Tumour-stroma ratio to predict pathological response to neo-adjuvant treatment in rectal cancer.

INTRODUCTION: Management of rectal cancer has advanced, with an increasing use of neoadjuvant chemoradiotherapy (nCRT). This opens options for organ preserving treatment for those with a major response to nCRT. However, the degree of clinical response, based on MRI and post-treatment biopsies, only poorly matches the degree of actual pathological response. In order to select patients with major pathological response without surgical resection, it is of importance to define tumour markers predicting the degree of pathological response to nCRT. The intra-tumoural tumour-stroma ratio (TSR) might be this marker. METHODS: TSR in pre-treatment biopsies was estimated according to the method described by van Pelt et al. The degree of pathological response was assessed on the tumour resection according to tumour regression grading (TRG) by Mandard. The primary endpoint of this study was the difference in pathological response to nCRT between TSR-high and TSR-low groups. RESULTS: We found that 26.2% of patients with major response was classified as TSR-high, while 73.8% of patients were classified as TSR-low. A high TSR in pre-treatment biopsies was associated with a lower chance of major-response to nCRT (OR = 0.37, 95%CI; 0.19-0.73), p = 0.004), independent of tumour stage and time between nCRT and surgery. CONCLUSION: In rectal cancer, TSR in pre-treatment biopsies predicts pathologic response to nCRT, with a high TSR bringing twice the risk of poor to no response compared to low TSR. In future, assessment of TSR may fulfil a role in a therapeutic algorithm identifying patients who will or will not respond to nCRT prior to treatment initiation.

Damage control interventional radiology (DCIR) in prompt and rapid endovascular strategies in trauma occasions (PRESTO): A new paradigm.

This article proposes an innovative concept of interventional radiology for hemodynamically unstable trauma patients. Damage control interventional radiology (DCIR) is an aggressive and time-conscious algorithm that prioritizes saving life of the hemorrhaging patient in extremis which conventional emergency interventional radiology (CEIR) cannot efficiently do. Briefly, DCIR aims to save life while CEIR aims to control bleeding with a constant concern to time-awareness. This article also presents the concept of "Prompt and Rapid Endovascular Strategies in Traumatic Occasions" (PRESTO) that entirely oversees and manages trauma patients from arrival to the trauma bay until initial completion of hemostasis with endovascular techniques. PRESTO's "Start soon and finish sooner" relies on the earlier activation of interventional radiology team but also emphasizes on a rapid completion of hemostasis in which DCIR has been specifically tailored. Both DCIR and PRESTO expand the role of IR and represent a paradigm shift in the realm of trauma care.

Correlation between carotid bifurcation calcium burden on non-enhanced CT and percentage stenosis, as confirmed by digital subtraction angiography.

OBJECTIVES: Previous evidence supports a direct relationship between the calcium burden (volume) on post-contrast CT with the percent internal carotid artery (ICA) stenosis at the carotid bifurcation. We sought to further investigate this relationship by comparing non-enhanced CT (NECT) and digital subtraction angiography (DSA). METHODS: 50 patients (aged 41-82 years) were retrospectively identified who had undergone cervical NECT and DSA. A 64-multidetector array CT (MDCT) scanner was utilised and the images reviewed using preset window widths/levels (30/300) optimised to calcium, with the volumes measured via three-dimensional reconstructive software. Stenosis measurements were performed on DSA and luminal diameter stenoses >40% were considered "significant". Volume thresholds of 0.01, 0.03, 0.06, 0.09 and 0.12 cm(3) were utilised and Pearson'S correlation coefficient (r) was calculated to correlate the calcium volume with percent stenosis. RESULTS: Of 100 carotid bifurcations, 88 were available and of these 7 were significantly stenotic. The NECT calcium volume moderately correlated with percent stenosis on DSA r=0.53 (p<0.01). A moderate-strong correlation was found between the square root of calcium volume on NECT with percent stenosis on DSA (r=0.60, p<0.01). Via a receiver operating characteristic curve, 0.06 cm(3) was determined to be the best threshold (sensitivity 100%, specificity 90.1%, negative predictive value 100% and positive predictive value 46.7%) for detecting significant stenoses. CONCLUSION: This preliminary investigation confirms a correlation between carotid bifurcation calcium volume and percent ICA stenosis and is promising for the optimal threshold for stenosis detection. Future studies could utilise calcium volumes to create a "score" that could predict high grade stenosis.

