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Beef is considered an excellent source of high-quality protein and micronutrients. The high saturated fatty acid (SFA) composition of beef has been associated with cardiovascular diseases; however, this is a controversial issue because at present, no evidence has scientifically proven such an association. Wagyu cattle have been used as an option to generate high-quality fatty acids (FAs) in beef and have been crossed with local beef cattle (Wagyu-Cross). In Mexico, Wagyu-Cross is marketed assuming the same quality as purebred Wagyu meat without scientific support. This study aimed to determine whether the differences in the FA composition of Wagyu-Cross and commercial beef affected lipid metabolism in frequent consumers of beef. The study is a randomized, controlled, double-blinded phase IV clinical trial. Thirty-four volunteers completed treatments in which 120 g ground beef was consumed 3 days per week for 2 weeks. Volunteers were randomized to the "A" (commercial meat) or "B" (Wagyu-Cross meat) groups. The beef fat content was 87% higher, the SFA content was 2.3% lower, and the monounsaturated fatty acid (MUFA) C18:1 n-9 concentrations were higher in Wagyu-Cross beef than in commercial beef. The B group exhibited a significantly larger change from baseline in the serum lipid profile in total cholesterol (TC) (-4.7% versus +6.9%), low-density lipoprotein (LDL) (-4.1% versus +10.0%), nonhigh-density lipoprotein (non-HDL) (-6.1% versus +4.9%), and the ratio of three atherogenic indexes-TC/HDL (-3.5% versus +6.4%), LDL/HDL (-2.8% versus +14.6%), and non-HDL/HDL (-4.7% versus +9.3%)-than the A group. This result confirms that meat FA composition is a key point for redirecting cattle breeding strategies and promotes beef as a healthful protein source. PRACTICAL APPLICATION: Here, we found new evidence based on a clinical trial that beef with a favorable fatty acid composition (i.e., monounsaturated fatty acid and polyunsaturated fatty acid content) is a key factor in improving parameters associated with consumer health. This information will support the design of cattle breeding strategies as an option to promote beef consumption as a healthier protein source and create opportunities for the development of the functional food industry.

Introduction: COVID-19 pandemic affects human health and the global economy. Its evolution is unpredictable, making it hard for governments to provide response actions suited for all populations. Meanwhile, informal street workers carry on with their labor despite contingency measures to sustain their lives. The objective was to conduct a case-control study to become aware of how street vendors' economy is affected during the COVID-19 pandemic. Methodology: During phase 2 of the COVID-19 pandemic in a Mexican suburban city. We interviewed informal street vendors (cases) and formal employees (controls). Results: Before mobility restrictions were in place, population income came 1.5% from formal employment and 23.5% from informal employment (street vendors). Informal employees lived on less than the equivalent of 1.5 Big Macs per day (p

BACKGROUND & AIMS Because inflammatory bowel disease is increasing worldwide and can lead to colitis-associated carcinoma (CAC), new interventions are needed. We have shown that spermine oxidase (SMOX), which generates spermidine (Spd), regulates colitis. Here we determined if Spd treatment reduces colitis and carcinogenesis. METHODS SMOX was quantified in human colitis and associated dysplasia using RT-qPCR and immunohistochemistry. We used wild-type (WT) and Smox–/– C57BL/6 mice treated with dextran sulfate sodium (DSS) or azoxymethane (AOM)-DSS as models of colitis and CAC, respectively. Mice with epithelial-specific deletion of Apc were used as a model of sporadic colon cancer. Animals were supplemented or not with Spd in the drinking water. Colonic polyamines, inflammation, tumorigenesis, transcriptomes, and microbiomes were assessed. RESULTS SMOX mRNA levels were decreased in human ulcerative colitis tissues and inversely correlated with disease activity, and SMOX protein was reduced in colitis-associated dysplasia. DSS colitis and AOM-DSS-induced dysplasia and tumorigenesis were worsened in Smox–/– versus WT mice and improved in both genotypes with Spd. Tumor development caused by Apc deletion was also reduced by Spd. Smox deletion and AOM-DSS treatment were both strongly associated with increased expression of alpha-defensins, which was reduced by Spd. A shift in the microbiome, with reduced abundance of Prevotella and increased Proteobacteria and Deferribacteres, occurred in Smox–/– mice and was reversed with Spd. CONCLUSIONS Loss of SMOX is associated with exacerbated colitis and CAC, increased alpha-defensin expression, and dysbiosis of the microbiome. Spd supplementation reverses these phenotypes, indicating that it has potential as an adjunctive treatment for colitis and chemopreventive for colon carcinogenesis.

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The present study shows the human health risk of Cd, Cu, Hg and Zn by consumption of clams Megapitaria squalida from Northwest Mexico, collected in 2013. The mean concentration for each metal in the soft tissue was: Zn > Cu > Cd > Hg; and mean values of 68.89 ± 37.59—30.36 ± 27.19, 8.77 ± 1.35—6.80 ± 0.36, 4.47 ± 0.21—3.18 ± 0.63 and 0.99 ± 0.81—0.52 ± 0.16 µg/g, respectively. Clam age was significantly negatively correlated (p

Helicobacter pylori-induced gastritis is the strongest risk factor for gastric adenocarcinoma, a malignancy preceded by a series of well-defined histological stages, including metaplasia. One microbial constituent that augments cancer risk is the cag type 4 secretion system (T4SS), which translocates the oncoprotein CagA into host cells. Aberrant stem cell activation is linked to carcinogenesis, and Lrig1 (leucine-rich repeats and Ig-like domains 1) marks a distinct population of progenitor cells. We investigated whether microbial effectors with carcinogenic potential influence Lrig1 progenitor cells ex vivo and via lineage expansion within H. pylori-infected gastric mucosa. Lineage tracing was induced in Lrig1-CreERT2/+;R26R-YFP/+ (Lrig1/YFP) mice that were uninfected or subsequently infected with cag(+) H. pylori or an isogenic cagE(−) mutant (nonfunctional T4SS). In contrast to infection with wild-type (WT) H. pylori for 2 wk, infection for 8 wk resulted in significantly increased inflammation and proliferation in the corpus and antrum compared with uninfected or mice infected with the cagE(−) mutant. WT H. pylori-infected mice harbored significantly higher numbers of Lrig1/YFP epithelial cells that coexpressed UEA1 (surface cell marker). The number of cells coexpressing intrinsic factor (chief cell marker), YFP (lineage marker), and GSII lectin (spasmolytic polypeptide-expressing metaplasia marker) were increased only by WT H. pylori. In human samples, Lrig1 expression was significantly increased in lesions with premalignant potential compared with normal mucosa or nonatrophic gastritis. In conclusion, chronic H. pylori infection stimulates Lrig1-expressing progenitor cells in a cag-dependent manner, and these reprogrammed cells give rise to a full spectrum of differentiated cells.

