnosis of pathology in case other results are correct [1/FVC ratio  was shown in our study, similarly as in others [After 10 years of employment, the number of miners with a reduced FEV correct . Many so correct . Moreoven others .Additionally, in comparison to the first spirometry, spirometric tests conducted after 25 years of the employment showed a significant decrease in the relative peak expiratory flow. The reduction of PEF is a characteristic form of bronchial obstruction in the course of chronic bronchitis or asthma , whereas1/FVC ratio, so the occurrence of restrictive changes in this group could be suspected. However, taking into account the simultaneous reduction in FEV1 , the number of people with suspected restrictive changes decreased to 9 (1.0%). After 10 years of work, the percentage of such workers was 0.6%, after 20 years, 1.2%, and after 25 years, 2.9%. Regarding the entire pool of workers, the problem of restrictive changes seems to be important only individually.In the absence of the measurement of total lung capacity, it is acceptable to classify the degree of restriction on the basis of the FVC; however, it is not synonymous with a diagnosis of restriction. Correct FVC values do not exclude the possibility of functional disorders concerning mechanical properties or diffusion across the alveolar-capillary barrier , 24. Our1/FVC ratio and FEV1 was observed in all groups of copper miners. Absolute and relative decline in FEV1 from first to last measurement were similar in operators, welders, and other miners and were much less than 40 mL/year . Nonetheless, the mean group slope for decline of FEV1 in welders (−21 mL/year) was greater in comparison to operators (−1 mL/year) or other workers (−8 mL/year). The rate of decline < 30 mL/year, established over 5 or more years, is not associated with increased morbidity and mortality regardless of the level of lung function [1 were similar in all studied groups of miners and amounted to less than 15% in long-term observation. The American College of Occupational and Environmental Medicine [1 and FVC, showing prognosis for subsequent years, were also similar in groups of operators, welders, and other miners. Thus, respiratory function assessed on the basis of the mean slope and within-person variation for FEV1 (FVC) in studied groups was similar in miners working underground at various workplaces. Impaired lung function, assessed on the basis of excessive FEV1 (FVC) decline, occurred in such a small number of miners that it was difficult to state whether there was increased predisposition of miners employed at any particular workplace.During 25 years of observation, the decrease in FEVfunction . Also, tMedicine  recommen75 than operators or other employees. These results can announce obstructive disturbances rather than restrictive ones. Also, Fidan et al. observed a decrease in parameters of forced expiratory flow, including FEF75, and, simultaneously, a higher risk for chronic bronchitis in welders in comparison to a control group [1. Also, other authors indicated a reduction in FEV1 or PEF in welders exposed to welding gases for more than 9 years, whereas workers with exposure of less than 5 years did not show any significant changes [1 over 11 years was related to occupational exposure and to smoking [Simultaneously, using the multiple linear regression model in cross-sectional analysis, the association between workplace type and lung function, independent of the impact of age, height, weight, BMI, smoking, and coexisting respiratory disease, was shown. This association appeared after 20 years of underground work. However, differences in spirometric indices between welders and other miners were apparent as early as after 10 years of work. At that time, welders displayed a slightly lower % PEF and a significantly lower % FEFol group . In caseol group . This co changes . Haluza  changes . Among B smoking .After 20 and 25 years of work, association between workplace type and lung function was shown as dependence of absolute spirometric parameters on type of job in a linear regression model. These parameters included indicators of not only obstruction, but also restriction. In comparison to welders or operators, other workers displayed lower lung function. These results can be a consequence of long-term exposure to mine gases containing nitric oxides as well as other gases toxic for the respiratory system, that is, hydrogen sulfide. The group of “other” workers included hewers who are the most exposed workers to dust and gases among miners.3 (rarely in 2001–2009), which is below respective Maximum Allowable Concentrations (MAC). The short-term exposure concentration (STEL) for nitric dioxide in some cases exceeded safe levels and in some measurements in 2007 reached 3,96 mg/m3. In 2002, MAC and STEL values were corrected according to the SCOEL recommendation  [In general, during the 25 years of this follow-up observation, the exposure of miners to nitrogen oxides, especially nitrogen