Not the typical Tornwaldt's cyst this time? A nasopharyngeal cyst associated with canalis basilaris medianus.

We report a patient with a cystic structure in the nasopharynx mimicking a Tornwaldt's cyst, which was felt to represent a different entity owing to the lack of the distinct features of a typical Tornwaldt's cyst. It was associated with a bony cleft in the basiocciput that was considered to be a canalis basilaris medianus (CBM), thought to represent an embryological vestige of the cephalic end of the notochord along its course within the basiocciput.

Is food insecurity related to overweight and obesity in children and adolescents? A summary of studies, 1995-2009.

In the USA, several nutrition-related issues confront the normal growth, maturation and development of children and adolescents including obesity and food insecurity. The purpose of this paper is to provide a review of the concept of food insecurity and a summary of studies that have examined the association between food insecurity and overweight/obesity in children and adolescents. Besides the initial case report, we review 21 studies (16 cross-sectional and five prospective studies) that have been published on this topic as of December 2009. As there is limited literature in this area, we review studies that sample children and adolescents in the USA. The results are mixed with positive, negative and null associations. The reasons for the mixed results are difficult to disentangle. Among earlier studies, small samples hampered definitive conclusions. More recent studies with larger samples have overcome these limitations and tend to find no associations between these constructs. Nonetheless, all of the studies to date have shown that food insecurity and overweight co-exist - that is, even though there may not be statistically significant differences in overweight between food-insecure and food-secure children, the prevalence of overweight remains relatively high in food-insecure children.

Linking psychosocial stressors and childhood obesity.

Research has established a wide array of genetic and environmental factors that are associated with childhood obesity. The focus of this review is on recent work that has established the relationship between one set of environmental factors, stressors and childhood obesity. These stressors are particularly prevalent for low-income children, a demographic group that has high rates of obesity in the USA and other developed countries. In this review, we begin by summarizing the psychosocial stressors faced by children followed by health outcomes associated with exposure to these stressors documented in the literature. We then summarize 11 articles which examined the connection between psychosocial stressors in the household and obesity and eight articles which examined the connection between individual psychosocial stressors and obesity. Policy recommendations emerging from this research include recognizing reductions in childhood obesity as a potential added benefit of social safety net programmes that reduce financial stress among families. In addition, policies and programmes geared towards childhood obesity prevention should focus on helping children build resources and capacities to teach them how to cope effectively with stressor exposure. We conclude with suggestions for future research.

MR imaging of Vogt-Koyanagi-Harada syndrome with leptomeningeal enhancement.

We describe a 28-year-old man with presumed VKH syndrome, whose presenting symptoms were bilateral impaired vision and headaches. Orbital MR imaging findings included bilateral choroidal and retrobulbar contrast enhancement, while brain findings included white matter abnormalities on FLAIR and leptomeningeal enhancement. Pachymeningeal enhancement has been described previously; herein, we report a patient with VKH syndrome presenting solely with leptomeningeal enhancement. Thus, MR imaging may detect early CNS involvement by VKH disease before the onset of neurologic symptoms.

Acute hepatic encephalopathy: diffusion-weighted and fluid-attenuated inversion recovery findings, and correlation with plasma ammonia level and clinical outcome.

BACKGROUND AND PURPOSE: In acute hepatic encephalopathy, MR imaging abnormalities have been described in the PVWM, thalami, and corticospinal tracts. We sought to determine characteristic regions of involvement on FLAIR and DWI, to evaluate their reversibility, and to correlate MR imaging extent with clinical severity. MATERIALS AND METHODS: Twenty patients who presented clinically with acute hepatic encephalopathy and MR imaging <21 days after symptom onset were reviewed retrospectively. Two neuroradiologists recorded involved regions on FLAIR and DWI in each, measured ADC values in affected regions and NAWM, and scored the MR imaging severity/extent. The initial severity (West Haven grade), follow-up clinical severity (degree of improvement), and maximal PAL within ±8 days of MR imaging were recorded and correlated with the MR imaging severity. RESULTS: On FLAIR and DWI respectively, there were abnormalities in the thalami (85%, 70%), PLIC (75%, 80%), PVWM (80%, 85%), and DBS (70%, 35%) and diffuse cortical involvement (30%, 25%). There were relatively strong significant (P < .005) correlations of FLAIR (r = 0.680, P = .001) and DWI severity (r = 0.690, P = .001) with PAL, and of PAL with the clinical outcome (r = 0.691, P = .001). Both FLAIR (r = 0.592, P = .006) and DWI (r = 0.487, P = .029) severity correlated moderately with the clinical outcome but were not significant at the P < .005 level after Bonferroni correction. CONCLUSIONS: Patients with acute hepatic encephalopathy may exhibit characteristic regions of involvement on FLAIR with DWI findings that can be reversible. The MR imaging extent on FLAIR and DWI strongly correlates with the maximal PAL, and PAL correlates well with the clinical outcome. Diffuse cortical involvement has a higher potential for neurologic sequelae but can be reversible.