Background & Aims Metaplasia in the stomach is highly associated with development of intestinal-type gastric cancer. Two types of metaplasias, spasmolytic polypeptide-expressing metaplasia (SPEM) and intestinal metaplasia (IM), are considered precancerous lesions. However, it remains unclear how SPEM and IM are related. Here we investigated a new lineage-specific marker for SPEM cells, aquaporin 5 (AQP5), to assist in the identification of these 2 metaplasias. Methods Drug- or Helicobacter felis (H felis) infection-induced mouse models were used to identify the expression pattern of AQP5 in acute or chronic SPEM. Gene-manipulated mice treated with or without drug were used to investigate how AQP5 expression is regulated in metaplastic lesions. Metaplastic samples from transgenic mice and human gastric cancer patients were evaluated for AQP5 expression. Immunostaining with lineage-specific markers was used to differentiate metaplastic gland characteristics. Results Our results revealed that AQP5 is a novel lineage-specific marker for SPEM cells that are localized at the base of metaplastic glands initially and expand to dominate glands after chronic H felis infection. In addition, AQP5 expression was up-regulated early in chief cell reprogramming and was promoted by interleukin 13. In humans, metaplastic corpus showed highly branched structures with AQP5-positive SPEM. Human SPEM cells strongly expressing AQP5 were present at the bases of incomplete IM glands marked by TROP2 but were absent from complete IM glands. Conclusions AQP5-expressing SPEM cells are present in pyloric metaplasia and TROP2-positive incomplete IM and may be an important component of metaplasia that can predict a higher risk for gastric cancer development., Graphical abstract

Vulpian-Bernhardt syndrome (VBS) is an atypical rare clinical phenotype of amyotrophic lateral sclerosis (ALS) that causes a significant delay in diagnosis, and thus it is important to recognise its clinical and electrophysiological features.Retrospective cross-sectional study. We reviewed the clinical records of patients diagnosed with ALS in the period from January to December 2019. Those meeting criteria for VBS were included so as to describe their frequency as well as their clinical and electrophysiological features.Twenty patients (15.8%) met criteria for VBS; 55% were female; age at onset of symptoms was 46.6 ± 12.9 years; 40% were smokers; median delay in diagnosis was 24 (12-96) months; median time to involvement of the second body segment was 24 (12-132) months, which was lumbosacral in 65%; mean Revised Amyotrophic Lateral Sclerosis Functional Rating Scale score was 27 ± 7 points; 45% met the El Escorial criteria for ALS defined at diagnosis and 58.8% met the Awaji criteria. There were 19 nerve conduction studies and 17 electromyograms, and an abductor digiti minimi-abductor pollicis brevis (ADM/APB) ratio0.6 was found in 63% (split hand).There is a significant delay in the diagnosis of motor neuron diseases in general and more particularly in VBS. Calculating the ADM/APB ratio and applying the Awaji criteria in the electrophysiology study can be a valuable aid to increase diagnostic certainty in this clinical entity.Síndrome de Vulpian-Bernhardt. Frecuencia, características clínicas y electrofisiológicas en un centro de atención de tercer nivel en México.Introducción. El síndrome de Vulpian-Bernhardt (SVB) es un fenotipo clínico atípico e infrecuente de la esclerosis lateral amiotrófica (ELA) que condiciona un importante retraso diagnóstico, por lo que reconocer sus características clínicas y electrofisiológicas tiene relevancia. Materiales y métodos. Estudio retrospectivo y transversal. Se revisaron los expedientes clínicos de pacientes con diagnóstico de ELA en el período de enero de 2017 a diciembre de 2019. Se incluyeron los que cumplían criterios para SVB para describir su frecuencia, características clínicas y electrofisiológicas. Resultados. Veinte pacientes (15,8%) cumplieron los criterios para el SVB; el 55% eran mujeres; la edad de inicio de los síntomas era de 46,6 ± 12,9 años; presentaba tabaquismo el 40%; la mediana de retraso del diagnóstico fue de 24 (12-96) meses; la mediana en afectarse un segundo segmento corporal fue de 24 (12-132) meses, que fue el lumbosacro en el 65%; el promedio en la escala Revised Amyotrophic Lateral Sclerosis Functional Rating Scale fue de 27 ± 7 puntos; el 45% cumplía los criterios de El Escorial para ELA definida en el momento del diagnóstico y el 58,8%, los de Awaji. Se contó con 19 estudios de neuroconducción y 17 electromiogramas, y se encontró una razón abductor digiti minimi-abductor pollicis brevis (APB/ADM) menos de 0,6 en el 63% (mano dividida). Conclusiones. Existe un retraso importante en el diagnóstico de enfermedades de la motoneurona en general y de SVB en particular. Calcular la razón APB/ADM y aplicar los criterios de Awaji en el estudio de electrofisiología puede ser de gran ayuda para aumentar la certeza diagnóstica en esta entidad clínica.

Gastric carcinogenesis is mediated by complex interactions among Helicobacter pylori, host, and environmental factors. Here, we demonstrate that H. pylori augmented gastric injury in INS-GAS mice under iron-deficient conditions. Mechanistically, these phenotypes were not driven by alterations in the gastric microbiota; however, discovery-based and targeted metabolomics revealed that bile acids were significantly altered in H. pylori-infected mice with iron deficiency, with significant upregulation of deoxycholic acid (DCA), a carcinogenic bile acid. The severity of gastric injury was further augmented when H. pylori-infected mice were treated with DCA, and, in vitro, DCA increased translocation of the H. pylori oncoprotein CagA into host cells. Conversely, bile acid sequestration attenuated H. pylori-induced injury under conditions of iron deficiency. To translate these findings to human populations, we evaluated the association between bile acid sequestrant use and gastric cancer risk in a large human cohort. Among 416,885 individuals, a significant dose-dependent reduction in risk was associated with cumulative bile acid sequestrant use. Further, expression of the bile acid receptor transmembrane G protein-coupled bile acid receptor 5 (TGR5) paralleled the severity of carcinogenic lesions in humans. These data demonstrate that increased H. pylori-induced injury within the context of iron deficiency is tightly linked to altered bile acid metabolism, which may promote gastric carcinogenesis.

During phase 2 of the COVID-19 pandemic in a Mexican City, informal street vendors (cases) and formal employees (controls) were interviewed. A total of 82.6% of street vendors preferred to expose themselves to the coronavirus than to stop working, compared with 18.4% of formal employees (adjusted OR = 19.4, 95%CI: 4.6-81.7, p < 0.001). Street vendors had 7 times less fear of dying from coronavirus (adjusted OR = 0.14, 95% CI: 0.03-0.5, p = 0.005) and showed a 16-times greater lack of real concern for the increase in cases in their community than the formal employees (adjusted OR = 0.06, 95% CI: 0.01-0.3, p = 0.002). Street vendors were the group with the poorest adherence to household and work area containment measures that continued to be in contact with others. The corresponding authorities must plan specific strategies that allow street vendors to survive economically, while at the same time, protecting community health.

Introduction: Due to the coronavirus pandemic, identifying the infected individuals has become key to limiting its spread. Virus nucleic acid real-time RT-PCR testing has become the current standard diagnostic method but high demand could lead to shortages. Therefore, we propose a detection strategy using a one-step nested RT-PCR. Methodology: The nucleotide region in the ORF1ab gene that has the greatest differences between the human coronavirus and the bat coronavirus was selected. Primers were designed after that sequence. All diagnostic primers are species-specific since the 3´ end of the sequence differs from that of other species. A primer set also creates a synthetic positive control. Amplified products were seen in a 2.5% agarose gel, as well as in an SYBR Green-Based Real-Time RT-PCR. Results: Amplification was achieved for the positive control and specific regions in both techniques. Conclusions: This new technique is flexible and easy to implement. It does not require a real-time thermocycler and can be interpreted in agarose gels, as well as adapted to quantify the viral genome. It has the advantage that if the coronavirus mutates in one of the key amplification nucleotides, at least one pair can still amplify, thanks to the four diagnostic primers.