dioxide, was low. The time weighted average (TWA) concentrations for nitric oxides ranged from subdetectable (most often) up to 2,02 mg/m5 mg/m3) .2. It may explain the positive correlation observed between BMI and FVC. Also, Chen et al. observed that, in subjects with normal weight, BMI was positively associated with FVC and FEV1 [In the analysis, the impact of confounding factors on lung function must not be omitted. In each group, the negative effect of age was typical , 29, whiand FEV1 .1 and % PEF, recognized as sensitive indicators of reduced air flow through constricted bronchi [1/FVC index in smokers was shown. The mean age of smoking workers was then 38,5 ± 3,61 years. Throughout the 25 years of the study, the biggest decline of lung function was observed in smoking welders  excessive variance in follow-up study was relatively high.One limitation of this analysis is the lack of a control or low to no exposure group for comparison. The disadvantage of the study may be a various number of miners in successive stages of observation. This has resulted in a reduced number of miners investigated in next stages of this evaluation, but especially between 1998 and 2000. It has been reported that results from longitudinal study of workers may be biased if there is a systematic exodus of certain types of workers between the surveys . Other s1, FVC, or FEV1/FVC ratio lowered below the LLN . Although this method is burdened with a 5% risk of false positive results, such a risk is generally acceptable. This type of presentation is regarded as the gold standard in epidemiological studies and recommended by scientific societies such as ATS, ERS, and BTS [In our analysis, the lung dysfunction was defined as FEV and BTS .In long-term follow-up, lung function in copper miners working underground at various workplaces was similar. Nevertheless, in cross-sectional analysis, a significant association between the type of job and lung function appeared after 20 years of work. Additionally, as soon as after 10 years of work, discrete obstructive type disturbances appeared in welders. This may be associated with smoking (the proportion of smokers in this group of miners compared with other groups was higher). Also, welding gases containing nitrogen oxides can affect airway flow in these workers, especially as, after 20 years of work, interactions between workplace and smoking were found. Thus, it should be emphasized that smoking welders should be referred to early clinical diagnostics.


Although the link between education and alcohol consumption is known, limited information exists on racial differences in this link. We conducted the current study to test Black–White differences in the association between education and alcohol consumption among older adults in the U.S.n = 734) and White (n = 759) older adults (age 66 or more) in U.S. Data came from the Religion, Aging, and Health Survey, 2001. Race, demographics, socioeconomics, and alcohol consumption were measured. Independent variable was education level. Outcome was alcohol consumption. Race was the focal moderator. Logistic regression was used for data analysis.This cross-sectional survey enrolled 1,493 Black  shapes behaviors, especially health behaviors . How race modifies consequences and correlates of social determinants of health is not yet clear. College graduation may result in the same level of change to the social network and income of race group members. Weaker effect of education on health of Blacks may be due to the structural role of race and racism that has resulted in lower job availability and pay for Blacks. Alcohol research literature has shown a U-shaped relationship between alcohol consumption and mortality risk, suggesting that alcohol consumption is associated with desired and undesired health outcomes, depending on the pattern of use. While compared with those who rarely or never drink, consuming up to one drink per day reduces the mortality risk ; heavy aAlcohol-related mortality is more common among lower socioeconomic status (SES) groups . AlcoholDrinking patterns and drinking outcomes are both shaped by the individuals’ SES –10. EducSimilar to many other parts of the world, SES is a major social determinant of drinking in American society , 15. In Race and ethnicity also influences the pattern of alcohol use in the U.S. . While BIn the U.S., race is one of the main determinants of employment opportunities and employer choices –25. StruIn addition to different employment opportunity, profits for equal jobs are different for Blacks and Whites, a phenomenon called Black–White pay gaps . Some ofThe protective effect of education on health is conditional on the availability of other resources – such as income and wealth – which are under influence of race –34.1 TheRace changes the health effects of education . WilliamBased on the differential effect hypothesis , correlaThis was a cross-sectional study with 3 years of follow-up data. Data came from Wave 1 of the Religion, Aging, and Health