Confirmation of T1-bright vein of Galen aneurysm spontaneous thrombosis by subtraction magnetic resonance venography: a case report.

Spontaneous thrombosis of a vein of Galen aneurysmal malformation (VOGM) is rare. We describe a 2-month-old patient with a patent VOGM and hydrocephalus, also confirmed patent at 6 months, but with subsequent lack of filling on preembolization catheter digital subtraction angiography (DSA) at 9 months' age. Due to the presence of T1- and T2-bright signal, noncontrast T1-weighted images (T1WI), T2-weighted images (T2WI), two-dimensional (2D) time-of-flight (TOF) magnetic resonance venography (MRV), and postcontrast T1WI were ambiguous for patency. However, subtracting the pre- from the postcontrast MRV images confirmed closure compared to subtracted images at 6 months' age. The factors contributing to thrombosis were likely a combination of a disproportionately small straight sinus, ventriculostomy, and contrast medium from DSA.

Syndrome of megalencephaly, polydactyly, and polymicrogyria lacking frank hydrocephalus, with associated MR imaging findings.

Megalencephaly, polymicrogyria, polydactyly, and hydrocephalus (MPPH) syndrome has been recently recognized and is very rare. Each case reported so far has demonstrated hydrocephalus to varying degrees. We report an infant with MPPH syndrome, but lacking frank hydrocephalus. The additional finding of an abnormally elongated pituitary infundibulum has not been described in this syndrome and, along with the presence of a regressing cystic cavum septum pellucidum, suggests that chronic underlying hydrocephalus may have been present.

Protection against simian immunodeficiency virus vaginal challenge by using Sabin poliovirus vectors.

Here we provide the first report of protection against a vaginal challenge with a highly virulent simian immunodeficiency virus (SIV) by using a vaccine vector. New poliovirus vectors based on Sabin 1 and 2 vaccine strain viruses were constructed, and these vectors were used to generate a series of new viruses containing SIV gag, pol, env, nef, and tat in overlapping fragments. Two cocktails of 20 transgenic polioviruses (SabRV1-SIV and SabRV2-SIV) were inoculated into seven cynomolgus macaques. All monkeys produced substantial anti-SIV serum and mucosal antibody responses. SIV-specific cytotoxic T-lymphocyte responses were detected in three of seven monkeys after vaccination. All 7 vaccinated macaques, as well as 12 control macaques, were challenged vaginally with pathogenic SIVmac251. Strikingly, four of the seven vaccinated animals exhibited substantial protection against the vaginal SIV challenge. All 12 control monkeys became SIV positive. In two of the seven SabRV-SIV-vaccinated monkeys we found no virological evidence of infection following challenge, indicating that these two monkeys were completely protected. Two additional SabRV-SIV-vaccinated monkeys exhibited a pronounced reduction in postacute viremia to <10(3) copies/ml, suggesting that the vaccine elicited an effective cellular immune response. Three of six control animals developed clinical AIDS by 48 weeks postchallenge. In contrast, all seven vaccinated monkeys remained healthy as judged by all clinical parameters. These results demonstrate the efficacy of SabRV as a potential human vaccine vector, and they show that the use of a vaccine vector cocktail expressing an array of defined antigenic sequences can be an effective vaccination strategy in an outbred population.

The transition to high school for academically promising, urban, low-income African American youth.