INTRODUCTION Factors associated with osteodystrophy in predialysis patients are poorly understood. In the present study, we attempted to evaluate the impact of body composition and hormonal regulatory factors on the bone microstructure in a group of men with chronic kidney disease (CKD) stages 3 and 4. MATERIALS AND METHODS 46 men, aged 50 - 75 years, with previously unrecognized CKD were evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT), and dual-energy X-ray absorptiometry (DXA). HR-pQCT parameters were correlated with estimated glomerular filtration rate (eGFR), age, body mass index (BMI), muscle mass index (MMI), and biochemistry. RESULTS As compared to patients in stage 3 CKD, those with stage 4 CKD showed lower serum 25-hydroxyvitamin D (25(OH)D) and bicarbonate levels, and higher serum fibroblast growth factor 23 (FGF-23) and parathyroid hormone (PTH) levels. They also exhibited lower total, trabecular, and cortical volumetric bone mineral density, lower trabecular bone volume/tissue volume, trabecular number, trabecular and cortical thickness, and increased heterogeneity of the trabecular network. In the whole cohort, cortical bone density and thickness were negatively associated with age, PTH, and FGF-23, and positively with BMI. Trabecular bone parameters were positively associated with MMI and 25(OH)D. After simultaneously adjusting for age and eGFR, BMI, and MMI remained significantly associated with bone microstructural variables. CONCLUSION HR-pQCT showed significant differences in bone microstructure in stage 4 vs. stage 3 CKD patients. Increased BMI, probably due to increased muscle mass, may favorably affect bone architecture in predialysis CKD patients. .

Macrophages are professional immune cells that ingest and kill microbes. In this study, we show that different pathogenic bacteria induce the expression of cystathionine γ-lyase (CTH) in macrophages. This enzyme is involved in a metabolic pathway called the reverse transsulfuration pathway, which leads to the production of numerous metabolites, including cystathionine. Phagocytized bacteria use cystathionine to better survive in macrophages. In addition, the induction of CTH results in dysregulation of the metabolism of polyamines, which in turn dampens the proinflammatory response of macrophages. In conclusion, pathogenic bacteria can evade the host immune response by inducing CTH in macrophages., The reverse transsulfuration pathway is the major route for the metabolism of sulfur-containing amino acids. The role of this metabolic pathway in macrophage response and function is unknown. We show that the enzyme cystathionine γ-lyase (CTH) is induced in macrophages infected with pathogenic bacteria through signaling involving phosphatidylinositol 3-kinase (PI3K)/MTOR and the transcription factor SP1. This results in the synthesis of cystathionine, which facilitates the survival of pathogens within myeloid cells. Our data demonstrate that the expression of CTH leads to defective macrophage activation by (i) dysregulation of polyamine metabolism by depletion of S-adenosylmethionine, resulting in immunosuppressive putrescine accumulation and inhibition of spermidine and spermine synthesis, and (ii) increased histone H3K9, H3K27, and H3K36 di/trimethylation, which is associated with gene expression silencing. Thus, CTH is a pivotal enzyme of the innate immune response that disrupts host defense. The induction of the reverse transsulfuration pathway by bacterial pathogens can be considered an unrecognized mechanism for immune escape.

Mercury and selenium were assessed in Mustelus henlei, which is a carnivorous predatory shark that is important for the coastal communities of the northern Mexican Pacific (NMP). Sixty-two individuals were sampled; muscle and liver were isolated and analyzed by atomic absorption spectrophotometry. The mean Hg concentrations (wet weight) obtained for muscle (0.08 ± 0.10 μg g−1) and liver (0.09 ± 0.26 μg g−1) were below the allowed limits (

The restriction factor BST-2 and the NK cell ligands NTB-A and PVR are among a growing list of membrane proteins found to be downregulated by HIV-1 Vpu. BST-2 antagonism enhances viral release, while NTB-A and PVR downmodulation contributes to NK cell evasion. However, it remains unclear how Vpu can target multiple cellular factors simultaneously. Here we provide evidence that under physiological conditions, BST-2 is preferentially targeted by Vpu over NTB-A and PVR. Specifically, we show that type I IFNs decrease Vpu’s polyfunctionality by upregulating BST-2, thus reducing its capacity to protect HIV-1-infected cells from NK cell responses. This indicates that there is a hierarchy of Vpu substrates upon IFN treatment, revealing that for the virus, targeting BST-2 as part of its resistance to IFN takes precedence over evading NK cell responses. This reveals a potential weakness in HIV-1’s immunoevasion mechanisms that may be exploited therapeutically to harness NK cell responses against HIV-1., The HIV-1 accessory protein Vpu enhances viral release by counteracting the restriction factor BST-2. Furthermore, Vpu promotes NK cell evasion by downmodulating cell surface NTB-A and PVR, known ligands of the NK cell receptors NTB-A and DNAM-1, respectively. While it has been established that Vpu’s transmembrane domain (TMD) is required for the interaction and intracellular sequestration of BST-2, NTB-A, and PVR, it remains unclear how Vpu manages to target these proteins simultaneously. In this study, we show that upon upregulation, BST-2 is preferentially downregulated by Vpu over its other TMD substrates. We found that type I interferon (IFN)-mediated BST-2 upregulation greatly impairs the ability of Vpu to downregulate NTB-A and PVR. Our results suggest that occupation of Vpu by BST-2 affects its ability to downregulate other TMD substrates. Accordingly, knockdown of BST-2 increases Vpu’s potency to downmodulate NTB-A and PVR in the presence of type I IFN treatment. Moreover, we show that expression of human BST-2, but not that of the macaque orthologue, decreases Vpu’s capacity to downregulate NTB-A. Importantly, we show that type I IFNs efficiently sensitize HIV-1-infected cells to NTB-A- and DNAM-1-mediated direct and antibody-dependent NK cell responses. Altogether, our results reveal that type I IFNs decrease Vpu’s polyfunctionality, thus reducing its capacity to protect HIV-1-infected cells from NK cell responses.

Background & Aims Inflammation in the gastrointestinal tract may lead to the development of cancer. Dicarbonyl electrophiles, such as isolevuglandins (isoLGs), are generated from lipid peroxidation during the inflammatory response and form covalent adducts with amine-containing macromolecules. Thus, we sought to determine the role of dicarbonyl electrophiles in inflammation-associated carcinogenesis. Methods The formation of isoLG adducts was analyzed in the gastric tissues of patients infected with Helicobacter pylori from gastritis to precancerous intestinal metaplasia, in human gastric organoids, and in patients with colitis and colitis-associated carcinoma (CAC). The effect on cancer development of a potent scavenger of dicarbonyl electrophiles, 5-ethyl-2-hydroxybenzylamine (EtHOBA), was determined in transgenic FVB/N insulin-gastrin (INS-GAS) mice and Mongolian gerbils as models of H pylori–induced carcinogenesis and in C57BL/6 mice treated with azoxymethane–dextran sulfate sodium as a model of CAC. The effect of EtHOBA on mutations in gastric epithelial cells of H pylori–infected INS-GAS mice was assessed by whole-exome sequencing. Results We show increased isoLG adducts in gastric epithelial cell nuclei in patients with gastritis and intestinal metaplasia and in human gastric organoids infected with H pylori. EtHOBA inhibited gastric carcinoma in infected INS-GAS mice and gerbils and attenuated isoLG adducts, DNA damage, and somatic mutation frequency. Additionally, isoLG adducts were elevated in tissues from patients with colitis, colitis-associated dysplasia, and CAC as well as in dysplastic tumors of C57BL/6 mice treated with azoxymethane–dextran sulfate sodium. In this model, EtHOBA significantly reduced adduct formation, tumorigenesis, and dysplasia severity. Conclusions Dicarbonyl electrophiles represent a link between inflammation and somatic genomic alterations and are thus key targets for cancer chemoprevention.

Helicobacter pylori (H. pylori) is the strongest identified risk factor for gastric cancer, the third most common cause of cancer-related death worldwide. An H. pylori constituent that augments cancer risk is the strain-specific cag pathogenicity island, which encodes a type IV secretion system (T4SS) that translocates a pro-inflammatory and oncogenic protein, CagA, into epithelial cells. However, the majority of persons colonized with CagA+ H. pylori strains do not develop cancer, suggesting that other microbial effectors also have a role in carcinogenesis. Toll-like receptor 9 (TLR9) is an endosome bound, innate immune receptor that detects and responds to hypo-methylated CpG DNA motifs that are most commonly found in microbial genomes. High-expression tlr9 polymorphisms have been linked to the development of premalignant lesions in the stomach. We now demonstrate that levels of H. pylori-mediated TLR9 activation and expression are directly related to gastric cancer risk in human populations. Mechanistically, we show for the first time that the H. pylori cancer-associated cag T4SS is required for TLR9 activation and that H. pylori DNA is actively translocated by the cag T4SS to engage this host receptor. Activation of TLR9 occurs through a contact-dependent mechanism between pathogen and host, and involves transfer of microbial DNA that is both protected as well as exposed during transport. These results indicate that TLR9 activation via the cag island may modify the risk for malignancy within the context of H. pylori infection and provide an important framework for future studies investigating the microbial-epithelial interface in gastric carcinogenesis.