Survey, 2001, a nationally representative household survey of Black and White older adults in the U.S. .The study protocol was approved by the University of Michigan Institutional Review Board (IRB). All participants provided consent. Data were collected anonymously.The study only included White or Black older adults. All participants were non-institutionalized English-speaking people of age more than 65 years. The study population was limited to Christians or those who were never associated with any faith. Older Blacks were oversampled in the survey.Age (continuous measure), gender , race , income (continuous measure), education , and drinking (binary outcome) were measured.Following items were used to measure education: (1) did you get a high-school diploma or pass the high-school equivalency test? and (2) did you graduate from college and receive a bachelor’s degree? We treated our education variable as a three-level categorical variable: (0) less than high-school diploma [reference group], (1) completed high-school diploma, and (2) graduated from college.Participants were asked: here is a card showing amounts of yearly income. Into which of these groups did (your/your family’s) total income, from all sources, fall last year, 2000, before taxes? Responses included (1) less than $5,000, (2) $5,001–$9,999, (3) $10,000–$14,999, (4) $15,000–$19,999, (5) $20,000–$24,999, (6) $25,000–$29,999, (7) $30,000–$39,999, (8) $40,000–$59,999, (9) 60,000–$79,999, and (10) $80,000+. This variable was operationalized as a continuous measure, ranging from 1 to 10.Three items were used to assess drinking behavior. Items included (1) do you ever drink beer, wine, or liquor?, (2) during the last month, on how many days did you drink beer, wine, or liquor?, and (3) on the days you drink, how many cans of beer, glasses of wine, or drinks of liquor do you usually have? Our main outcomes were ever drinking, current drinking (last month), and problem drinking (5+ drinks per day), treated as three separate binary outcomes. Similar items have been shown to provide valid and reliable measures to study drinking patterns –55.We used SPSS 20.0 for data analysis. We fitted logistic regressions in the pooled sample , and specific to race, with education (socioeconomics) as the independent variable, ever drinking as the outcome, demographics (age and gender) as the covariates, and race as the focal moderator. We did not fit models for problem drinking as outcome, due to very limited number of individuals who reported five or more drinks per day. Odds ratios with 95% confidence intervals (CI) were reported.n = 734) and Whites (n = 759). Table The study enrolled 1,493 older individuals (age 65 or more). This number is composed of Blacks  that require diagnosis by a clinician or detailed structured interview. Third, although some covariates were controlled, we did not control for other potential covariates, including health, function, mood, and access to medical care. Lack of data on cognitive function was another limitation. This is particularly important given the protective effects of light-to-moderate alcohol consumption against dementia and cognitive decline in older adults –78. DespOverall, our findings suggest that Black–White differences exist in the association between college graduation and drinking among older adults in the U.S. Further research is needed to better understand the mechanisms behind race and ethnic differences in behavioral correlates of SES.All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation  with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all participants who were included in the study. University of Michigan Institutional Review Board (IRB) approved the study protocol.All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation  with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all participants who were included in the study.SA designed and analyzed this work, and contributed to draft and revision. ML contributed to design and revised the paper. All authors confirmed the last version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Cerebral palsy (CP) is a non-progressive CNS disorder due to an insult to the growing brain, usually occurring in the first two years of life. During the recent years, its etiology has been changed; perinatal and postnatal insults are not considered as its main causes in developed countries any more. The aim of this study was to evaluate the causes of CP in children in southern Iran.Overall, 200 children with CP aged 1-12 yr old referring to Pediatric Neurology Clinic affiliated to Shiraz University of Medical Sciences, Shiraz, Iran between 2012 and 2013 were enrolled. In addition, 200 healthy age and sex-matched children were considered as the control group. Exclusion criteria were isolated movement disorders with no other evidence of CP, progressive neurologic disorders, metabolic disorders, and incomplete or uncertain past history. After collecting the data on pregnancy period, prenatal history