In nine urban Ohio school systems, low-income minority students identified as academically promising in sixth grade are eligible to participate in an intervention program. In the present study, twenty-two African American students in the program were asked to provide their perceptions of the transition to ninth grade. Specifically, the role of motivating factors, peers, school, teachers, parents, and neighborhood were examined. These students faced similar stressors, yet some were more able to achieve academic success. Results highlight the salience of mothers, the challenges of the ninth-grade curriculum, and adjustment to a bigger, more complex school environment for high and low performers. The implications for improving cooperation between school and family are discussed.

Bystander sensitization to activation-induced cell death as a mechanism of virus-induced immune suppression.

Viral infections which induce strong T-cell responses are often characterized by a period of transient immunodeficiency associated with the failure of host T cells to proliferate in response to mitogens or to mount memory recall responses to other antigens. During acute infections, most of the activated, proliferating virus-specific T cells are sensitized to undergo apoptosis on strong T-cell receptor (TCR) stimulation, but it has not been known why memory T cells not specific for the virus fail to proliferate on exposure to their cognate antigen. Using a lymphocytic choriomeningitis virus (LCMV) infection model in which LCMV-immune Thy 1.1(+) splenocytes are adoptively transferred into Thy 1.2(+) LCMV carrier mice, we demonstrate here that T cells clearly defined as not specific for the virus are sensitized to undergo activation-induced cell death on TCR stimulation in vitro. This bystander sensitization was in part dependent on the expression of Fas ligand (FasL) on the activated virus-specific cells and gamma interferon (IFN-gamma) receptor expression on the bystander T cells. We propose that FasL from highly activated antiviral T cells may sensitize IFN-gamma-conditioned T cells not specific for the virus to undergo apoptosis rather than to proliferate on encountering antigen. This may in part explain the failure of memory T cells to respond to recall antigens during acute and persistent viral infections.

Mucosal immunization of cynomolgus macaques with two serotypes of live poliovirus vectors expressing simian immunodeficiency virus antigens: stimulation of humoral, mucosal, and cellular immunity.

Poliovirus live virus vectors are a candidate recombinant vaccine system. Previous studies using this system showed that a live poliovirus vector expressing a foreign antigen between the structural and nonstructural proteins generates both antibody and cytotoxic T-lymphocyte responses in mice. Here we describe a novel in vitro method of cloning recombinant polioviruses involving a hybrid-PCR approach. We report the construction of recombinant vectors of two different serotypes of poliovirus-expressing simian immunodeficiency virus (SIV) antigens and the intranasal and intravenous inoculations of four adult cynomolgus macaques with these poliovirus vectors expressing the SIV proteins p17(gag) and gp41(env). All macaques generated a mucosal anti-SIV immunoglobulin A (IgA) response in rectal secretions. Two of the four macaques generated mucosal antibody responses detectable in vaginal lavages. Strong serum IgG responses lasting for at least 1 year were detected in two of the four monkeys. SIV-specific T-cell lymphoproliferative responses were detected in three of the four monkeys. SIV-specific cytotoxic T lymphocytes were detected in two of the four monkeys. This is the first report of poliovirus-elicited vaginal IgA or cytotoxic T lymphocytes in any naturally infectable primate, including humans. These findings support the concept that a live poliovirus vector is a potentially useful delivery system that elicits humoral, mucosal, and cellular immune responses against exogenous antigens.

Nasal immunization of nonhuman primates with simian immunodeficiency virus p55gag and cholera toxin adjuvant induces Th1/Th2 help for virus-specific immune responses in reproductive tissues.

Female rhesus macaques were nasally immunized with p55gag (p55) of SIV and cholera toxin as a mucosal adjuvant. Nasal immunization induced Ag-specific IgA and IgG Abs in mucosal secretions (e.g., cervicovaginal secretions, rectal washes, and saliva) and serum. Furthermore, high numbers of p55-specific IgA and IgG Ab-forming cells were induced in mucosal effector sites, i.e., uterine cervix, intestinal lamina propria, and nasal passage. p55-specific CD4+ T cells in both systemic and mucosal compartments expressed IFN-gamma and IL-2 (Th1-type)- as well as IL-5, IL-6, and IL-10 (Th2-type)-specific mRNA. Moreover, p55-specific CTL activity was demonstrated in lymphocytes from blood, tonsils, and other lymphoid tissues. These results show that nasal immunization with SIV p55 with cholera toxin elicits both Th1- and selective Th2-type cytokine responses associated with the induction of SIV-specific mucosal and serum Abs, and CTL activity. These results offer a promise for the development of protective mucosal immunity to SIV.