Infection with Helicobacter pylori (H. pylori) leads to inflammatory events that can promote gastric cancer development. Immune cells transition from the circulation into the infected mucosa through the interaction of their receptors and ligands in the endothelial compartment. CD44 expression is increased in advanced gastric lesions. However, the association of this molecule with the progression of these lesions over time has not been investigated. In addition, there is a lack of understanding of the CD44-dependent cellular processes that lead to gastritis, and possibly to gastric cancer. Here we studied H. pylori-positive subjects with gastric lesions that ranged from multifocal atrophic gastritis to dysplasia to determine gene expression changes associated with disease progression over a period of six years. We report that CD44 expression is significantly increased in individuals whose gastric lesions progressed along the gastric precancerous cascade. We also show that CD44−/− mice develop less severe and less extensive H. pylori-induced metaplasia, and show fewer infiltrating Gr1+ cells compared to wild type mice. We present data suggesting that CD44 is associated with disease progression. Mechanisms associated with these effects include induction of interferon gamma responses.

Congenital absence of the cruciate ligaments is a very rare condition, with most reported cases being related to the anterior cruciate ligament (ACL). Posterior cruciate ligament (PCL) congenital abnormalities have been described as almost always being associated with other anomalies. We present a case of a patient with lateral knee pain and subjective instability sensation after a low-energy trauma secondary to a lateral meniscus tear, with absence of the PCL on MRI examination and thickened meniscofemoral ligaments, with anterior and superior insertion at the femur, in the footprint of PCL. The patient had a menisci repair, without PCL reconstruction. At the 6-month follow-up, the patient did not report any instability symptoms during his daily work and sports activities. There are therapeutic implications in distinguishing a chronic PCL tear from an aplasia, so it is important to detect some signs in imaging that may guide to differentiate them, as there could be differences in the course and thickness of meniscofemoral ligaments, besides the absence of the entire PCL. To our knowledge, this is the first case of PCL agenesis with arthroscopic correlation.

Helicobacter pylori is the strongest risk factor for gastric cancer. Initial interactions between H. pylori and its host originate at the microbial-gastric epithelial cell interface, and contact between H. pylori and gastric epithelium activates signaling pathways that drive oncogenesis. One microbial constituent that increases gastric cancer risk is the cag pathogenicity island, which encodes a type IV secretion system that translocates the effector protein, CagA, into host cells. We previously demonstrated that infection of Mongolian gerbils with a carcinogenic cag(+) H. pylori strain, 7.13, recapitulates many features of H. pylori-induced gastric cancer in humans. Therefore, we sought to define gastric proteomic changes induced by H. pylori that are critical for initiation of the gastric carcinogenic cascade. Gastric cell scrapings were harvested from H. pylori-infected and uninfected gerbils for quantitative proteomic analyses using isobaric tags for relative and absolute quantitation (iTRAQ). Quantitative proteomic analysis of samples from two biological replicate experiments quantified a total of 2764 proteins, 166 of which were significantly altered in abundance by H. pylori infection. Pathway mapping identified significantly altered inflammatory and cancer-signaling pathways that included Rab/Ras signaling proteins. Consistent with the iTRAQ results, RABEP2 and G3BP2 were significantly up-regulated in vitro, ex vivo in primary human gastric monolayers, and in vivo in gerbil gastric epithelium following infection with H. pylori strain 7.13 in a cag-dependent manner. Within human stomachs, RABEP2 and G3BP2 expression in gastric epithelium increased in parallel with the severity of premalignant and malignant lesions and was significantly elevated in intestinal metaplasia and dysplasia, as well as gastric adenocarcinoma, compared with gastritis alone. These results indicate that carcinogenic strains of H. pylori induce dramatic and specific changes within the gastric proteome in vivo and that a subset of altered proteins within pathways with oncogenic potential may facilitate the progression of gastric carcinogenesis in humans.

Psychopathology has been closely related with artists. A link between creativity and a tendency to affective disorders has become widely accepted. Several studies have shown that artists suffer disproportionately high rates of mood disorders, particularly manic depression and major depression. The famous twentieth century Spanish artist Joan Miró suffered from depression during the entirety of his life, as was recognized by some authors in private letters. The artist worked using several styles, as well as in ceramics and sculpture. Some of his work reflects the feelings he experienced during the Spanish Civil War and the Second World War. He contributed considerably to the world of art with works such as The Farm as the culminant work of detailism, The Harlequin's Carnival as one of the main expressions of surrealism, the Birth of the World as the precursor of abstract expressionism, or The Dutch Interiors with "mironians" shapes, among others. Whether depression was the inspiration for his work, or his work was the treatment for his depression, will never be clarified. However, he left a great legacy for humanity and his work is admired all over the world.

Shrimp of Farfantepenaeus californiensis (78 groups) and Litopenaeus stylirostris (14 groups) were caught in the northwestern fishing zones in Mexico during the 2014–2015 fishing season (September–February); both shrimp species have high commercial value. Muscle, hepatopancreas and exoskeleton were analyzed to determine their metal contents. For F. californiensis, the highest Cd, Pb and Zn contents were determined in specimens caught off the State of Baja California Sur (BCS) with 22.4 ± 8.9 (hepatopancreas), 2.83 ± 4.63 (muscle), and 748.5 ± 1567 (muscle) µg/g, in the regions off Mulege, Los Cabos and Los Cabos, respectively. For L. stylirostris, the fishing zone of Comundu (BCS) showed higher Cd (12.3 ± 11.5 µg/g), Cu (569.1 ± 646.5 µg/g) and Zn (549.7 ± 400.7 µg/g) contents; all values were determined in the hepatopancreas. Regarding the hazard quotient and total hazard quotient calculated in this study, the consumption of marine shrimp caught off NW Mexico does not represent a risk to human health (both

The conformation of the HIV-1 envelope glycoprotein (Env) substantially impacts antibody recognition and antibody-dependent cellular cytotoxicity (ADCC) responses. In the absence of the CD4 receptor at the cell surface, primary Envs sample a “closed” conformation that occludes CD4-induced (CD4i) epitopes. The virus controls CD4 expression through the actions of Nef and Vpu accessory proteins, thus protecting infected cells from ADCC responses. However, gp120 shed from infected cells can bind to CD4 present on uninfected bystander cells, sensitizing them to ADCC mediated by CD4i antibodies (Abs). Therefore, we hypothesized that these bystander cells could impact the interpretation of ADCC measurements. To investigate this, we evaluated the ability of antibodies to CD4i epitopes and broadly neutralizing Abs (bNAbs) to mediate ADCC measured by five ADCC assays commonly used in the field. Our results indicate that the uninfected bystander cells coated with gp120 are efficiently recognized by the CD4i ligands but not the bNabs. Consequently, the uninfected bystander cells substantially affect in vitro measurements made with ADCC assays that fail to identify responses against infected versus uninfected cells. Moreover, using an mRNA flow technique that detects productively infected cells, we found that the vast majority of HIV-1-infected cells in in vitro cultures or ex vivo samples from HIV-1-infected individuals are CD4 negative and therefore do not expose significant levels of CD4i epitopes. Altogether, our results indicate that ADCC assays unable to differentiate responses against infected versus uninfected cells overestimate responses mediated by CD4i ligands., IMPORTANCE Emerging evidence supports a role for antibody-dependent cellular cytotoxicity (ADCC) in protection against HIV-1 transmission and disease progression. However, there are conflicting reports regarding the ability of nonneutralizing antibodies targeting CD4-inducible (CD4i) Env epitopes to mediate ADCC. Here, we performed a side-by-side comparison of different methods currently being used in the field to measure ADCC responses to HIV-1. We found that assays which are unable to differentiate virus-infected from uninfected cells greatly overestimate ADCC responses mediated by antibodies to CD4i epitopes and underestimate responses mediated by broadly neutralizing antibodies (bNAbs). Our results strongly argue for the use of assays that measure ADCC against HIV-1-infected cells expressing physiologically relevant conformations of Env to evaluate correlates of protection in vaccine trials.