and past medical problems, they were analyzed with appropriate statistical methods.Maternal age, medical problems during pregnancy period, route of delivery, head circumference at birth, neonatal admission, neonatal jaundice, and prematurity were the main risk factors for CP.The distribution of risk factors of CP is different from that of developed countries in our region. Pre- and peri-natal etiologies are still among the common causes of CP in Iran. Cerebral palsy (CP) is a neurodevelopmental disorder usually occurring early in life and persisting thorough the life. According to the last proposed definition and classification of cerebral palsy “CP describes a group of permanent disorders of movement and posture causing activity limitation attributed to non-progressive disturbance in the developing fetal or infant brain”. Motor disorders are often accompanied by disturbance of sensation, perception, cognition, communication, and behavior as well as by epilepsy and secondary musculoskeletal problems . Risk faOverall, 200 patients aged 1-12 yr old with previously confirmed diagnosis of CP, according to international definitions (The mean age of the case group was 2.7±2.2 (range from 1 to 12 yr) and in the control group, it was 2.2±1.7 yr. The patients of case and control groups were equally divided into 51% male and 49% female groups . Spastic CP was the most prevalent type of CP in the case group (61%). The most common form was spastic quadriplegia . PrenataDuring recent years, pre- and peri-natal health care has been improved dramatically; as the result, asphyxia and other perinatal complications are no longer prevalent as previous years. However, premature and low birth weight neonates survive more. Therefore, the net incidence of CP, in fact, does not seem to be reduced but the etiologies have been changed , 14. Mat


Metastases to the breast from extramammary malignancies are very rare, and ruling out the diagnosis of primary breast tumor is important in order to decide on clinical management and predict prognosis.Clinical examination revealed in a 49-year-old hairdresser a 3-cm hard lump adherent to the underlying layers in the right breast. Trucut biopsy was performed. Histology showed a solid proliferation of medium-sized neoplastic polygonal cells. Immunohistochemical analysis showed tumor cells diffusely positive for cytokeratin 8/18 and calretinin and focally positive for cytokeratin 5/6 and Wilms’ tumor 1, e-cadherin, and human bone marrow endothelial-1. Estrogen receptors and progesterone receptors were negative. The final diagnosis was metastatic epithelioid malignant pleural mesothelioma.Immunohistochemistry is an important tool for a conclusive diagnosis of malignant pleural mesothelioma. Owing to the degree of histological and immunohistochemical overlap, a high level of clinical suspicion is essential in order to avoid unnecessary mutilating surgery. Breast cancer is the most common malignancy in women, whereas metastases to the breast from extramammary malignancies are very rare, accounting for only 0.43% of all malignant breast tumors . The mosMalignant pleural mesothelioma (MPM) is a rare and aggressive tumor with a median survival of 4 to 12 months, officially recognized as an occupational disease and a signal disease for asbestos exposure . More thWe report an unusual case of a woman presenting with a breast mass in which trucut biopsy under ultrasound guidance enabled assessment of metastatic MPM.A 49-year-old hairdresser was referred to our Breast Unit for suspected right breast cancer. A family history of breast cancer in a first-degree relative was reported. The patient had no symptoms, such as fever, night sweats, cough, and chest pain. Clinical examination revealed a 3-cm hard lump adherent to the underlying layers in the right breast and extending into the axillary tail. Breast sonography showed a solid polylobated mass (3 × 2.5 cm) with heterogeneous echogenicity and no acoustic shadowing behind the tumor. Mammograms were difficult to interpret due to high breast density. Trucut biopsy was performed.Histology showed a solid proliferation of medium-sized neoplastic polygonal cells bearing large round vesicular nuclei with central nucleoli and moderate amounts of pale, pinkish cytoplasm. There was little intervening fibrillary stroma and no breast parenchyma Figure . ImmunohIn order to confirm the diagnosis and assess thoracic extension, computed tomography (CT) of the chest was performed revealing a parenchymatous neoformation (6 cm) in the right parietal pleura and a lump near the right axilla 3 cm)  performed on the male breast from 1985 to 1992. One case of metastatic MPM was found [et al. reported a case of a 51-year-old woman with a large pleural mesothelioma and an irregular left breast lesion (4 × 3.5 cm), which proved to be a metastatic deposit. Further immunohistochemical study was performed, and the tumor cells were positive for low and high molecular weight cytokeratin and thrombomodulin and focally positive