The Extra-Islet Pancreas Supports Autoimmunity in Human Type 1 Diabetes.

In autoimmune Type 1 diabetes (T1D), immune cells progressively infiltrate and destroy the islets of Langerhans - islands of endocrine tissue dispersed throughout the pancreas. However, it is unclear how this process, called 'insulitis', develops and progresses within this organ. Here, using highly multiplexed CO-Detection by indEXing (CODEX) tissue imaging and cadaveric pancreas samples from pre-T1D, T1D, and non-T1D donors, we examine pseudotemporal-spatial patterns of insulitis and exocrine inflammation within large pancreatic tissue sections. We identify four sub-states of insulitis characterized by CD8 + T cells at different stages of activation. We further find that exocrine compartments of pancreatic lobules affected by insulitis have distinct cellularity, suggesting that extra-islet factors may make particular lobules permissive to disease. Finally, we identify "staging areas" - immature tertiary lymphoid structures away from islets where CD8 + T cells appear to assemble before they navigate to islets. Together, these data implicate the extra-islet pancreas in autoimmune insulitis, greatly expanding the boundaries of T1D pathogenesis.

Prognostic importance of DNA from human papillomavirus in patients with oral squamous cell carcinoma.

BACKGROUND: Survival of patients with oral squamous cell carcinoma (OSCC) is generally low, with the likelihood of locoregional recurrence or disease progression (LR/DP). Knowledge of prognostic factors for survival is key to achieving an understanding and increased survival. The present study aimed to identify prognostic factors for patients with OSCC, especially the presence of DNA from human papillomavirus (HPV). MATERIAL AND METHODS: Retrospective cohort study including 119 patients with OSCC treated at the National Cancer Institute in Mexico City (2009-2013). Clinical information was obtained from patient records including LR/DP. Formalin-fixed, paraffin-embedded tissues were obtained and used for detecting DNA from different types of HPV. Potential prognostic factors for Overall Survival (OS) were analyzed using the Cox proportional hazards model. RESULTS: After model adjustment, factors associated with longer OS were a pre-treatment platelet count above 400,000/mm3 (HR=0.09, p=0.026) and response to primary treatment (HR=0.26, p=0.001). HPV DNA was present in 23 (19.3%) of the patients and importantly, type 16 found in 19 of them. Although survival of HPV-positive patients was longer, difference was not significant. However, among patients with LR/DP, HPV positivity was significantly associated with increased survival (HR=0.23, p=0.034). Importantly, survival was significantly different for HPV-positive patients with LR/DP > 6 months (HR=0.20, p=0.002), had higher absolute lymphocyte count at start of treatment (HR=0.50, p=0.028) or had local rescue treatment (HR=0.24, p=0.019). CONCLUSIONS: Although HPV positivity was not associated with a longer OS of OSCC patients, a better prognosis was significantly associated with HPV positivity and recurring or progressing disease, particularly with HPV type 16.

Shielding behavior of artisanal bricks against ionizing photons.

In the work reported in this article, were determined the shielding capabilities of three artisanal bricks used massively in the construction industry in Mexico. The linear attenuation coefficients for photons between 1 keV and 100 GeV are reported; and the half-value layers for energies used in the medical field, show that the three typical artisanal bricks have good shielding capabilities for photons below 50 keV. We compared the effective atomic numbers of one of our bricks against two widely used materials in the construction industry, and our results suggest that the greater the effective atomic number, the less material attenuation capacity. A comparison of the half-value layer of one of our bricks against the half-value layers of two clay bricks with different percentages of fly ash particles published in the literature, suggests that in the region between 0.001 and 2.8 MeV, all the three bricks have practically the same attenuation capacity and that from 2.8 MeV to 100 GeV the clay bricks with different percentages of fly ash particles, need less material to show the same attenuation capacity than our artisanal bricks. Energy Dispersed X-Ray Fluorescence suggests that regardless of the number of constituent elements in a sample, a critical mass per atom is required to have a positive impact on density; and as a consequence, in the capacity of attenuation of the materials. Normalized half-value layers suggest on the other hand, that the uncooked bricks have better shielding capabilities than cooked.

Risk assessment of exposure to mycotoxins (aflatoxins and fumonisins) through corn tortilla intake in Veracruz City (Mexico).