International audience; Despite numerous efforts to identify the molecular and cellular effectors of the adaptive immunity that induce a long-lasting immunity against dengue or Zika virus infection, the specific mechanisms underlying such protective immunity remain largely unknown. One of the major challenges lies in the high level of dengue virus (DENV) seroprevalence in areas where Zika virus (ZIKV) is circulating. In the context of such a pre-existing DENV immunity that can exacerbate ZIKV infection and disease, and given the lack of appropriate treatment for ZIKV infection, there is an urgent need to develop an efficient vaccine against DENV and ZIKV. Notably, whereas several ZIKV vaccine candidates are currently in clinical trials, all these vaccine candidates have been designed to induce neutralizing antibodies as the primary mechanism of immune protection. Given the difficulty to elicit simultaneously high levels of neutralizing antibodies against the different DENV serotypes, and the potential impact of pre-existing subneutralizing antibodies induced upon DENV infection or vaccination on ZIKV infection and disease, additional or alternative strategies to enhance vaccine efficacy, through T cell immunity, are now being considered. In this review, we summarize recent discoveries about cross-reactive B and T cell responses against DENV and ZIKV and propose guidelines for the development of safe and efficient T cell vaccines targeting both viruses.

Background: Development of the intestinal subtype of gastric adenocarcinoma is marked by a progression of histopathologic lesions. Residents of the Andean regions of Colombia are at high risk for gastric cancer. Methods: A cohort of 976 Colombian subjects was followed over 16 years examining effects of Helicobacter pylori eradication and treatment with antioxidants on progression of lesions. We performed methylation analysis of DNA from baseline antral biopsies from 104 subjects for whom follow-up data were available for at least 12 years. Methylation was quantitated for AMPH, CDKN2A, CDH1, EN1, EMX1, NKX6-1, PCDH10, RPRM, RSPO2, SORCS3, ZIC1, and ZNF610 genes, using Pyrosequencing. Results: Levels of DNA methylation were associated with baseline diagnosis for AMPH, EMX1, RPRM, RSPO2, SORCS3, and ZNF610. After adjusting for baseline diagnosis and H. pylori infection, methylation levels of AMPH, PCDH10, RSPO2, and ZNF610 had progression coefficients that increased and P values that decreased over 6, 12, and 16 years. Methylation for SORCS3 was associated with progression at all 3 time points but without the continual strengthening of the effect. Scores for mononuclear leukocytes, polymorphonuclear leukocytes, or intraepithelial lymphocytes were unrelated to progression. Conclusions: Methylation levels of AMPH, PCDH10, RSPO2, SORCS3, and ZNF610 predict progression of gastric lesions independent of the effect of duration of H. pylori infection, baseline diagnosis, gender of the patient, or scores for mononuclear leukocytes, polymorphonuclear leukocytes, or intraepithelial lymphocytes. Impact: DNA methylation levels in AMPH, PCDH10, RSPO2, SORCS3, and ZNF610 may contribute to identification of persons with gastric lesions likely to progress. Cancer Epidemiol Biomarkers Prev; 24(10); 1607–13. ©2015 AACR.

Background Tubular dysfunction is prevalent among kidney transplant patients using calcineurin inhibitors, but our knowledge of the tubular effects of mTOR inhibitors is more limited. Methods 60 kidney transplant outpatients using either the calcineurin inhibitor tacrolimus or the mTOR inhibitor sirolimus were investigated for renal tubular dysfunction. Proximal tubule function was assessed by quantification of albumin and β2-microglobulin, tubular reabsorption of phosphate and fractional excretion of bicarbonate. Distal tubular function was evaluated by water deprivation test and by urinary acidification test using furosemide and fludrocortisone for pH, ammonium and titratable acidity measurements. Results The prevalence of distal renal tubular acidosis (dRTA) was 17% for both treatment groups. 70% of patients treated with sirolimus and 94% using tacrolimus presented with urine concentrating defect (p=0.04). Conclusion Distal RTA and urine concentrating defect were highly prevalent after kidney transplantation both in the sirolimus and tacrolimus treated patients. Acidification test was essential for the appropriate diagnosis of dRTA while dipstick urine specific gravity test was able to detect urine concentrating defect in this population.

The main objective of this study was to evaluate the total mercury content in hepatopancreas and edible muscle of the whiteleg shrimp Litopenaeus vannamei cultured along the NW coast of Mexico, and to evaluate the potential human health risk due to their consumption. Samples were obtained between May and June 2010 in 26 shrimp farms from the three most important shrimp-producing states of NW Mexico, and total Hg was analyzed after reduction with SnCl 2 in a mercury analyzer. The ranges of Hg concentrations of the hepatopancreas were 0.101 ± 0.03–0.184 ± 0.13 μg g −1 in Sonora, 0.077 ± 0.055–0.813 ± 0.363 μg g −1 in Sinaloa and 0.139 ± 0.037–0.791 ± 0.33 μg g −1 in Nayarit. In the muscle, values were from 0.078 ± 0.02 to 0.539 ± 0.09 μg g −1 in Sonora, 0.154 ± 0.03–0.861 ± 0.423 μg g −1 in Sinaloa and 0.121 ± 0.041–1.48 ± 0.44 μg g −1 in Nayarit. Considering the concentrations of Hg in the muscle and the national consumption rate, shrimp farmed in NW Mexico does not represent a risk for human health (HQ

Non-bizarre delusion, defined as a false belief possible although highly unlikely, is the main manifestation of delusional disorders, previously known as paranoia. Based on the predominant delusional themes, 5 main subtypes may be described - erotomanic, grandiose, jealous, persecutory, and somatic. We present here 2 main delusional disorders, the De Clérambault syndrome and the Othello syndrome, and another closely related to the previous ones - Folie à deux. In the De Clérambault syndrome, the main delusional theme is erotomanic type, related to passional delirium where the patient has strong sexual feelings towards another person and has the belief that this other person is deeply in love with him or her. Patients with the Othello syndrome present a delusional disorder of jealous type, a pathological delusion that the partner is unfaithful. In Folie à deux, 2 individuals shared the same psychiatric symptom. However it may be variable, describing variants such as folie imposée or folie simultenée. The risk of aggressive behavior exists in these patients. Knowledge of these syndromes is essential to allow an accurate diagnosis and prompt treatment.

In 1974, Critchley described misoplegia as the phenomenon in which a hemiplegic patient develops a morbid dislike towards the offending immobile limbs. Patients with misoplegia may employ, but more commonly strike their paretic limbs not recognized as self. The pathophysiological mechanism is not well understood. The handful of cases of misoplegia described in the literature, frequently presented a right hemispheric damage. However, patients with chronic spinal cord injury may also present this symptomatology. Not only the modification of behavior by this organic injury, but also the patient reaction to disability and previous personality, may provoke the emergence of misoplegia, probably from other right hemispheric self-unawareness syndromes. No data exists related to treatment option, but we have to remember that the lack of awareness of the deficits in these patients makes the rehabilitation process difficult. Misoplegia is one of the passionate syndromes of the still "not-enough well-known" self-awareness syndromes of the right hemisphere, which shows how brain damage goes much further beyond neurological deficit.

