Cryptosporidium parvum is a leading pathogen in children in developing countries. To investigate whether early postnatal malnutrition leads to heavier C. parvum infections, we assessed intestinal adaptation and parasite load in suckling mice during the first 2 wk of life, analogous to the first postnatal yr in humans. Undernutrition was induced by daily C57BL6J pup separation from lactating dams. Half of the pups were separated daily, for 4 hr on day 4, 8 hr on day 5, and for 12 hr from day 6 until day 14. On day 6, each pup received an oral inoculum of 10 5 to 10 7 parasites in 10-25 μl of PBS. Littermate controls received PBS alone. Stools were assessed from days 8, 11, and 14 for oocyst counts. Mice were killed on day 14, 8 days postinoculation, at the peak of the infection. Ileal and colon segments were obtained for histology, real-time and reverse transcriptase PCR, and immunoassays. Villus and crypt lengths and cross-sectional areas were also measured. Undernourished and nourished mice infected with excysted 10 6 or 10 7 oocysts exhibited the poorest growth outcomes compared with their uninfected controls. Nourished 10 6 -infected mice had comparable weight decrements to uninfected undernourished mice. Body weight and villi were additively affected by malnutrition and cryptosporidiosis. Hyperplastic crypts and heavier inflammatory responses were found in the ilea of infected malnourished mice. Undernourished infected mice exhibited greater oocyst shedding, TNF-α and IFN-γ intestinal levels, and mRNA expression compared to nourished mice infected with either 10 5 or 10 6 oocysts. Taken together, these findings show that Cryptosporidium infection can cause undernutrition and, conversely, that weanling undernutrition intensifies infection and mucosal damage.Cryptosporidiosis, first described by Tyzzer (1907) in the gastric glands of infected mice (Tzipori and Ward, 2002), has emerged as an increasingly recognized public health threat. Cryptosporidium spp. have been identified in watery diarrhea of patients with HIV and other immunocompromised patients and in large human outbreaks of diarrhea in both developed and developing parts of the world (Harp, 2003;Ramirez et al., 2004;Houpt et al., 2005). Furthermore, the long-term impact of cryptosporidial infection has been increasingly recognized in impoverished settings around the world (Checkley et al., 1997;Guerrant, 1997;Checkley et al., 1998 protozoan is adapted to survive and spread in the environment (Dillingham et al., 2002;Karanis et al., 2007).Crowded households with inadequate sanitation further aggravate the likelihood of the infection spreading from person to person (Newman et al., 1999;Caccio and Pozio, 2006). The lack of adequate treatment or prevention for high-risk groups for this chlorine-resistant food-and waterborne protozoan adds to the difficulties controlling cryptosporidial infections (Smith and Corcoran, 2004).Impoverished household environments and water contamination tremendously increase the risk of exposure to waterborne pathogen...

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BackgroundProtease inhibitors (PI's) and reverse transcriptase drugs are important components of highly active antiretroviral therapy (HAART) for treating human acquired immunodeficiency syndrome (AIDS). Long-term clinical therapeutic efficacy and treatment compliance of these agents have been limited by undesirable side-effects, such as diarrhea. This study aims to investigate the effects of selected antiretroviral agents on intestinal histopathology and function in vivo and on cell proliferation and death in vitro.MethodsSelected antiretroviral drugs were given orally over 7 days, to Swiss mice, as follows: 100 mg/kg of nelfinavir (NFV), indinavir (IDV), didanosine (DDI) or 50 mg/kg of zidovudine (AZT). Intestinal permeability measured by lactulose and mannitol assays; net water and electrolyte transport, in perfused intestinal segments; and small intestinal morphology and cell apoptosis were assessed in treated and control mice. In vitro cell proliferation was evaluated using the WST-1 reagent and apoptosis and necrosis by flow cytometry analysis.ResultsNFV, IDV, AZT and DDI caused significant reductions in duodenal and in jejunal villus length (p < 0.05). IDV and AZT increased crypt depth in the duodenum and AZT increased crypt depth in the jejunum. NFV, AZT and DDI significantly decreased ileal crypt depth. All selected antiretroviral drugs significantly increased net water secretion and electrolyte secretion, except for DDI, which did not alter water or chloride secretion. Additionally, only NFV significantly increased mannitol and lactulose absorption. NFV and IDV caused a significant reduction in cell proliferation in vitro at both 24 h and 48 h. DDI and AZT did not alter cell proliferation. There was a significant increase in apoptosis rates in IEC-6 cells after 24 h with 70 ug/mL of NFV (control: 4.7% vs NFV: 22%) while IDV, AZT and DDI did not show any significant changes in apoptosis compared to the control group. In jejunal sections, IDV and NFV significantly increased the number of TUNEL positive cells.ConclusionThe PI's, NFV and IDV, increased cell apoptosis in vivo, water and electrolyte secretion and intestinal permeability and decreased villus length and cell proliferation. NFV was the only drug tested that increased cell apoptosis in vitro. The nucleoside reverse transcriptase inhibitors, AZT and DDI, did not affect cell apoptosis or proliferation. These findings may partly explain the intestinal side-effects associated with PI's.