This study aimed to assess aflatoxin and fumonisin intake through corn tortilla consumption in Veracruz city. Between October 2013 and February 2015, a total of 120 corn tortilla samples (2 kg samples, 40 samples per year) were randomly collected. Aflatoxins and fumonisins were quantified by high performance liquid chromatography coupled with a fluorescence detector. A probability density function (PDF) was used for describing corn tortilla intake, body weight of the Veracruz city population, mycotoxin content of corn tortilla samples and estimated mycotoxin daily intake. The Monte Carlo method with 10,000 iterations was employed to assess the population exposure risk. The highest level of total aflatoxins (AFT) was 22.17 µg kg-1, and 526.6 µg kg-1 for fumonisins B1 plus B2, with 85% and 90% of contaminated samples respectively. Up to 69.7 % of the population was estimated to consume a higher aflatoxin dose than that recommended by the JECFA (1 ng kg-1 of body weight per day); it was found that the recommended dose was exceeded to a greater extent in the male population, due to higher consumption of corn. The risk of fumonisin intake was less than 5 % due to the low presence and levels of these toxins in corn tortillas. The results suggest that corn tortilla consumers are at dietary risk caused by AFT contamination; this information should be considered when taking action to protect public health.

Statistical analysis of corn consumption for improved mycotoxin exposure estimates for the population of Veracruz City, Mexico.

Corn consumption was evaluated in the population of Veracruz City, Mexico, through two different dietary intake questionnaires. The selection of 300 sampling locations was completely random. The population was segregated into gender and age categories. A daily consumption questionnaire was used to determine the consumption of corn tortillas and a frequency questionnaire to determine the consumption of other corn products. A book of photographs was used to adjust criteria on the size of the portions of corn products and a probability distribution was built of the weight and content of corn for tortillas. Probability density functions (PDFs) were used to describe the consumption of each corn product. Men and those between 14 and 65 years old have the highest consumption of tortillas. Tortillas, antojitos, tacos and chilaquiles are the products that provide the largest amount of corn to the Veracruz people's diet. Even though these products are nixtamalisated, there is evidence that after a thermo-alkaline process some contaminants such as mycotoxins (like aflatoxin, which is a mutagenic, teratogenic and carcinogenic toxin) could be present in high concentrations. These results highlight the need to characterise the consumption of one of the main foods included in dietary staple in Mexico as a first step for a probabilistic risk assessment.

Retinoblastoma in the adolescent. Unusual clinical and histopathology findings.

CASE REPORT: A 17-year- old male with 2years history of an intraocular mass and progressive visual loss of the left eye. Spontaneous sclera rupture occurred during enucleation. Microscopic evaluation with H-E, PAS and immunohistochemistry (NSE, GAFP, SYN, CD99) revealed a small blue round cell malignant neoplasm with extensive necrosis and apoptosis. The optic nerve, ciliary body, choroid, anterior chamber, and sclera were infiltrated. SYN was positive and CD99 was negative in neoplastic cells, consistent with a poorly differentiated retinoblastoma. DISCUSSION: Retinoblastoma is the most frequent primary intraocular malignant tumour in childhood, but occasionally older patients can be affected. Immunohistochemistry is mandatory in poorly differentiated retinoblastomas.

Concrete enclosure for shielding a neutron source.

In the aim to design a shielding for a 0.185 TBq (239)PuBe isotopic neutron source several Monte Carlo calculations were carried out using MCNP5 code. First, a point-like source was modeled in vacuum and the neutron spectrum and ambient dose equivalent were calculated at several distances ranging from 5 cm up to 150 cm, these calculations were repeated modeling a real source, including air, and a 1×1×1 m(3) enclosure with 5, 15, 20, 25, 30, 50 and 80 cm-thick Portland type concrete walls. At all the points located inside the enclosure neutron spectra from 10(-8) up to 0.5 MeV were the same regardless the distance from the source showing the room-return effect in the enclosure, for energies larger than 0.5 MeV neutron spectra are diminished as the distance increases. Outside the enclosure it was noticed that neutron spectra becomes "softer" as the concrete thickness increases due to reduction of mean neutron energy. With the ambient dose values the attenuation curve in terms of concrete thickness was calculated.

Spontaneous orbiting of two spheres levitated in a vibrated liquid.

In the absence of gravity, particles can form a suspension in a liquid irrespective of the difference in density between the solid and the liquid. If such a suspension is subjected to vibration, there is relative motion between the particles and the fluid which can lead to self-organization and pattern formation. Here, we describe experiments carried out to investigate the behavior of two identical spheres suspended magnetically in a fluid, mimicking weightless conditions. Under vibration, the spheres mutually attract and, for sufficiently large vibration amplitudes, the spheres are observed to spontaneously orbit each other. The collapse of the experimental data onto a single curve indicates that the instability occurs at a critical value of the streaming Reynolds number. Simulations reproduce the observed behavior qualitatively and quantitatively, and are used to identify the features of the flow that are responsible for this instability.

Recombinant small ruminant lentivirus subtype B1 in goats and sheep of imported breeds in Mexico.

Nucleotide sequences of small ruminant lentiviruses (SRLVs) were determined in sheep and goats, including progeny of imported animals, on a farm in Mexico. On the basis of gag-pol, pol, env and LTR sequences, SRLVs were assigned to the B1 subgroup, which comprises caprine arthritis-encephalitis virus (CAEV)-like prototype sequences mainly from goats. In comparison with CAEV-like env sequences of American and French origin, two putative recombination events were identified within the V3-V4 and V4-V5 regions of the env gene of a full length SRLV sequence (FESC-752) derived from a goat on the farm.