Total mercury (Hg) concentrations were determined by atomic absorption spectrophotometry in muscles and liver of composite samples of Mugil cephalus and M. curema collected during November 2013 and in January, April, and July 2014 from the coastal lagoons Altata-Ensenada del Pabellón (AEP), Ceuta (CEU), and Teacapán-Agua Brava (TAG) of Sinaloa State. The mean Hg contents and information on local consumption were used to assess the possible risk caused by fish ingestion. Mean total mercury levels in the muscles ranged from 0.11 to 0.39 μg/g, while the range for liver was 0.12-3.91 μg/g. The mean Hg content of the liver was significantly (p 0.001) higher than that of the muscles only in samples collected from AEP. Although total Hg levels in the muscles were lower than the official permissible limit, the HQ values for methyl mercury calculated for the younger age classes of one fishing community were1, indicating a possible risk for some fishing communities of the Mexican Pacific coast.

Congenital disorders of lipid metabolism are caused by a wide range of variants of the genes for receptors, apolipoproteins, enzymes, transfer factors, and cellular cholesterol transporters. Clinically most relevant are autosomal dominant familial hypercholesterolemia (FH) and familial combined hyperlipoproteinemia (FCHL). FH has a prevalence of 1:250. It is due to mutations of the low density lipoprotein (LDL) receptor, less often to mutations of the apolipoprotein B (APOB), the proprotein convertase subtilisin/kexin type 9 (PCSK9), or the signal transducing adapter family member 1 (STAP1). FH often leads to early atherosclerosis. Its diagnosis can definitely be made only by molecular genetic testing. The detection of mutations of the LDLR, APOB, or PCSK9 is an indicator for extremely high cardiovascular risk, independently of the concentration of LDL cholesterol. FCHL is also common (1:100) and is seen in about 10% of patients with early myocardial infarction. It is produced by combinations of frequent genetic variants affecting triglycerides and LDL cholesterol. Other monogenic hyperlipoproteinemias (HLP) affect the catabolism of chylomicrons (familial chylomicronemia) or of remnants of triglyceride-rich lipoproteins (type III hyperlipoproteinemia). Multiple hereditary disorders in HDL metabolism - with a broad spectrum of clinical significance - are known. Currently, second generation sequencing methods are used to simultaneously analyze multiple disease-causing genes. This approach cost-neutrally provides additional information such as the genetic risk of atherosclerosis and predisposition to statin intolerance.

Helicobacter pylori incites a futile inflammatory response, which is the key feature of its immunopathogenesis. This leads to the ability of this bacterial pathogen to survive in the stomach and cause peptic ulcers and gastric cancer. Myeloid cells recruited to the gastric mucosa during H. pylori infection have been directly implicated in the modulation of host defense against the bacterium and gastric inflammation. Heme oxygenase-1 (HO-1) is an inducible enzyme that exhibits anti-inflammatory functions. Our aim was to analyze the induction and role of HO-1 in macrophages during H. pylori infection. We now show that phosphorylation of the H. pylori virulence factor cytotoxin-associated gene A (CagA) in macrophages results in expression of hmox-1, the gene encoding HO-1, through p38/NF (erythroid-derived 2)-like 2 signaling. Blocking phagocytosis prevented CagA phosphorylation and HO-1 induction. The expression of HO-1 was also increased in gastric mononuclear cells of human patients and macrophages of mice infected with cagA+ H. pylori strains. Genetic ablation of hmox-1 in H. pylori–infected mice increased histologic gastritis, which was associated with enhanced M1/Th1/Th17 responses, decreased regulatory macrophage (Mreg) response, and reduced H. pylori colonization. Gastric macrophages of H. pylori–infected mice and macrophages infected in vitro with this bacterium showed an M1/Mreg mixed polarization type; deletion of hmox-1 or inhibition of HO-1 in macrophages caused an increased M1 and a decrease of Mreg phenotype. These data highlight a mechanism by which H. pylori impairs the immune response and favors its own survival via activation of macrophage HO-1.

Objective Helicobacter pylori strains that express the oncoprotein CagA augment risk for gastric cancer. However, the precise mechanisms through which cag + strains heighten cancer risk have not been fully delineated and model systems that recapitulate the gastric niche are critical for understanding pathogenesis. Gastroids are three-dimensional organ-like structures that provide unique opportunities to study host- H. pylori interactions in a preclinical model. We used gastroids to inform and direct in vitro studies to define mechanisms through which H. pylori modulates expression of the cancer-associated tight junction protein claudin-7. Design Gastroids were infected by luminal microinjection, and MKN28 gastric epithelial cells were cocultured with H. pylori wild-type cag + strains or isogenic mutants. β-catenin, claudin-7 and snail localisation was determined by immunocytochemistry. Proliferation was assessed using 5-ethynyl-2′-deoxyuridine, and levels of claudin-7 and snail were determined by western blot and flow cytometry. Results Gastroids developed into a self-organising differentiation axis and H. pylori induced mislocalisation of claudin-7 and increased proliferation in a CagA- and β-catenin-dependent manner. In MKN28 cells, H pylori -induced suppression of claudin-7 was regulated by β-catenin and snail. Similarly, snail expression was increased and claudin-7 levels were decreased among H. pylori -infected individuals. Conclusions H. pylori increase proliferation in a strain-specific manner in a novel gastroid system. H. pylori also alter expression and localisation of claudin-7 in gastroids and human epithelial cells, which is mediated by β-catenin and snail activation. These data provide new insights into molecular interactions with carcinogenic potential that occur between H. pylori and epithelial cells within the gastric niche.

Introduction Definitive treatment of symptomatic atheromatous internal carotid artery occlusion remains controversial, as far as in rare cases, late spontaneous recanalization has been seen. Methods We consecutively studied 182 patients (January 2003 to August 2012) with an ischemic stroke in the internal carotid artery territory and diagnosis of atheromatous internal carotid artery occlusion during hospitalization. Findings Seven patients presented a late spontaneous recanalization (>3 months) of the internal carotid artery. We described therapeutic attitude according to usual care in these patients. Conclusions The authors attempt to highlight the unusual condition of recanalization after a symptomatic atheromatous chronic internal carotid artery occlusion. If these patients can be treated similar to patients with asymptomatic carotid pathology, then this needs to be clarified. However, due to the risk of ipsi- and contralateral ischemic strokes, revascularization techniques should be considered in certain cases. More studies are needed to establish the most appropriate therapeutical approach in order to avoid arbitrary treatment of these patients.

A 77-year-old woman with atrial fibrillation (AF) treated with warfarin had a cortical left middle cerebral artery (MCA) stroke (October 2009, international normalized ratio [INR], 1.6) and a cortical left frontal stroke (October 2011, INR, 1.9). Anticoagulation was adjusted. In October 2011, she had a right frontal stroke (INR, 2.3). Acetylsalicylic acid (ASA) was temporally added to the treatment. In June 2013, she had a left occipital stroke (INR, 2.3). Warfarin was changed to rivaroxaban. In August 2013, she had a right occipital stroke. ASA 100 was added to the treatment. On all occasions, repeated neurovascular studies and echocardiography were normal. Diagnoses were cardioembolic stroke. In November 2013, she was admitted because of a left MCA stroke. A complete blood analysis showed the presence of anticardiolipin, anti-b2-glycoprotein antibodies, and lupus anticoagulant. Primary antiphospholipid syndrome (APS) was later confirmed. APS should be considered in young stroke patients, however is not frequent in stroke patients older than 70 years with several cerebrovascular risk factors. The existence of AF in our patient with several embolic strokes made the cardiembolic etiology likely. Uncommon causes of stroke were not considered despite the repetition of the ischemic events. Thus, a wider etiological study should be made in all patients with a recurrent stroke regardless of age, such as a complete blood analysis including immunology study in order to exclude an APS of late onset.