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Dual-energy X-ray absorptiometry (DXA)-derived bone mineral density (BMD) often fails to predict fragility fractures. Quantitative textural analysis using magnetic resonance imaging (MRI) may potentially yield useful radiomic features to predict fractures. We aimed to investigate the correlation between BMD and texture attributes (TAs) extracted from MRI scans and the interobserver reproducibility of the analysis. METHODS: Forty-nine volunteers underwent lumbar spine 1.5-T MRI and DXA. Three-dimensional (3-D) graylevel co-occurrence matrices were measured from routine sagittal T2 fast spin-echo images using the IBEX software. Twenty-two TAs were extracted from 3-D segmented L3 vertebrae. The estimated concordance coefficient was calculated using linear regression analysis. A Pearson correlation coefficient analysis was performed to evaluate the correlation between BMD and the TAs. Interobserver reproducibility was assessed with the concordance coefficient described by Lin. RESULTS: The results revealed a fair-to-moderate significant correlation between BMD and 13 TAs (r= À 0.20 to 0.39; po0.05). Eight TAs (autocorrelation, energy, homogeneity 1, homogeneity 1.1, maximum probability, sum average, sum variance, and inverse difference normalized) negatively correlated with BMD (r= À 0.20 to À 0.38; po0.05), whereas five TAs (dissimilarity, difference entropy, entropy, sum entropy, and information measure corr 1) positively correlated with BMD (r=0.29-0.39; po0.05). The interobserver agreement was almost perfect for all significant TAs (95% confidence interval, 0.92-1.00; po0.05). CONCLUSION: Specific TAs could be reliably extracted from routine MRI and correlated with BMD. Our results encourage future evaluation of the potential usefulness of quantitative texture measurements from MRI scans for predicting fragility fractures.

The use of routine magnetic resonance imaging (MRI) to potentially assess skeletal fragility has been widely studied in osteoporosis. The aim of this study was to evaluate bone texture attributes (TA) from routine lumbar spine (LS) MRI and their correlation with vertebral fragility fractures (VFF) and bone mineral density (BMD). Sixty-four post-menopausal women were submitted to LS densitometry, total spine radiographs, and routine T2-weighted LS MRI. Twenty-two TA were extracted with the platform IBEX from L3 vertebra. The statistical difference was evaluated using ANOVA and Duncan's post-test. Correlation analyses were performed using Spearman's coefficient. Statistical significance was considered when P<0.05. The results did not show a significant difference in BMD between the women with and without fractures. Two bone TA (cluster tendency and variance) were significantly lower in the fracture group. Cluster tendency with VFF in osteopenia was 1.54±1.37 and in osteoporosis was 1.11±58. Cluster tendency without VFF in osteopenia was 2.23±1.38 and in osteoporosis was 1.88±1.14). Variance with VFF in osteopenia was 1.44±1.37 and in osteoporosis was 1.13±59. Variance without VFF in osteopenia was 2.34±1.38 and in osteoporosis was 1.89±1.14. There was a significant correlation between BMD and cluster prominence (r=0.409), cluster tendency (r=0.345), correlation (r=0.570), entropy (r=0.364), information measure corr1 (r=0.378), inverse variance (r=0.449), sum entropy (r=0.320), variance (r=0.338), sum average (r=-0.274), and sum variance (r=-0.266). Our results demonstrated the potential use of TA extracted from routine MRI as a biomarker to assess osteoporosis and identify the tendency of skeletal fragility vertebral fractures.