for CEA [et al. presented a case of a 60-year-old male patient with a right breast mass (13 cm) found to be a metastatic MPM. Immunohistochemistry showed a strong positive expression of calretinin, epithelial membrane antigen, WT1, pan-cytokeratin, thrombomodulin, anti-D240 antibody (D2-40), e-cadherin, and CK 5, 6, and 7 [Only five cases of metastatic MPM presenting with a breast mass as the initial sign of the disease are reported in the literature, two of them affecting male patients. Ribeiro-Silva ial sign ,8. Sneig for CEA . More re6, and 7 .Breast metastasis was the first manifestation of MPM in our patient. The histopathological appearance of MPM varies and may therefore be a diagnostic challenge, particularly in the presence of a biopsy specimen of an unrelated site. The 2004 World Health Organization (WHO) classification includes three histological subtypes: epithelioid, sarcomatoid, and biphasic mesothelioma. Rare variants are desmoplastic type, undifferentiated type, and deciduoid type. The entirely solid microscopic architecture of the present lesion and the absence of mammary parenchyma in the biopsy specimen raised suspicion of primary non-breast malignancy and prompted further investigation, which led to the correct diagnosis.Immunohistochemistry is an important tool for a conclusive diagnosis of MPM. The main positive MPM markers include calretinin, WT1, CK 5/6, and HBME-1, whereas gross cystic disease fluid protein 15 (GCDFP-15) and mammaglobin are used to confirm breast cancer, although these markers may be only focally positive depending on the antibody clone used as well as the hormone receptor status of the tumor .As reported in Case presentation section the tumor cells were diffusely positive for calretinin and CK 8/18 and focally positive for CK 5/6, WT1, e-cadherin, and HBME-1.Calretinin shows strong nuclear and/or cytoplasmic positivity in mesothelial cells and is expressed in epithelioid MPM, but not in the sarcomatoid variant of MPM. However, calretinin expression is not exclusive to MPM  as it isin situ carcinoma is diffusely positive for this luminal cell marker [CK 8/18 is a low molecular weight cytokeratin found in simple epithelium and secretory epithelium. CK 8/18 is markedly upregulated in epithelioid MPM, whereas only ductal l marker . AccordiCK5/6 is a basal cell marker, which is expressed in only 10 to 15% of breast tumors, predominantly in basal-like carcinoma, metaplastic carcinoma, and adenoid cystic carcinoma. In contrast, 75 to 100% of MPMs are CK 5/6-positive [Approximately 75 to 80% of breast tumors are positive for ER and/or PR, but MPMs are not. However, this percentage is reduced to only 2% in breast cancer nuclear grade 3. The present lesion was negative for ER and PgR .Approximately 15% of breast primary cancers of the papillary mucinous subtype are positive for WT1, an independent marker for mesothelioma . Howeveret al. [E-cadherin is normally expressed in the cell membrane of breast ductal cancer cells but not in mesothelial cells. Nevertheless, the present tumor presented focal positive immunostaining, like the case reported by Aujayeb et al. , therebyHBME-1 normally reacts with an antigen present in the membrane of benign and malignant mesothelial cells, and it was focally expressed in our case. However, sensitivity of HBME-1 is high while specificity is low in mesothelial differentiation, as this marker stains various types of adenocarcinoma. HBME-1 is also nonreactive with sarcomatous mesothelioma and with the sarcomatous components of the biphasic variants .Ber-EP4, thrombomodulin, and CEA were negative in this case. Ber-EP4 and CEA are expected to be negative in MPM, but the negativity for thrombomodulin was surprising, considering that the reported sensitivity and specificity of thrombomodulin in epithelioid mesothelioma range from 61% to over 80% .According to the limited data reported in the literature, mesothelioma is immunonegative for both mammaglobin and GCDFP-15. Confirmation of breast origin may therefore be obtained using immunostaining with mammaglobin, GCDFP-15, and androgen receptor in difficult cases, which seem to fit into the triple-negative category of breast carcinoma .In conclusion, as symptomatic metastases of MPM are unusual and metastases to the breast are very rare, clinical and histological misdiagnosis is possible. Owing to the degree of histological and immunohistochemical overlap, a high level of clinical suspicion is essential in order to avoid unnecessary mutilating surgery. A large panel of immunoreactions is necessary to establish a correct diagnosis. We found that CK 8/18, CK 5/6, and WT1 formed a useful panel in this respect, particularly if associated with negative results for ER and PR.Despite the metastatic disease and the refusal of treatment, this patient is still alive after 9 months, possibly due to the favorable epithelioid histology of the tumor, which is associated with the longest survival .Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.