Partition instability in water-immersed granular systems.

It is well known that a system of grains, vibrated vertically in a cell divided into linked columns, may spontaneously move into just one of the columns due to the inelastic nature of their collisions. Here we study the behavior of a water-immersed system of spherical barium titanate particles in a rectangular cell which is divided into two columns, linked by two connecting holes, one at the top and one at the bottom of the cell. Under vibration the grains spontaneously move into just one of the columns via a gradual transfer of grains through the connecting hole at the base of the cell. We have developed numerical simulations that are able to reproduce this behavior and provide detailed information on the instability mechanism. We use this knowledge to propose a simple analytical model for this fluid-driven partition instability based on two coupled granular beds vibrated within an incompressible fluid.

Instabilities in vertically vibrated fluid-grain systems.

When a bed of fluid-immersed fine grains is exposed to vertical vibration a wealth of phenomena may be observed. At low frequencies a horizontal bed geometry is generally unstable and the bed breaks spatial symmetry, acquiring a tilt. At the same time it undergoes asymmetric granular convection. Fine binary mixtures may separate completely into layers or patterns of stripes. The separated regions may exhibit instabilities in which they undergo wave-like motion or exhibit quasi-periodic oscillations. We briefly review these and a number of related behaviours, identifying the physical mechanisms behind each. Finally, we discuss the magneto-vibratory separation of binary mixtures which results from exposing each component to a different effective gravity and describe the influence of a background fluid on this process.

Salivary gland myoephitheliomas: cytological, histological, immunohistochemical and electromicroscopical studies of four cases

Se presentan los resultados multidisciplinarios de cuatro casos de mioepiteliomas de glándula salival diagnosticados por biopsia por aspiración con aguja fina y resecados posteriormente. Histológicamente dos casos fueron benignos y dos malignos. Los extendidos celulares de las variedades benignas contenían una población uniforme de células discretamente alargados con citoplasma bipolar y membranas celulares conspicuas. El núcleo fue pequeño y oval con cromatina homogénea. Las células se disponían en grupos y nidos sobre un fondo proteináceo. Se observaron células aisladas adyacentes que presentaban citoplasma eosinófilo, granular y claro con núcleo central, redondo e hipercromático. En uno de los extendidos se observó numerosos capilares con células endoteliales prominentes y fondo con matrix condroide. Dos casos presentaron cambios citológicamente malignos con un fondo necrohemorrágico, pleomorfismo, nucléolo prominente, hipercromatismo y mitosis atípicas ocasionales. Las reacciones de inmunohistoquímica demostraron positividad para proteína S-100 y vimentina y focalmente para citoqueratina. Los hallazgos de la microscopia electrónica correspondieron a células mioepiteliales.

Hepatic carcinoma with spleen metastasis in a California sea lion from the Gulf of California.

A primary hepatic carcinoma with a neuroendocrine pattern was detected in an adult female California sea lion (Zalophus californianus) found dead on Granito Island in the Gulf of California (Mexico) in January 1996. At necropsy, several light yellow nodules of different sizes were observed on the entire surface of the liver and spleen. Microscopic examination of these nodules using routine haematoxylin-eosin stain, revealed cubic, polyhedral and pleomorphic cells with three to four bizarre mitotic figures per field (40X). An immunohistochemistry test revealed a positive reaction of indirect immunoperoxide to cytokeratin (CK2). This is the first known case of a primary hepatic carcinoma in free-ranging California sea lions from Mexican waters.

[Atypical biological behavior of alveolar rhabdomyosarcoma in five patients]. / Comportamiento biológico atípico del rabdomiosarcoma alveolar en cinco pacientes.

Five cases of alveolar rhabdomyosarcoma with atypical clinical features are reported. Three patients showed lymphadenopathy as the first clinical manifestation, mimicking a lymphoma or a non identified primary tumor with lymph node metastases. One patient presented systemic neoplastic disease and two had the primary tumor in atypical locations, such as the mediastinum and retroperitoneum. All patients died and in four of them an autopsy was performed. The histological diagnosis was confirmed by immunohistochemical studies on four cases. The alveolar rhabdomyosarcoma has a poor prognosis and can have a variable clinical presentation and morphology, simulating lymphomas, leukemias and systemic metastatic disease with an unknown primary neoplasm, such as in the cases here in reported.

Human amebic liver abscess: expression of intercellular adhesion molecules 1 and 2 and of von Willebrand factor in endothelial cells.

