Early expression of the type III secretion system of Parachlamydia acanthamoebae during a replicative cycle within its natural host cell Acanthamoeba castellanii.

The type three secretion system (T3SS) operons of Chlamydiales bacteria are distributed in different clusters along their chromosomes and are conserved at both the level of sequence and genetic organization. A complete characterization of the temporal expression of multiple T3SS components at the transcriptional and protein levels has been performed in Parachlamydia acanthamoebae, replicating in its natural host cell Acanthamoeba castellanii. The T3SS components were classified in four different temporal clusters depending on their pattern of expression during the early, mid- and late phases of the infectious cycle. The putative T3SS transcription units predicted in Parachlamydia are similar to those described in Chlamydia trachomatis, suggesting that T3SS units of transcriptional expression are highly conserved among Chlamydiales bacteria. The maximal expression and activation of the T3SS of Parachlamydia occurred during the early to mid-phase of the infectious cycle corresponding to a critical phase during which the intracellular bacterium has (1) to evade and/or block the lytic pathway of the amoeba, (2) to differentiate from elementary bodies (EBs) to reticulate bodies (RBs), and (3) to modulate the maturation of its vacuole to create a replicative niche able to sustain efficient bacterial growth.

RTOG 0525: Exploratory Subset Analysis from a Randomized Phase III Trial Comparing Standard (std) Adjuvant Temozolomide (TMZ) with a Dose-dense (dd) Schedule for Glioblastoma (GBM)

Purpose/Objective(s): RTwith TMZ is the standard for GBM. dd TMZ causes prolongedMGMTdepletion in mononuclear cells and possibly in tumor. The RTOG 0525 trial (ASCO 2011) did not show an advantage from dd TMZ for survival or progression free survival. We conducted exploratory, hypothesis-generating subset analyses to detect possible benefit from dd TMZ.Materials/Methods: Patients were randomized to std (150-200 mg/m2 x 5 d) or dd TMZ (75-100 mg/m2 x 21 d) q 4 weeks for 6- 12 cycles. Eligibility included age.18, KPS$ 60, and. 1 cm2 tissue for prospective MGMTanalysis for stratification. Furtheranalyses were performed for all randomized patients (''intent-to-treat'', ITT), and for all patients starting protocol therapy (SPT). Subset analyses were performed by RPA class (III, IV, V), KPS (90-100, = 50,\50), resection (partial, total), gender (female, male), and neurologic dysfunction (nf = none, minor, moderate).Results: No significant difference was seen for median OS (16.6 vs. 14.9 months), or PFS (5.5 vs. 6.7 months, p = 0.06). MGMT methylation was linked to improved OS (21.2 vs. 14 months, p\0.0001), and PFS (8.7 vs. 5.7 months, p\0.0001). For the ITT (n = 833), there was no OS benefit from dd TMZ in any subset. Two subsets showed a PFS benefit for dd TMZ: RPA class III (6.2 vs. 12.6 months, HR 0.69, p = 0.03) and nf = minor (HR 0.77, p = 0.01). For RPA III, dd dramatically delayed progression, but post-progression dd patients died more quickly than std. A similar pattern for nf = minor was observed. For the SPT group (n = 714) there was neither PFS nor OS benefit for dd TMZ, overall. For RPA class III and nf = minor, there was a PFS benefit for dd TMZ (HR 0.73, p = 0.08; HR 0.77, p = 0.02). For nf = moderate subset, both ITT and SPT, the std arm showed superior OS (14.4 vs. 10.9 months) compared to dd, without improved PFS (HR 1.46, p = 0.03; and HR 1.74, p = 0.01. In terms of methylation status within this subset, there were more methylated patients in the std arm of the ITT subset (n = 159; 32 vs. 24%). For the SPT subset (n = 124), methylation status was similar between arms.Conclusions: This study did not demonstrate improved OS for dd TMZ for any subgroup, but for 2 highly functional subgroups, PFS was significantly increased. These data generate the testable hypothesis that intensive treatment may selectively improve disease control in those most likely able to tolerate dd therapy. Interpretation of this should be considered carefully due to small sample size, the process of multiple observations, and other confounders.Acknowledgment: This project was supported by RTOG grant U10 CA21661, and CCOP grant U10 CA37422 from the National Cancer Institute (NCI).

Orthogonal higher order structure and confirmatory factor analysis of the French Wechsler Adult Intelligence Scale (WAIS-III).

According to the most widely accepted Cattell-Horn-Carroll (CHC) model of intelligence measurement, each subtest score of the Wechsler Intelligence Scale for Adults (3rd ed.; WAIS-III) should reflect both 1st- and 2nd-order factors (i.e., 4 or 5 broad abilities and 1 general factor). To disentangle the contribution of each factor, we applied a Schmid-Leiman orthogonalization transformation (SLT) to the standardization data published in the French technical manual for the WAIS-III. Results showed that the general factor accounted for 63% of the common variance and that the specific contributions of the 1st-order factors were weak (4.7%-15.9%). We also addressed this issue by using confirmatory factor analysis. Results indicated that the bifactor model (with 1st-order group and general factors) better fit the data than did the traditional higher order structure. Models based on the CHC framework were also tested. Results indicated that a higher order CHC model showed a better fit than did the classical 4-factor model; however, the WAIS bifactor structure was the most adequate. We recommend that users do not discount the Full Scale IQ when interpreting the index scores of the WAIS-III because the general factor accounts for the bulk of the common variance in the French WAIS-III. The 4 index scores cannot be considered to reflect only broad ability because they include a strong contribution of the general factor.

