Positive Sample Rate Research Articles

Abstract 3907: Novel public and tumor-wide neoantigens arising from clonal aberrant splicing events drive tumor-specific T-cell responses across diverse cancer types

Abstract BACKGROUND: Immunotherapy in gliomas is limited by intratumor heterogeneity (ITH) and low mutational burden. We developed a novel comprehensive in silico pipeline for detecting tumor-specific splicing events (neojunctions), and across multiple cancer types, we successfully identified a new class of tumor-wide, public, alternatively spliced neoantigens (ASNs) that elicit CD8+ T-cell-mediated immune responses. METHODS: Our pipeline identified recurring public neojunctions expressed in TCGA RNA-seq (positive sample rate (PSR) > 10%) and not in GTEx normal tissue RNA-seq data (PSR < 1%) across ten cancer types. To characterize tumor-wide neojunctions, we utilized available multi-site RNA sequencing across diverse cancer types. With gliomas, our in-house dataset comprised of 56 patients with approximately 10 maximally-distanced intratumoral biopsy sites per patient (n=535). Tumor-wide public neojunction expression was subsequently validated in RNA-sequencing and mass spectrometry (MS) data from patient-derived cell lines (n=68) and samples (n=447). Two independent algorithms then predicted peptide processing likelihood and HLA-binding affinity of ASN candidates. TCRs identified by in vitro sensitization (IVS) of donor-derived CD8+ T-cells followed by 10x VDJ scRNA-seq, were transduced into CD8+ T-cells and co-cultured with tumor cells to evaluate TCR functionality and cytotoxicity. RESULTS: Pan-cancer analysis identified large subsets of neojunctions that were interpatiently and intratumorally conserved. Our glioma-specific analysis identified 789 public neojunctions, and 8 ASNs were validated in transcriptomic and proteomic glioma data and predicted to be presented by HLA-A*02:01 with high confidence. IVS and subsequent 10x VDJ scRNA-seq on expanded PBMC-derived CD8+ populations cultured against ASN-pulsed dendritic cells identified TCR clonotypes reactive against neojunctions in RPL22 (n=7) and GNAS (n=1), the latter being highly intratumorally-conserved (detected in > 90% of spatially-mapped biopsies in 17/56 patients (26.78%)). TCR-transduced T-cells demonstrated recognition and immunogenic activation against endogenously processed and presented neoantigens in both pan-cancer cell lines and transfected COS7 cells and cytotoxicity against glioma cell lines. Pan-cancer analysis revealed the detection of both neojunctions in various tumor types beyond gliomas, with the GNAS neojunction notably found tumor-wide in mesothelioma, prostate cancer, and liver hepatocellular carcinoma spatial data. CONCLUSION: Our unique integrative pipeline identified a novel class public tumor-wide splice-derived neoantigen candidates and ASN-specific TCRs, offering a promising off-the-shelf immunotherapy approach for diverse cancer types and tackling the critical challenge of ITH in immunotherapy resistance. Citation Format: Darwin Kwok, Nicholas O. Stevers, Takahide Nejo, Lee H. Chen, Inaki Etxeberria, Jangham Jung, Kaori Okada, Maggie Colton Cove, Senthilnath Lakshmanachetty, Marco Gallus, Abhilash Barpanda, Chibo Hong, Gary KL Chan, Samuel H. Wu, Emilio Ramos, Akane Yamamichi, Jerry YZ Liu, Payal Watchmaker, Hirokazu Ogino, Atsuro Saijo, Aidan Du, Nadia Grishanina, James Woo, Aaron Diaz, Susan M. Chang, Joanna J. Phillips, Arun P. Wiita, Christopher A. Klebanoff, Joseph F. Costello, Hideho Okada. Novel public and tumor-wide neoantigens arising from clonal aberrant splicing events drive tumor-specific T-cell responses across diverse cancer types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3907.