Liver invasion by amebas with production of amebic liver abscess (ALA) is the most common extraintestinal lesion produced by the protozoan parasite Entamoeba histolytica. This hepatic damage is characterized by the presence of extensive tissue necrosis. However, little is known about the parasite and host factors involved in the process of tissue damage. During the early establishment of amebas in the liver parenchyma as well as during the extension of the tissue necrosis, parasites interact with sinusoidal endothelial cells. As a consequence of ameba-endothelial cell interactions, the latter can be activated and express proinflammatory factors that could be related to tissue destruction. We studied by immunohistochemistry the localization of antigenic molecules of E. histolytica trophozoites and of molecules such as intercellular adhesion molecule 1 (ICAM-1), ICAM-2, and von willebrand factor in activated endothelial cells of human ALA, which could be related to the pathophysiological mechanisms of tissue destruction in amebiasis.

A case report and review: the gross, histological and immunohistochemical characteristics of a carcinoma of ectopic thyroid in a dog.

Neoplasms of the canine thyroid gland represent 5-10% of heart base masses (Capen, 1978). Ectopic thyroid tissue is detected most commonly in the thorax, with 23-80% of all dogs having ectopic tissue at the base of the heart (Leav et al., 1976; Walsh & Diters, 1984). We describe here the gross and microscopic features of a rare ectopic thyroid carcinoma in a dog and the results of an immunohistochemical study of the tumour.

[Third case of human hepatic capillariasis in Mexico]. / Tercer caso de capilariasis hepática humana en México.

A case of hepatic capillariasis in a 54-year-old woman confined to a mental institution is reported. The patient was transferred to the Hospital General de México for terminal care of a breast cancer; she died 12 days after admission. Hepatomegaly was observed clinically and numerous Capillaria hepatica eggs were found at autopsy. The laboratory examinations did not show eosinophilia or other abnormalities. Twenty-six cases of human hepatic capillariasis have been recorded in the world literature. This is the third case reported in Mexico: the previous two in children. Since the patient had a psychiatric condition she may have had aberrant alimentary habits. The features of C hepatica eggs stained with Jone's silver methenamine, which allows the demonstration of an internal multilayered sheath and an external layer endowed with multiple radiated canaliculi, are described in this patient.

Biochemical epidemiology of gallbladder cancer.

To evaluate the a priori hypotheses that an increased level of glyco and tauro lithocholic acid, perhaps because of a decreased capacity for hepatic sulfation, contributed to the biochemical epidemiology of gallbladder cancer, a case-control study was undertaken at four hospitals in La Paz, Bolivia, and at one hospital in Mexico City, Mexico. Eighty-four cases with newly diagnosed histologically confirmed gallbladder cancer were compared with 264 controls with cholelithiasis or choledocholithiasis in the absence of cancer and with 126 controls with normal biliary tracts. All study subjects were undergoing abdominal surgery. Interview data were collected for all study subjects, as well as blood, bile, and gallstone specimens when feasible. Sera were analyzed for carcinoembryonic antigen, cholesterol concentration, and total bile acids. Bile specimens were analyzed for carcinoembryonic antigen; and for concentration of bile salts; cholesterol; phospholipids; and the glycine and taurine conjugates of cholic, ursodeoxycholic, chenodeoxycholic, deoxycholic, and lithocholates; sulfoglycolithocholate; and sulfotaurolithocholate. Gallstone specimens were analyzed for the percentage of cholesterol content, the percentage of calcium bilirubinate content, and the percentage of calcium carbonate content. Serum bile acids were increased in cases versus the two control groups (median 11.7 nmol/mL vs. 9.3 nmol/mL for stone controls and 8.2 nmol/L for nonstone controls, P < or = .02 for each pairwise comparison). Biliary bile acids were markedly decreased in the cases (median 3.98 micromol/mL vs. 33.09 micromol/mL, and 154.0 micromol/L, respectively, P < or = .0001 for each comparison), even after excluding those with a serum bilirubin higher than 2.0 mg/dL. Bile cholesterol was lower for the cases as well (median 1.70 micromol/mL vs. 4.90 micromol/mL, and 16.81 micromol/ mL, respectively, P < or = .02), as was the concentration of bile phospholipids (median 2.97 micromol/mL vs. 6.26 micromol/mL, and 52.69 micromol/mL, P = .1 and .0004, respectively). Contrary to our a priori hypothesis, there was no difference between the cases and either control group in their bile concentrations of lithocholate, the proportion of bile acids which were sulfated, or the concentration of nonsulfated lithocholate. However, the cases had a higher concentration of ursodeoxycholate (UDC) (P < .004 for both control groups), especially glycoursodeoxycholate (P < .001 for both control groups). A previously published suggestion that gallstone size differed between cases and controls was not confirmed. In conclusion, cases with gallbladder cancer differed from controls with stones and from controls with normal biliary tracts in their serum and bile biochemistries. These findings may be a reflection of the disease process, or may provide useful clues to its pathogenesis.