// Jone Garay 1 , M. Blanca Piazuelo 2 , Lizbeth Lopez-Carrillo 3 , Yelda A. Leal 4 , Sumana Majumdar 1 , Li Li 1 , Nataly Cruz-Rodriguez 1, 5, 6 , Silvia J. Serrano-Gomez 1, 5, 6 , Carlos S. Busso 7 , Barbara G. Schneider 2 , Alberto G. Delgado 2 , Luis E. Bravo 8 , Angela M. Crist 9 , Stryder M. Meadows 9 , M. Constanza Camargo 10 , Keith T. Wilson 2, 11 , Pelayo Correa 2 and Jovanny Zabaleta 1, 12 1 Stanley S. Scott Cancer Center, LSUHSC, New Orleans, LA, USA 2 Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA 3 Instituto Nacional de Salud Publica, Cuernavaca, Morelos, Mexico 4 Unidad de Investigacion Medica Yucatan de la Unidad Medica de Alta Especialidad (UMAE) del Instituto Mexicano del Seguro Social (IMSS), Yucatan, Mexico 5 Pontificia Universidad Javeriana, Bogota, Colombia 6 Grupo de Investigacion en Biologia del Cancer, Instituto Nacional de Cancerologia, Bogota, Colombia 7 Department of Otorhinolaryngology, LSUHSC, New Orleans, LA, USA 8 Department of Pathology, Universidad del Valle, Cali, Colombia 9 Department of Cell and Molecular Biology Tulane University, New Orleans LA, USA 10 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA 11 Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA 12 Department of Pediatrics, LSUHSC, New Orleans, LA, USA Correspondence to: Jovanny Zabaleta, email: jzabal@lsuhsc.edu Keywords: precancerous gastric lesions, DMBT1 , H. pylori , inflammation, gastric cancer Received: October 25, 2016 Accepted: March 16, 2017 Published: April 03, 2017 ABSTRACT Helicobacter pylori infection triggers a cascade of inflammatory stages that may lead to the appearance of non-atrophic gastritis, multifocal atrophic, intestinal metaplasia, dysplasia, and cancer. Deleted in malignant brain tumors 1 (DMBT1) belongs to the group of secreted scavenger receptor cysteine-rich proteins and is considered to be involved in host defense by binding to pathogens. Initial studies showed its deletion and loss of expression in a variety of tumors but the role of this gene in tumor development is not completely understood. Here, we examined the role of DMBT1 in gastric precancerous lesions in Caucasian, African American and Hispanic individuals as well as in the development of gastric pathology in a mouse model of H. pylori infection. We found that in 3 different populations, mucosal DMBT1 expression was significantly increased (2.5 fold) in individuals with dysplasia compared to multifocal atrophic gastritis without intestinal metaplasia; the increase was also observed in individuals with advanced gastritis and positive H. pylori infection. In our animal model, H. pylori infection of Dmbt1-/- mice resulted in significantly higher levels of gastritis, more extensive mucous metaplasia and reduced Il33 expression levels in the gastric mucosa compared to H. pylori -infected wild type mice. Our data in the animal model suggest that in response to H. pylori infection DMBT1 may mediate mucosal protection reducing the risk of developing gastric precancerous lesions. However, the increased expression in human gastric precancerous lesions points to a more complex role of DMBT1 in gastric carcinogenesis.

Solute carrier family 7 member 2 (SLC7A2) is an inducible transporter of the semi-essential amino acid L-arginine (L-Arg), which has been implicated in immune responses to pathogens. We assessed the role of SLC7A2 in murine infection with Citrobacter rodentium, an attaching and effacing enteric pathogen that causes colitis. Induction of SLC7A2 was upregulated in colitis tissues, and localized predominantly to colonic epithelial cells. Compared to wild-type mice, Slc7a2 –/–mice infected with C. rodentium had improved survival and decreased weight loss, colon weight, and histologic injury; this was associated with decreased colonic macrophages, dendritic cells, granulocytes, and Th1 and Th17 cells. In infected Slc7a2 –/–mice, there were decreased levels of the proinflammatory cytokines G-CSF, TNF-α, IL-1α, IL-1β, and the chemokines CXCL1, CCL2, CCL3, CCL4, CXCL2, and CCL5. In bone marrow chimeras, the recipient genotype drove the colitis phenotype, indicative of the importance of epithelial, rather than myeloid SLC7A2. Mice lacking Slc7a2 exhibited reduced adherence of C. rodentium to the colonic epithelium and decreased expression of Talin-1, a focal adhesion protein involved in the attachment of the bacterium. The importance of SLC7A2 and Talin-1 in the intimate attachment of C. rodentium and induction of inflammatory response was confirmed in vitro, using conditionally-immortalized young adult mouse colon (YAMC) cells with shRNA knockdown of Slc7a2 or Tln1. Inhibition of L-Arg uptake with the competitive inhibitor, L-lysine (L-Lys), also prevented attachment of C. rodentium and chemokine expression. L-Lys and siRNA knockdown confirmed the role of L-Arg and SLC7A2 in human Caco-2 cells co-cultured with enteropathogenic Escherichia coli. Overexpression of SLC7A2 in human embryonic kidney cells increased bacterial adherence and chemokine expression. Taken together, our data indicate that C. rodentium enhances its own pathogenicity by inducing the expression of SLC7A2 to favor its attachment to the epithelium and thus create its ecological niche., Author Summary Intestinal infections by attaching and effacing (A/E) bacteria widely impact human health, with major social and economic repercussions. Mucosal immunity plays a critical role in determining the outcome of these infections. The amino acid L-arginine regulates inflammatory responses to bacterial pathogens. We studied the role of the L-arginine transporter solute carrier family 7 member 2 (SLC7A2) during infection with the A/E pathogen Citrobacter rodentium. SLC7A2 is induced in colonic epithelial cells during the infection and facilitates the intimate attachment of the bacteria, thus initiating the inflammatory response of the infected mucosa. These data were confirmed in vitro using C. rodentium-infected mouse cells and human colonic epithelial cells infected with enteropathogenic Escherichia coli. Our work describes a mechanism by which A/E bacteria manipulate host response to favor their colonization, thereby positioning SLC7A2 as an unrecognized therapeutic target to limit infection with enterobacteria.

Heart failure (HF) is the leading cause of death worldwide. Efforts to decrease HF mortality rates include a multidisciplinary approach management. Although evidence suggests that this has been an optimal strategy for treating HF, the model remains not widely implanted. The current article explores the rationale behind the formation of a Heart Team in a developing country and its development despite the lack of an allocated budget.

Gastric cancer incidence varies considerably among populations, even those with comparable rates of Helicobacter pylori infection. To test the hypothesis that genetic variation plays a role in gastric disease, we assessed the relationship between genotypes and gastric histopathology in a Colombian study population, using a genotyping array of immune-related single nucleotide polymorphisms (SNPs). Two synonymous SNPs (rs6061243 and rs6587239) were associated with progression of premalignant gastric lesions in a dominant-effects model after correction for multiple comparisons (p = 2.63E-07 and p = 7.97E-07, respectively); effect sizes were β = -0.863 and β = -0.815, respectively, where β is an estimate of effect on histopathology scores, which ranged from 1 (normal) to 5 (dysplasia). In our replication cohort, a second Colombian population, both SNPs were associated with histopathology when additively modeled (β = -0.256, 95 % CI = -0.47, -0.039; and β = -0.239, 95 % CI = -0.45, -0.024), and rs6587239 was significantly associated in a dominant-effects model (β = -0.330, 95 % CI = -0.66, 0.00). Because promoter methylation of GATA5 has previously been associated with gastric cancer, we also tested for the association of methylation status with more advanced histopathology scores in our samples and found a significant relationship (p = 0.001). A multivariate regression model revealed that the effects of both the promoter methylation and the exonic SNPs in GATA5 were independent. A SNP-by-methylation interaction term was also significant. This interaction between GATA5 variants and GATA5 promoter methylation indicates that the association of either factor with gastric disease progression is modified by the other.