IMMU-16. PUBLIC TUMOR-WIDE NEOANTIGENS DERIVED FROM CLONAL ABERRANT SPLICING EVENTS DRIVE TUMOR-SPECIFIC T-CELL RESPONSES

Abstract BACKGROUND Immunotherapy in gliomas is limited by tumor heterogeneity and low mutational burden. We developed a novel comprehensive in silico pipeline for detecting tumor-specific splicing events (neojunctions) across multiple cancer types, and in gliomas, we successfully identified tumor-wide, public, alternatively spliced neoantigens (ASNs) that elicit CD8+ T-cell-mediated immune responses. METHODS Our pipeline identified recurring public neojunctions expressed in TCGA RNA-seq (positive sample rate (PSR) > 10%) and not in GTEx normal tissue RNA-seq data (PSR < 1%) across six cancer types. To characterize intratumorally-conserved neojunctions, we utilized multi-site RNA sequencing, and with gliomas, we analyzed approximately 10 maximally-distanced intratumoral sites within 56 patients (n=535). Tumor-wide public neojunction expression was subsequently validated in RNA-sequencing and mass spectrometry (MS) data from patient-derived cell lines (n=68) and samples (n=99). Two independent algorithms then predicted peptide processing likelihood and HLA-binding affinity of ASN candidates. In vitro sensitization (IVS) of healthy donor-derived CD8+ T-cells against high-confidence ASN candidates, followed by 10x VDJ scRNA-seq, was performed to identify ASN-specific TCR sequences. TCRs were transduced into triple-reporter Jurkat76s and co-cultured with ASN and HLA-expressing COS7 cells and glioma cell lines to evaluate TCR functionality. RESULTS Our glioma-specific analysis identified 249 public neojunctions with varying intratumoral heterogeneity. 4 ASNs were concurrently identified in transcriptomic and proteomic glioma data and predicted to be presented by HLA-A*02:01 with high confidence. IVS and subsequent 10x VDJ scRNA-seq on expanded CD8+ populations identified TCR clonotypes reactive against neojunctions in RPL22 (n=7) and GNAS (n=1), the latter being highly intratumorally-conserved (detected in > 90% of spatially-mapped biopsies across 17/56 patients (26.78%)). TCR-transduced T-cells demonstrated recognition and immunogenic activation against endogenously processed and presented neoantigens in glioma and transfected COS7 cells. CONCLUSION Our unique integrative pipeline identified novel public tumor-wide splice-derived neoantigen candidates and TCRs, offering a promising off-the-shelf immunotherapy approach for gliomas.

Yield of Emergency Department Stool Culture Tests Among Children With Acute Gastroenteritis in Israel.

Previous studies have attempted to predict a positive stool culture in pediatric patients with acute gastroenteritis (AGE), but most of them are either from developing countries or are outdated. In all, 276 patients with AGE and 560 control patients were analyzed for differences in clinical factors including the presence of fever, highest recorded temperature, bloody diarrhea, number of bowel movements in 24 hours prior to presentation, and the presence of seizures, as well as laboratory parameters including leukocyte count and C-reactive protein (CRP). Positive stool sample rate was 13.7%. The most common bacterial pathogen was Campylobacter jejuni. Bacterial AGE was significantly associated with fever >37.9°C, bloody diarrhea, higher stool passing frequency, seizures, and CRP levels. For pediatric patients who present to the emergency department with AGE and present without bloody diarrhea, fever, frequent stool passing, or seizures, a stool culture test is of poor yield and may not be necessary.

First Report of Apiospora Mold on Sugarcane in China Caused by Apiospora arundinis (Arthrinium arundinis).