Infected nonunion of tibia and femur are common in clinical practice, however, the treatment of these diseases has still been a challenge for orthopaedic surgeons. Ilizarov methods can eradicate infection, compensate bone defects and promote the bone union through progressive bone histogenesis. The objective of this systematic review was to review current available studies reporting on Ilizarov methods in the treatment of infected nonunion of tibia and femur, and to perform meta-analysis of bone and functional results and complications to evaluate the efficacy of Ilizarov methods.A comprehensive literature search was performed from the SCI, PubMed, Cochrane Library; and Embase between January 1995 and August 2015. Some major data were statistically analyzed using weighted means based on the sample size in each study by SPSS 13.0, including number of patients, mean age, mean previous surgical procedures, mean bone defects, mean length of follow-up, bone union, complications per patient, external fixation time, and external fixation index(EFI). Bone results , functional results  and complications were analyzed by Stata 9.0.2 = 44.1%, P = 0.065) and 10%  in patients with infected nonunion of tibia and femur treated by Ilizarov methods. The rate of refracture, malunion, infectious recurrence, knee stiffness, amputation, limb edema and peroneal nerve palsy was respectively 4%, 7%, 5%, 12%, 4%, 13% and 13%.A total of 590 patients from 24 studies were included in this systematic review. The average of bone union rate was 97.26% in all included studies. The poor rate in bone results and functional results was 8% (95%CI, 0.04–0.12; IOur systematic review showed that the patients with infected nonunion of tibia and femur treated by Ilizarov methods had a low rate of poor bone and functional results. Therefore, Ilizarov methods may be a good choice for the treatment of infected nonunion of tibia and femur. Some . Several. Moreove, at the .Ilizarov methods base on the principles of distraction osteogenesis. It entails a segmental bone transport in which corticotomy is performed in the metaphysis and the bone is gradually distracted. Application of Ilizarov methods in the treatment of an infected nonunion depends on the extent of infection, the type of infected nonunion and the condition of the soft tissues. In ordeUp to now, there are numerous reports on the treatment of infected nonunion of tibia and femur by Ilizarov methods, and it has gradually been a main treatment for infected nonunion. Although infected nonunion treated by Ilizarov methods acquired a satisfactory outcome in most studies, there were still some relative dissatisfactory results in several studies ,12. In aWe did serial literature searches for relevant studies according to the guidelines from the Cochrane Collaboration. The following databases were searched: SCI (January 1995 to August 2015), PubMed (January 1995 to August 2015); Cochrane Library (January 1995 to August 2015); and Embase (January 1995 to August 2015).Keywords used to identify relevant articles were ‘infected’ or ‘infection’, ‘nonunion’, ‘non-union’, ‘tibia’, ‘femur’, ‘Ilizarov method’ or ‘Ilizarov methods’, and ‘Ilizarov technique’ or ‘Ilizarov techniques’. We used MeSH terms including ‘infection’, ‘tibia’, ‘femur’, and ‘Ilizarov technique’.The following eligibility criteria were performed in articles selection: (1) target population: patients with infected nonunion of tibia and femur; (2) intervention: Ilizarov methods, including bone transport, acute compression and lengthening, and compression osteosynthesis; (3) outcomes: bone union, bone results evaluated by ASAMI, functional results evaluated by ASAMI, complications, external fixation time and external fixation index. The eligible study included two above-mentioned outcomes at least; (4) article types: any type of the articles, excluding case report and review; (5) language restriction: articles written in the English language. We did the language restriction in order to avoid translation costs. Duplicate or multiple publications of the same study were excluded. We also excluded studies involving animal models, children, basic research, and when it was impossible to extract or calculate the data of infected nonunion from the studies.All relevant data that met the eligibility criteria were independently and separately extracted by two authors. Discrepancies were resolved by discussion with each other. The following data were extracted from each included study: first author, publication year, study design, technique, site of infected nonunion, number of patients, mean age, mean previous surgical procedures, mean bone defects, mean length of follow-up, bone union, bone results evaluated by ASAMI, functional results evaluated by ASAMI, complications per patient, external fixation time, and external fixation index(EFI), complications .Bone results , functional results  and complications were analyzed by using STATA 9.0. Differences were expressed as effect size (ES) with 95% CIs for the rate meta-analysis. Heterogeneity among studies was tested by using the standard chi-square test(with significance defined as P<0.1), and the I-square test . A randoThe initial literature search identified 243 relevant records published from January 1995 to August 2015. 