To evaluate the long-term effect of cumulative time exposed to795 adults with precancerous gastric lesions were randomised to receive anti-Individuals who were continuously infected withLong-term exposure to

INTRODUCTION: Currently, there is no reliable method to differentiate acute from chronic carotid occlusion. We propose a novel CTA-based method to differentiate acute from chronic carotid occlusions that could potentially aid clinical management of patients. METHODS: We examined 72 patients with 89 spontaneously occluded extracranial internal carotids with CT angiography (CTA). All occlusions were confirmed by another imaging modality and classified as acute (imaging 4 weeks), based on circumstantial clinical and radiological evidence. A neuroradiologist and a neurologist blinded to clinical information determined the site of occlusion on axial sections of CTA. They also looked for (a) hypodensity in the carotid artery (thrombus), (b) contrast within the carotid wall (vasa vasorum), (c) the site of the occluded carotid, and (d) the "carotid ring sign" (defined as presence of a and/or b). RESULTS: Of 89 occluded carotids, 24 were excluded because of insufficient circumstantial evidence to determine timing of occlusion, 4 because of insufficient image quality, and 3 because of subacute timing of occlusion. Among the remaining 45 acute and 13 chronic occlusions, inter-rater agreement (kappa) for the site of proximal occlusion was 0.88, 0.45 for distal occlusion, 0.78 for luminal hypodensity, 0.82 for wall contrast, and 0.90 for carotid ring sign. The carotid ring sign had 88.9% sensitivity, 69.2% specificity, and 84.5% accuracy to diagnose acute occlusion. CONCLUSION: The carotid ring sign helps to differentiate acute from chronic carotid occlusion. If further confirmed, this information may be helpful in studying ischemic symptoms and selecting treatment strategies in patients with carotid occlusions.

The high levels of dengue-virus (DENV) seroprevalence in areas where the Zika virus (ZIKV) is circulating and the cross-reactivity between these two viruses have raised concerns on the risk of increased ZIKV disease severity for patients with a history of previous DENV infections. To determine the role of DENV preimmunity in ZIKV infection, we analyzed the T- and B-cell responses against ZIKV in donors with or without previous DENV infection. Using peripheral blood mononuclear cells (PBMCs) from donors living in an endemic area in Colombia, we have identified, by interferon (IFN)-&gamma, enzyme-linked immunospot (ELISPOT) assay, most of the immunodominant ZIKV T-cell epitopes in the nonstructural (NS) proteins NS1, NS3, and NS5. Analyses of the T- and B-cell responses in the same donors revealed a stronger T-cell response against peptides conserved between DENV and ZIKV, with a higher level of ZIKV-neutralizing antibodies in DENV-immune donors in comparison with DENV-na&iuml, ve donors. Strikingly, the potential for antibody-mediated enhancement of ZIKV infection was reduced in donors with sequential DENV and ZIKV infection in comparison with donors with DENV infection only. Altogether, these data suggest that individuals with DENV immunity present improved immune responses against ZIKV.

The C-terminus of the Helicobacter pylori CagA protein is polymorphic, bearing different EPIYA sequences (EPIYA-A, B, C or D), and one or more CagA multimerization (CM) motifs. The number of EPIYA-C motifs is associated with precancerous lesions and gastric cancer (GC). The relationship between EPIYA, CM motifs and gastric lesions was examined in H. pylori-infected Colombian patients from areas of high and low risk for GC. Genomic DNA was extracted from H. pylori strains cultured from gastric biopsies from 80 adults with dyspeptic symptoms. Sixty-seven (83.8%) of 80 strains were cagA positive. The 3’ region of cagA was sequenced, and EPIYA and CM motifs were identified. CagA proteins contained one (64.2%), two (34.3%) or three EPIYA-C motifs (1.5%), all with Western type CagA-specific sequences. Strains with one EPIYA-C motif were associated with less severe gastric lesions (non-atrophic and multifocal atrophic gastritis), whereas strains with multiple EPIYA-C motifs were associated with more severe lesions (intestinal metaplasia and dysplasia) (p

Background Intravenous recombinant tissular plasminogen activator (rt-PA) is the only approved pharmacological treatment for acute ischaemic stroke. The authors aimed to analyse potential causes of the variable effect on early course and late outcome. Methods and results 136 patients (42% women, 58% men) treated with intravenous rt-PA within 3 h of stroke onset in an acute stroke unit over a 3-year period, were included. Early clinical profiles of evolution at 48 h were divided into clinical improvement (CI) (decrease >4 points in the National Institute of Health Stroke Scale (NIHSS)); clinical worsening (CW) (increase >4 points NIHSS); clinical worsening after initial improvement (CWFI) (variations of >4 points in the NIHSS). Patients with clinical stability (no NIHSS modification or

Ana Maria Martins, MD, PhD, Vânia D’Almeida, MD, Sandra Obikawa Kyosen, MD, Edna Tiemi Takata, MD, Alvimar Goncalves Delgado, MD, PhD, Ângela Maria Barbosa Ferreira Goncalves, MD, Caio Cesar Benetti Filho, MD, Dino Martini Filho, MD, Gilson Biagini, MD, Helena Pimentel, MD, Hugo Abensur, MD, PhD, Humberto Cenci Guimaraes, MD, Jaelson Guilhem Gomes, MD, Jose Sobral Neto, MD, PhD, Luiz Octavio Dias D’Almeida, PhD, Luiz Roberto Carvalho, MD, Maria Beatriz Harouche, MD, Maria Cristina Jacometti Maldonado, MD, Osvaldo J. M. Nascimento, PhD, Paulo Sergio dos Santos Montoril, MD, and Ricardo Villela Bastos, MD

cagA-positive and vacA s1 and m1 genotypes of Helicobacter pylori are associated with an elevated risk of gastric cancer (GC). We determined these genotypes using paraffin-embedded gastric biopsy specimens harvested from infected individuals and compared genotype distributions in two Colombian populations residing in geographic regions with a high and low incidence of GC.DNA from paraffin-embedded gastric biopsies from 107 adults was amplified using primers specific for cagA, for the cag'empty site', for the s and m alleles of vacA, and for H. pylori 16S rRNA.H. pylori infection was detected by molecular assays in 97 (90.7%) biopsies. Complete genotyping of cagA and vacA was achieved in 94 (96.9%) cases. The presence of cagA was detected in 78 of 97 cases (80.4%); when considered separately, cagA and vacA s regions were not significantly associated with a particular geographic area. The vacA m1 allele and s1m1 genotypes were more common in the area of high risk for GC (p = .037 and p = .044, respectively), while the vacA m2 allele and s2m2 genotypes were more prevalent in the low-risk area. The prevalence of the combination of cagA-positive, vacA s1m1 genotypes was 84.3% and 60.5% for high and low risk areas, respectively (p = .011).H. pylori cagA and vacA genotyping from paraffin-embedded gastric biopsies permitted reliable typability and discrimination. The more virulent cagA-positive s1m1 strains, as well as vacA m1 genotype, were more prevalent in high risk than in low risk areas, which may contribute to the difference in GC risk between those two regions.

Abnormal movements are infrequent presentations in acute stroke.1 However, 3 main presentations have been described as being specific to an acute stroke: limb-shaking, hemichorea-hemiballism, and unilateral asterixis.1 We report an abnormal movement that reminds us of a spontaneous limb withdrawal in 3 patients with hyperacute stroke and stroke worsening.