Sugarcane (Saccharum officinarum L. cv. Badila) is a chewing cane cultivar in southern China. Since the first case of poisoning caused by the consumption of moldy sugarcane was confirmed in northern China in 1972, cases have occurred almost every year. It has been confirmed that Arthrinium is the pathogen that primarily occurs during improper postharvest storage (Liu xingjie, 1984). In 2019, ten moldy sugarcane stems (cv. Badila) were collected from Tang County, Baoding City, Hebei Province, China. The sugarcane flesh turned dark and was grayish-white, red, or reddish-brown. Some of them smelled musty. Symptomatic stems were surface disinfected using 75% ethanol and peeled aseptically. Small sections (3 mm3) were placed on potato dextrose agar amended with 0.01% chloramphenicol and incubated at 26 ± 2°C. Six fungal isolates were obtained from three sugarcane stems, a positive sample rate of 30%, and identified as the same fungus on the basis of morphological features owing to their formation of flat colonies that were initially white and later turned grayish white with moderate amounts of aerial mycelia. The mycelia consisted of smooth, hyaline, branched, and septate hyphae. The conidiophores were hyaline or pale brown and produced conidiogenous cells. The conidiogenous cells were pale brown, smooth, ampulliform, and 5.5 to 11.2 μm long (n=50). The conidia were brown, smooth, ellipsoidal to spherical, spherical in surface view, 4.5 to 7.4 μm in diameter, and 3.3 to 4.4 μm wide with a pale equatorial slit (n=50). The morphological characteristics of the one representative isolate, named LX1918, were identical to those of Arthrinium arundinis (Corda) Dyko & B. Sutton (Apiospora arundinis (Corda) Pintos & P. Alvarado) (Crous and Groenwald, 2013, Pintos and P. Alvarado, 2021). Genomic DNA was extracted from the mycelia to further identify the isolate. The internal transcribed spacer region (ITS rDNA), the translation elongation factor 1-alpha gene (TEF1) and the ß-tubulin gene (TUB2) were amplified using the primers ITS1/ITS4, EF1-728F/ EF-2 and T1/ Bt2b (White et al., 1990, O'Donnell et al. 1998, O'Donnell et al. 1997), respectively. BLASTn analysis of the ITS (556 bp, GenBank accession no. MW534386), TEF (434 bp, MW584370) and TUB2 (775 bp, MZ090019) sequences of isolate LX1918 showed that they were 99.43%, 99.52% and 99.74% similar to the published sequences of isolate CBS 106.12 (KF144883, KF145015 and KF144973), respectively. To confirm Koch's postulates, pathogenicity tests were conducted in triplicate by inoculating the aseptic wounds with a conidial suspension (105/ml) of the isolate in healthy sugarcane stems. The controls were inoculated with sterile water. The sugarcane stems were incubated at 26 ± 2 °C and 86 % relative humidity in the dark. Obvious moldy symptoms appeared several days after the sugarcane stems had been inoculated. The sugarcane flesh turned reddish brown. In contrast, the control stems were asymptomatic. Ap. arundinis (Ar. arundinis) was reisolated from the inoculated and moldy sugarcane. In addition, 3-nitropropionic acid could be detected using HPLC-MS after the fungus had been cultured on potato yeast sucrose agar for 14 days. Previous studies had confirmed that 3-nitropropionic acid produced by Ar. sacchari, Ar. saccharicola and Ar. phaeospermum is the causal agent of poisoning caused by the consumption of moldy sugarcane (Hu wenjuan, 1986, Liu xingjie,1987). To our knowledge, this is the first report of Ap. arundinis (Ar. arundinis) as the causal agent of infected sugarcane and its production of 3-nitropropionic acid, which is toxic to humans. Therefore, the confirmation that Ap. arundinis(Ar. arundinis) infects sugarcane will expand our understanding of this pathogen and provide fundamental knowledge about the control of Apiospora mold to decrease the incidents of 3-nitropropionic acid poisoning.

High prevalence of malaria in a non-endemic setting among febrile episodes in travellers and migrants coming from endemic areas: a retrospective analysis of a 2013\u20132018 cohort