Apoptotic regulation of T cells and absence of immune deficiency in virus-infected gamma interferon receptor knockout mice.

Acute viral infections often induce a transient period of immune deficiency in which the host's T cells fail to proliferate in response to T-cell mitogens and fail to make an antigen-specific memory recall response. This has been associated with the enhanced sensitivity of these highly activated T cells to undergo apoptosis, or activation-induced cell death (AICD), upon T-cell receptor ligation. Here we show that gamma interferon receptor-deficient (IFN-gamma R-/-) mice mount a T-cell response to lymphocytic choriomeningitis virus (LCMV) infection but fail to undergo the transient immune deficiency. Instead, their T cells were hyperproliferative and relatively, but not completely, resistant to AICD. The immune response returned to homeostasis, but with delayed kinetics, in parallel with delayed clearance of the virus. Wild-type mice receiving high doses of disseminating LCMV Clone 13 are known to undergo clonal exhaustion of their virus-specific cytotoxic T lymphocytes (CTL). To determine whether this process was mediated by AICD associated with IFN-gamma or with Fas-Fas ligand interactions, LCMV-specific precursor CTL frequencies were examined in LCMV Clone 13-infected IFN-gamma R-/- or lpr (Fas-deficient) mice. In both instances, viral persistence was established and CTL precursors were greatly eliminated. This finding indicates that clonal exhaustion of CTL does not require IFN-gamma or Fas, even though both molecules influence AICD and the transient immune deficiency seen in the LCMV infection.

Alpha beta and gamma delta T-cell networks and their roles in natural resistance to viral infections.

Both alpha beta and gamma delta T-cell populations and natural killer (NK) cells include cytotoxic, interferon (IFN)-gamma-producing lymphocytes that actively respond to viral infections. We show here that all three populations can provide "natural resistance" to viruses very early in infection and describe how the T-cell populations are modulated to provide this function. gamma delta T cells were shown to play a role in controlling vaccinia virus (VV) infections, as VV grew to much higher titers in gamma delta T-cell knockout mice than in normal mice 3-4 days post-infection. Our studies of the alpha beta T-cell responses to viruses revealed an interactive network of T cells that is modulated substantially during systemic infections. There is an induction phase associated with a massive virus-specific CD8 T-cell response, an apoptosis phase during which the T cells become sensitized to activation-induced cell death (AICD), a silencing phase, during which the T-cell number and activation state is reduced, and, finally, a memory phase associated with the very stable preservation of virus-specific memory cytotoxic T-lymphocyte precursors (pCTL). Infection of mice immune to one virus with a heterologous virus leads to a selective expansion of memory CTL cross-reacting between the two viruses, but, after homeostasis is again established, there is a quantitative reduction and qualitative alteration of memory to the first virus. Our results suggest that memory alpha beta T cells cross-reactive between heterologous viruses mediate both immunopathology and protective immunity at early stages of the second virus infection. Thus, memory alpha beta T cells can, like gamma delta T cells and NK cells, provide natural immunity to viral infections.

T-lymphocyte downregulation after acute viral infection is not dependent on CD95 (Fas) receptor-ligand interactions.

Infection of mice with lymphocytic choriomeningitis virus (LCMV) causes a major expansion of CD8+ T cells followed by a period of immune downregulation that coincides with the induction of lymphocyte apoptosis in the mouse spleen. CD95 (Fas) and its ligand are important for regulating peripheral T-lymphocyte numbers and can mediate apoptosis of mature T lymphocytes. We infected CD95- and CD95L-deficient mice (lpr and gld, respectively) with LCMV to determine if the immune downregulation that occurred following resolution of the LCMV infection was due to a CD95-dependent apoptotic mechanism. Lymphocytes from LCMV-infected lpr and gld mice were capable of normal T-cell expansion and cytolytic function but were, in contrast to activated cells from normal virus-infected mice, relatively more resistant to T-cell receptor-induced apoptosis in vitro. However, in vivo there were significant numbers of apoptotic cells in the spleens of lpr and gld mice recovering from the infection, and the T-cell number and cytolytic activity decreased to normal postinfection levels. Thus, CD95 is not required for the immune downregulation of the CD8+-T-lymphocyte response following acute LCMV infection.