Introduction: Osteoarthritis (OA) is a chronic inflammatory degenerative disease, characterized by progressive degeneration of the articular cartilage, affecting mostly the knee joint. The elderly population is the most affected, intensifying the aging process. The concentration of intramuscular adipose tissue in the thigh muscles and knee OA at different ages remains under investigation. Objective: Investigate the cross-sectional area of thigh muscles at different ages with the relationship of the presence of intramuscular fat and knee OA. Methods: 80 participants were paired into 4 groups: Young Osteoarthritis Group and Old Osteoarthritis Group, both sedentary with knee OA diagnosis II or III; Healthy Young Group and Healthy Old Group, both healthy and sedentary. The groups were paired according to gender and body mass index, submitted to physiotherapeutic evaluation, WOMAC questionnaire, knee X-ray and thigh CT scans. Morphometric analysis was performed manually with ITK-SNAP software (version 3.6), by a single evaluator. Statistical analysis used the one-way ANOVA test followed by Bonferroni post-hoc for dependent variables (p≤0.05). Results: Comparison of the cross-sectional area of the rectus femoris, vastus lateralis, semitendinosus, sartorius and gracilis muscles between the groups indicated no significant differences (p>0.05). The study of attenuation for muscle adipose tissue indicated no significant difference in the values of between the OA-Young and Aged-S groups for all the muscles evaluated. Conclusion: Young individuals with knee OA present muscle morphological characteristics similar to those found during the aging process, characterizing early aging of the thigh muscles. Level of Evidence III; Retrospective cross-sectional and observational study.

RESUMO Introdução: A osteoartrite (OA) é uma doença inflamatória crônico-degenerativa, caracterizada pela degeneração progressiva da cartilagem articular, acometendo em maior parte a articulação do joelho. A população idosa é a mais atingida, intensificando o processo de envelhecimento. A concentração de tecido adiposo intramuscular nos músculos da coxa e a OA de joelho em diferentes idades permanece em investigação. Objetivo: Investigar a área de secção transversa dos músculos da coxa em diferentes idades com a relação da presença de gordura intramuscular e OA de joelho. Métodos: 80 participantes foram pareados em 4 grupos: Grupo Osteoartrite Jovem e Grupo Osteoartrite Idoso, ambos sedentários com diagnóstico de OA de joelho II ou III; Grupo Jovem Saudável e Grupo Idoso Saudável, ambos saudáveis e sedentários. Os grupos foram pareados de acordo com sexo e índice de massa corporal, submetidos à avaliação fisioterapêutica, questionário WOMAC, exames de raio-x dos joelhos e tomografia computadorizada da coxa. A análise morfométrica foi realizada manualmente com software ITK-SNAP (versão 3.6), por um único avaliador. Análise estatística utilizou o teste ANOVA one-way seguido pelo post-hoc de Bonferroni, para variáveis dependentes (p≤0,05). Resultados: A comparação da área de secção transversa dos músculos reto femoral, vasto lateral, semitendinoso, sartório e grácil, entre os grupos, não indicou diferenças significativas (p>0,05). O estudo da atenuação para o tecido adiposo muscular não indicou diferença significativa nos valores de entre os grupos OA-Jovem e Idoso-S para todos os músculos avaliados. Conclusão: Indivíduos jovens com OA de joelho apresentam características morfológicas musculares semelhantes às encontradas durante o processo de envelhecimento, caracterizando um envelhecimento precoce dos músculos da coxa.Nível de Evidência III; Estudo retrospectivo transversal e observacional.