BackgroundThe study aimed to analyse the likelihood of imported malaria in people with a suggestive clinical picture and its distinctive characteristics in a hospital in the south of Madrid, Spain.MethodsObservational retrospective study that consisted of a review of all medical files of patients with any malaria test registered at Móstoles University Hospital between April 2013 and April 2018. All suspected malaria cases were confirmed by Plasmodium spp. polymerase chain reaction (PCR).ResultsOf the 328 patients with suspected malaria (53.7% migrant-travellers; 38.7% visitors; 7.6% travellers), 108 cases were confirmed (101 by Plasmodium falciparum), accounting for a 33% positive sample rate. Sixteen cases were diagnosed only by PCR. Patients with malaria, compared to those without, presented predominantly with fever (84% vs. 65%), were older (34 vs. 24 years), sought medical attention earlier (17d vs. 32d), had a greater number of previous malaria episodes (74% vs. 60%), lower levels of platelets (110,500µL vs. 250,000µL), and higher of bilirubin (0.6 mg/dL vs. 0.5 mg/dL). Severe malaria was present in 13 cases; no deaths were recorded. Malaria diagnosis showed a bimodal distribution with two peaks: June to September and November to January.ConclusionsMalaria is still a common diagnosis among febrile patients coming from the tropics specially among migrant travellers. Fever, thrombocytopenia, and/or high bilirubin levels should raise suspicion for this parasitic infection. Prompt diagnosis is crucial to avoid severe cases and deaths.

Virulence of new strain of Heterorhabditis bacteriophora from Croatia against Lasioptera rubi

Soil samples from 100 cultivated and natural sites were assessed for the presence of entomopathogenic nematodes. Heterorhabditid nematodes were recovered from three soil samples during spring months, with the overall positive sample rate of 3%. The isolates of entomopathogenic nematodes were identified as three different strains conspecific with Heterorhabditis bacteriophora (Heterorhabditidae). They were found from natural sites and vineyard, while no recovery occurred from intensively cultivated agricultural fields. The morphometrical characteristics of infective juveniles and males showed differences between all Croatian strains and from the original description. Heterorhabditis bacteriophora ISO9 was bioassayed on Lasioptera rubi (Cecidomyiidae) (the raspberry gall midge) larvae at different nematode concentrations under laboratory conditions. The significantly highest mortality was observed in treatments with 50 and 200 infective juveniles per insect larvae within 8 days after inoculation. This is the first report of entomopathogenic nematodes of the family Heterorhabditidae from Croatia, and susceptibility of L. rubi larvae to entomopathogenic nematodes. The Croatian strain H. bacteriophora ISO9 was proved to possess strong insecticidal properties against L. rubi larvae.

Epidemiological survey and sequence information analysis of swine hepatitis E virus in Sichuan, China.

Hepatitis E is an important zoonosis that is prevalent in China. Hepatitis E virus (HEV) is a pathogen that affects humans and animals and endangers public health in China. In this study, the detection of HEV epidemics in swine in Sichuan Province, China, was carried out by nested real-time PCR. A total of 174 stool samples and 160 bile samples from swine in Sichuan Province were examined. In addition, software was used to analyse the biological evolution of HEV. The results showed that within 2 years of swine HEV (SHEV) infection in China, SHEV was first detected in Sichuan Province. HEV was endemic in Sichuan; the positive rate for pig farms was 11.1%, and the total positive sample rate was 10.5%. The age of swine with the highest positive rate (17.9%) was 5-9 weeks. The examined swine species in order of highest to lowest HEV infection rates were Chenghua pig, Large White, Duroc, Pietrain, Landrace and Hampshire. Nucleotide and amino acid sequence analysis showed that the HEV epidemic in swine in Sichuan Province was related to genotype IV, which had the highest homology to HEV in Beijing. Sichuan strains have greater variation than Chinese representative strains, which may indicate the presence of new HEV strains.

Insights into the epidemic characteristics and evolutionary history of the novel porcine circovirus type 3 in southern China.

Porcine circovirus type 3 (PCV3) is a newly identified circovirus from swine in the USA, China and Poland. This novel circovirus has been associated with porcine dermatitis and nephropathy syndrome (PDNS), reproductive failure and multisystemic inflammation; moreover, PCV3 poses a potential threat to the swine industry. In this retrospective study, a phylogenetic analysis was conducted to address the epidemiology and evolutionary dynamics of this novel circovirus. The total positive sample rate of PCV3 was 26.7% (76/285) and has increased gradually over the past 3years. Of these PCV3-positive samples, 22.3% (17/76) were coinfected with PCV2. PCV3 can be detected in multiple sample types with different positive rates, and the positive rate is highest among stillborn. We also divide PCV3 into three clades (PCV3a, PCV3b and PCV3c) based on two amino acid mutations (A24V and R27K) on the cap protein in this study. In addition, the origin of PCV3 was approximately 1966 and may have originated from a bat-associated circovirus. Our results suggested that PCV3 is widely distributed in southern China and has been circulating in swine herds for nearly half a century. PCV3 has evolved into different clades caused by mutations in cap proteins; thus, further research on PCV3 epidemiology should be conducted.