30 studies remained after screening by reading titles and abstracts. Ultimately, 24 studies met the inclusion and exclusion criteria in the systematic review by reviewing the full-text articles1,7,8,10–31.Of thThe systematic review included a total of 590 patients with infected nonunion of tibia and femur treated by Ilizarov methods. The mean age of all patients was 33.79 years; the mean age was 34.11 years in patients with infected tibia nonunion and 32.68 years in patients with infected femur nonunion. The patients had an average of 3.64 previous surgical procedures before receiving the treatment of Ilizarov method,27,29–31The interventions mainly included three parts: radical debridement, antibiotic treatment, and Ilizarov methods. Ilizarov methods included three techniques: bone transport, acute compression and lengthening, and compression osteosynthesis. Flap transfer was reported in 2 included studies ,28. BoneThe average of bone union rate was 97.26% in all included studies, and 97.50% in the studies of infected tibia nonunion and 97.59% in the studies of infected femur nonunion. The mean complications of every patient were 1.36 in all patients, and 1.23 in patients with infected tibia nonunion and 2.24 in patients with infected femur nonunion. The mean external fixation time was 10.69 months in the patients–28,30,31The criteria recommended by ASAMI were adopted to evaluate bone results and functional results in the studies,27,29,31Bone results were evaluated in 16 studies by ASAMI –24,29,31Functional results were reported in 16 studies ,27,29,31Complications were summarized in 2 = 44.1%, P = 0.065) and 10% . The data were not statistically heterogeneous. Therefore, our results showed that the patients with infected nonunion of tibia and femur treated by Ilizarov methods had a low rate of poor bone and functional results.This is the first systematic review of infected nonunion of tibia and femur treated by Ilizarov methods. The systematic review included 24 studies, and we conducted a meta-analysis of 16 studies to evaluate the efficacy of Ilizarov methods in the treatment of infected nonunion of tibia and femur. The poor rate in bone results and functional results was 8%  and 9% . The rate of bone grafting, knee stiffness, malunion, refracture, infectious recurrence, limb edema, amputation and Peroneal nerve palsy was respectively 14%, 13%, 7%, 4%, 6%, 13%, 4% and 13%. These data were not statistically heterogeneous.In our systematic review, most studies involved infected tibia nonunion, and we performed subgroup analysis based on the sites of infected nonunion. The data of infected tibia nonunion could be found in Tables To our best knowledge, this is the first systematic review of infected nonunion of tibia and femur treated by Ilizarov methods. We were able to provide a large number of data on characteristics of patients and treatment results through 24 included studies. We also conducted meta-analyses of bone and functional results in our systematic review. High heterogeneity existed in several pooling data in our study, and we thought the heterogeneity was probably resulted from different research quality, various surgeons’ experience and diversity of rehabilitation nursing. Failure to include the non-English language studies in our article could have resulted in missing data and our estimates of effect size might have been biased, nevertheless, 24 studies were included in our article and they were not unduly affected by significant statistical heterogeneity. The data of the present review were extracted from observational studies, which are prone to cause both systematic and random error –37. TherIn conclusion, our systematic review showed that the patients with infected nonunion of tibia and femur treated by Ilizarov methods had a low rate of poor bone and functional results. Therefore, Ilizarov methods may be a good choice for the treatment of infected nonunion of tibia and femur.