Exploring transfer learning for gastrointestinal bleeding detection on small-size imbalanced endoscopy images.

The success of Convolutional Neural Network (CNN) is attributed to their ability to learn rich midlevel image representations as opposed to hand-crafted low-level features used in many natural image classification methods. Learning CNN, however, amounts to estimating millions of parameters and requires a very large number of annotated image samples. In this paper, we explored transfer learning for gastrointestinal bleeding detection on small-size imbalanced endoscopy images, and showed how image representations learned with CNN on large-scale annotated datasets can be efficiently transferred to other tasks with limited amount of training data. We first transferred pre-trained Inception V3 model trained on the ImageNet dataset to compute mid-level image representation, and then fine-tuned the trained model with labeled endoscopy images, and resumed training from already learned weights. Additionally, we introduce both data augmentation and image resampling to increase the size of the training database and the positive sample rate to perform the Transfer Learning. Our results showed that our transfer learning method produces the best performance on AUC (the area under the receiver operating curve), Precision, Recall and Accuracy as compared to both the hand-crafted feature based method and training CNN model from-scratch method.

Detection of avian influenza A(H7N9) virus from live poultry markets in Guangzhou, China: a surveillance report.

PurposeA virologic surveillance program for A(H7N9) virus was conducted from April 15, 2013 to February 14, 2014 in Guangzhou, aiming to clarify the geographical distribution of A(H7N9) viruses among live poultry markets (LPMs) and poultry farms in Guangzhou. Virological and serological surveys of poultry workers were also conducted to evaluate the risk of poultry-to-human transmission of the A(H7N9) virus.Methods36 retail LPMs, 6 wholesale LPMs and 8 poultry farms were involved in our surveillance program. About 20 live poultry and environmental samples were obtained from each surveillance site at every sampling time. Different environmental samples were collected to represent different poultry-related work activities. RT-PCR and virus culture were performed to identify the A(H7N9) virus. Hemagglutinin inhibition assay and RT-PCR were conducted to detect possible A(H7N9) infection among poultry workers.ResultsA total of 8900 live poultry and environmental samples were collected, of which 131(1.5%) were tested positive for A(H7N9) virus. 44.4% (16/36) of retail LPMs and 50.0% (3/6) of wholesale LPMs were confirmed to be contaminated. No positive samples was detected from poultry farms. A significant higher positive sample rate was found in environmental samples related to poultry selling (2.6%) and slaughtering (2.4%), compared to poultry holding (0.9%). Correspondingly, A(H7N9) viruses were isolated most frequently from slaughter zone. In addition, 316 poultry workers associated with the 19 contaminated-LPMs were recruited and a low seroprevalence (1.6%) of antibody against A(H7N9) virus was detected. An asymptomatic A(H7N9) infection was also identified by RT-PCR.ConclusionsOur study highlights the importance of conducting effective surveillance for A(H7N9) virus and provides evidence to support the assumption that slaughtering is the key process for the propagation of A(H7N9) virus in retail LPMs. Moreover, the ability of A(H7N9) virus to cross species barrier is proved to be still limited.

Overexpression of HER-2/neu in patients with prostatic adenocarcinoma.

Prostatic adenocarcinoma is one of the main causes of cancer death, and its timely diagnosis and preventing its progression dramatically helps improve life indexes. Given the high disease recurrence rate, today, research is more inclined toward exploring causes of recurrence and development, and innovation of modern treatment methods. Several studies have explored over-expression of human epidermal growth factor receptor 2 (HER-2/neu) in prostatic cancer so far, with different results. Thus, it was decided to investigate HER-2/neu overexpression in patients with prostatic adenocarcinoma in Iran. A sample size of 40 patients with prostate cancer entered the study, using a cross-sectional, non-randomized sampling method. Parameters studied included patient age at surgery, Gleason score, serum prostatic specific antigen (PSA) before surgery, and positive sample rate after immunohistochemical staining to investigate HER-2/neu overexpression. In terms of HER-2/neu receptor staining rate, of 40 slides, 16 (40%) scored 0, 13 (32.5%) 1+, 7 (17.5%) 2+, and 4 (10%) 3+. In total 27.5% of slides showed HER-2/neu overexpression. In terms of age, an inverse correlation was found (-0.181), but without significance (p=0.263). In terms of serum PSA, the correlation coefficient was 0.449 (p=0.004). With respect to Gleason score, the coefficient was 0.190 (p=0.240). In this study, HER-2/neu overexpression occurred in 27.5% of prostate cancer cases, which is a relatively high figure, compared to similar studies elsewhere. While, we failed to reveal any relationship between HER-2/neu expression status with progression and prognosis of disease, it was demonstrated that the serum PSA level was significantly higher in cases with increased receptor expression.

Estimation of ochratoxin A in some Turkish populations: An analysis in urine as a simple, sensitive and reliable biomarker

In this study, ochratoxin A (OTA) occurrence and level in human urine samples, collected from four different regions of Turkey was analyzed by NaHCO3 dilution, immunoaffinity column clean-up and high-performance liquid chromatography with fluorescent detection. For the repeatability of the method, RSD (%) values were found between 3.83 and 8.86, for the accuracy, the recovery values were found between 85.7% and 110.5% and limit of detection and limit of quantification of the method were measured as 0.006 and 0.018ngmL−1 respectively. For the analysis, first morning urine samples were collected and the results were adjusted with creatinine levels. From the total collected samples of 233 larger amounts of 83% was contaminated with OTA. Among the calculated to be OTA levels, positive sample rate, average OTA amount and the highest contamination was found in Ankara. (Positive sample rate; 90.1%, average OTA concentration; 14.34ngg−1 creatinine and highest OTA value; 75.60ngg−1 creatinine). In order to define the exposure profile of OTA in human a questionnaire was conducted among the voluntaries as well. But related to the gender, age, dietary habits, coffee consumption, smoking and alcohol habits of the volunteers, no correlation was found with the OTA exposure.

Biópsia transtorácica com agulha cortante (Trucut) para o diagnóstico dos tumores mediastínicos

Aim: To determine the contribution of percutaneous biopsy with core cutting needle (Trucut) in the diagnosis of mediastinal tumours. Method: Retrospective review of 56 patients with mediastinal lesions who underwent percutaneous core cutting needle biopsy, oriented but not guided by computer assisted tomography of the thorax, 1999 – 2008. Results: Percutaneous biopsy with core cutting needle provided adequate material in 49/56, with a total positive sample rate of 88%. In 7/56 (12%) cases the material was insufficient to define the diagnosis. Percutaneous core cutting needle biopsy established a specific histological diagnosis in 88% of the patients: 23/56 (41%) lymphomas; 12/56 (21%) thymomas; 5/56 (3%) thymic carcinomas; 3/56 (2%) small cell carcinoma and 1/56 (0.6%) metastatic adenocarcinoma, metastatic squamous cell carcinoma, neuroendocrine primitive carcinoma, plasmocytoma, teratoma and goiter. All patients underwent thoracic X-ray after the procedure. No complications were found in these patients. Conclusion: Percutaneous core cutting needle biopsy (Trucut) oriented but not guided by computer assisted tomography of the thorax is an easy and safe procedure which can provide a precise diagnosis in the majority of mediastinal tumours and can prevent the need for exploratory thoracic surgery in cases which are medically treatable or non-resectable.Rev Port Pneumol 2009; XV (4): 589-595

Transthoracic biopsy with core cutting needle (Trucut) for the diagnosis of mediastinal tumors

AimTo determine the contribution of percutaneous biopsy with core cutting needle (Trucut) in the diagnosis of mediastinal tumours. MethodRetrospective review of 56 patients with mediastinal lesions who underwent percutaneous core cutting needle biopsy, oriented but not guided by computer assisted tomography of the thorax, 1999 – 2008. ResultsPercutaneous biopsy with core cutting needle provided adequate material in 49/56, with a total positive sample rate of 88%. In 7/56 (12%) cases the material was insufficient to define the diagnosis. Percutaneous core cutting needle biopsy established a specific histological diagnosis in 88% of the patients: 23/56 (41%) lymphomas; 12/56 (21%) thymomas; 5/56 (3%) thymic carcinomas; 3/56 (2%) small cell carcinoma and 1/56 (0.6%) metastatic adenocarcinoma, metastatic squamous cell carcinoma, neuroendocrine primitive carcinoma, plasmocytoma, teratoma and goiter. All patients underwent thoracic X-ray after the procedure. No complications were found in these patients. ConclusionPercutaneous core cutting needle biopsy (Trucut) oriented but not guided by computer assisted tomography of the thorax is an easy and safe procedure which can provide a precise diagnosis in the majority of mediastinal tumours and can prevent the need for exploratory thoracic surgery in cases which are medically treatable or non-resectable.

A STUDY ON THE OCCURRENCE OF AFLATOXIN IN RAW MILK DUE TO FEEDS

ABSTRACT Milk and milk products are the most important group of food which carries aflatoxin to the people. Therefore, the existence of aflatoxin M1 (AFM1) in milk is a potential risk for public health. AFM1 existence in milk and milk products was found in studies performed in Turkey. In this study, aflatoxin contamination was detected in 48 raw milk and 48 feed samples. Milk and feed samples, in which the positive sample rate was determined as 24%, included different levels of aflatoxin. Altogether, 20 raw milk samples (41.67%) and 15 feed samples (31.25%) contained over the level of legal limits established by the Turkish Food Codex (TFC) and the European Communities (EC) regulation in positive samples. According to these results, the milk and feed samples collected from this area constitute a potential risk for public health. The most effective way of controlling aflatoxin M1 in milk is to reduce the contamination of aflatoxin in raw milk and feed samples. Both the producers and the consumers, as well as the government, have important obligations on this subject.

Skin Exposure to Aliphatic Polyisocyanates in the Auto Body Repair and Refinishing Industry: A Qualitative Assessment

Although respiratory exposures have been the primary concern with isocyanates, skin exposure also can occur and may contribute to sensitization and asthma. Methodologies to assess isocyanate skin exposure in the workplace are limited and skin exposure data scarce. The goals of this study were (i) to evaluate and validate the isocyanate colorimetric indicators against a quantitative assay, (ii) to evaluate the extent of isocyanate surface contamination and skin exposure among auto body shop workers and (iii) to evaluate isocyanate skin exposure determinants. The colorimetric indicators were compared with a high-performance liquid chromatography (HPLC) quantitative assay based on the National Institute for Occupational Safety and Health Method 5525 using paired laboratory sampling. The colorimetric indicators were then used to assess surface contamination and skin exposure to aliphatic isocyanates in 35 auto body shops and 124 workers as part of an epidemiologic study. The positive sample rate was calculated for various surfaces, body parts and tasks. The color intensity of the colorimetric indicators was rated on a scale 0 (yellow color) to 5 (deep red). Side-by-side comparisons of the qualitative method with the quantitative HPLC assay were also performed in the field using paired samples. Laboratory and field evaluation validated use of the colorimetric indicators. The rate of positive surface samples for isocyanates was 46% (n = 145/313). Thirty-four percent (73/216) of samples were positive for unprotected skin and 20% (n = 22/111) for skin under latex gloves. The highest positive rate observed on skin samples was obtained after paint mixing and spraying tasks. The colorimetric indicators were highly specific for isocyanates, but false negatives occurred when compared with the more sensitive HPLC quantitative assay. The presence of surface contamination and the performance of paint-related tasks were the major determinants of isocyanate skin exposure. This study documents extensive surface contamination and skin exposure, including under gloves, to aliphatic polyisocyanates during painting and paint mixing tasks in auto body shop workers. Contaminated surfaces and aerosol deposition during spray painting may both contribute to skin exposure. The colorimetric indicator is a quick, practical and low-cost, but not highly sensitive, industrial hygiene tool to detect isocyanate surface contamination and skin exposures following the use of isocyanate-containing products.

Malaria in Colombia: retrospective glance during the past 40 years

Describe and analyze the structural configuration of malaria in Colombia since 1960 to 2004 where the phenomena of persistence, resurgence and resistance as well as the main determinants associated to these phenomena. A comparative study of the history of malaria and its trend was conducted in Colombia since 1960-2004. Secondary and primary information about the frequency and spatial distribution of malaria was collected. The sub period were identified according to institutional transformation and malaria control strategies as well as the socioeconomic and sociopolitical conjuncture factors in the country. The structural and situational analyses of malaria in Colombia shown a steadily increase in morbidity from an average API 2,19 x 1 000 in 1960-74 to 8,92 by 1994-2004. Since the middle 70's there has been a considerable reduction of mortality. The malaria case relation P. vivax vs. P. falciparum is 3 to 5, respectively. The Annual Positive Sample Rate increased during the same study periods from 3.96% to 29.93%. Unfortunately the Annual Blood Examination Rate-ABER decreased by fewer than 5%, instead of increase to minimum required for detection of malaria. During the National Eradication Malaria Service the malaria decreased steadily by the first five years, unfortunately the disease present resurgence, persistence after the reduction of financial and technical support from international health agencies in the middle seventies. Nowadays, around 85% of the territory, mainly rural areas are endemic for malaria. In spite of the transformation of the health system and different strategies implemented against malaria, it continues being one of the priorities in the public health services of Colombia.

Legionella Pneumonia and Serum Procalcitonin

Procalcitonin is a specific marker of severe bacterial infections with systemic inflammation. Quantitative evaluation of serum procalcitonin was performed in 140 patients with Legionella pneumonia. Positive values (>0.5 ng/mL) were found in 57.1% of the subjects. The positive sample rate was higher in early sera (73.9% in the first week) and decreased progressively. Mean values and the positive sample rate (69.8%) were higher in sera collected in the first 2 weeks of disease. Procalcitonin was positive in 86.7% of legionellosis cases confirmed by culture and mean positive values were significantly higher (P < 0.001) than those of culture-negative subjects. We conclude that procalcitonin can represent a useful prognostic marker for severe suspected Legionella pneumonia in the first 2 weeks of disease.

Transthoracic biopsy with core cutting needle for the diagnosis of mediastinal tumors

OBJECTIVE: To determine the contribution of percutaneous biopsy with core cutting needle in the diagnosis of mediastinal tumors. METHOD: Retrospective review of 22 patients with mediastinal lesions who were submitted to percutaneous core cutting needle biopsy, oriented, but not guided by computer assisted tomography of the thorax, between 1999 and 2002. RESULTS: Percutaneous biopsy with core cutting needle provided adequate material in 18/22 cases, with a total positive sample rate of 82%. In 4/22 cases, the material was insufficient to define the diagnosis (18%). Percutaneous core cutting needle biopsy established a specific histologic diagnosis in 82% of the patients: 8/22 (36%) lymphoma; 5/22 (28%) thymoma; 2/22 (11%) thymic carcinoma; 1/22 (6%) metastatic adenocarcinoma; 1/22 (6%) neuroectodermic primitive tumor; and 1/22 (6%) plasmocytoma. All the patients were submitted to a thoracic X-ray after the biopsy. No complications were found in these patients. CONCLUSION: Percutaneous core cutting needle biopsy oriented, but not guided by computer assisted tomography of the thorax, is an easy and safe procedure which can provide a precise diagnosis in most mediastinal tumors, and can prevent the exploratory thoracic surgery in inoperable or chemotherapy-treated cases.