Insuffisance veineuse chronique stade III: Prise en charge physio- thérapeutique [3rd degree chronic venous insufficiency: physiotherapy treatment]

A venous ulcer is the end result of a long pathological process where venous hypertension represents the principal cause of a number of complications. The physiotherapist by adapting various different therapeutic approaches improves the vascular, joint and respiratory problems of these patients.

Ecology of mosquitoes (Diptera: Culicidae) in areas of Serra do Mar State Park, State of São Paulo, Brazil. III - daily biting rhythms and lunar cycle influence

The ecology of mosquito species (Diptera: Culicidae) was studied in areas of the Serra do Mar State Park, State of São Paulo, Brazil. The influence of the lunar cycle and the daily biting rhythms of mosquito populations were analyzed. Systematized biweekly human bait collections were made in a silvatic environment for 24 consecutive months (January 1991 to December 1992). A total of 20,591 specimens of adult mosquitoes belonging to 55 species were collected from 545 catches. Sabethini species were captured exclusively during daylight periods, with the exception of Trichoprosopon digitatum, while members of Anophelinae predominated during nocturnal hours. Members of the subfamily Culicinae that were collected primary during nocturnal periods included Culex nigripalpus, Coquillettidia chrysonotum and Cq. venezuelensis while daytime catches included Psorophora ferox and Ps. albipes. Others members of culicines mosquitoes that were collected during both day and night included: Aedes serratus, Ae. scapularis and Ae. fulvus. Lunar cycles did not appear to influence the daily biting rhythms of most mosquito species in the area, but larger numbers of mosquitoes were collected during the new moon. Ae. scapularis were captured mainly during the full moon.

Concomitant cisplatin and hyperfractionated radiotherapy in locally advanced head and neck cancer: 10-year follow-up of a randomized phase III trial (SAKK 10/94).

Purpose: To compare the long-term outcome of treatment with concomitant cisplatin and hyperfractionated radiotherapy versus treatment with hyperfractionated radiotherapy alone in patients with locally advanced head and neck cancer.Methods and Materials: From July 1994 to July 2000, a total of 224 patients with squamous cell carcinoma of the head and neck were randomized to receive either hyperfractionated radiotherapy alone (median total dose, 74.4 Gy; 1.2 Gy twice daily; 5 days per week) or the same radiotherapy combined with two cycles of cisplatin (20 mg/m(2) for 5 consecutive days during weeks 1 and 5). The primary endpoint was the time to any treatment failure; secondary endpoints were locoregional failure, metastatic failure, overall survival, and late toxicity assessed according to Radiation Therapy Oncology Group criteria.Results: Median follow-up was 9.5 years (range, 0.1-15.4 years). Median time to any treatment failure was not significantly different between treatment arms (hazard ratio [HR], 1.2 [95% confidence interval [CM 0.9-1.7; p = 0.17]). Rates of locoregional failure-free survival (HR, 1.5 [95% CI, 1.1-2.1;p = 0.021), distant metastasis-free survival (HR, 1.6 [95% CI, 1.1-2.5; p = 0.021), and cancer-specific survival (HR, 1.6 [95% CI, 1.0-2.5;p = 0.03]) were significantly improved in the combined-treatment arm, with no difference in major late toxicity between treatment arms. However, overall survival was not significantly different (HR, 1.3 [95% CI, 0.9-1.8; p = 0.11]).Conclusions: After long-term follow-up, combined-treatment with cisplatin and hyperfractionated radiotherapy maintained improved rates of locoregional control, distant metastasis-free survival, and cancer-specific survival compared to that of hyperfractionated radiotherapy alone, with no difference in major late toxicity. (C) 2012 Elsevier Inc.

Pràctiques i rituals funeraris a Tàrraco i el seu ager (segles II aC-III/IV dC)

L’objectiu d’aquest projecte ha estat identificar i analitzar els rituals funeraris a celebrats als suburbis de Tàrraco i el seu territorium. Per tal d’assolir-lo hem revisat col•leccions de museus, arxius i informes arqueològics arribant a documentar 721 enterraments. A través de la recerca, hem estudiat les peculiaritats i els elements d’aixovar que les tombes presenten amb el suport de les fonts escrites. Hem detectat pràctiques rituals com ara libacions, sacrificis i objectes relacionats amb ofrenes funeràries a l’exterior de les tombes. Hem documentat certa una uniformitat general i repetiva pel que fa a la selecció dels aixovars funerari. No obstant això, hi ha algunes diferències sobretot en aixovars que provenen de les tombes d’individus morts prematurament (individus no casats, infants). També s’ha constatat una diferència sexual entre dones i homes pel que fa als objectes d’aixovar. Hem utilitzat l’evidència arqueològica i literària per tal de trobar el significat d’aquests artefactes quotidians que canvien de significat quan entren en contacte amb els morts. En revisar la informació procedent d’excavacions hem identificat espais rituals específics dins de la necròpolis com jardins funeraris i ustrina. Aquest estudi ha explorat la manera com l’arqueologia ens permeten identificar les pràctiques rituals dins les àrees funeràries. L’estudi de materials arqueològics documentats als estrats de freqüentació de les necròpolis ens ha permès detectar l’evidència material de la ritualitat.

Schistosomiasis mansoni in Bananal (State of São Paulo, Brazil): III. Seroepidemiological studies in the Palha District

The Palha district, municipality of Bananal, State of São Paulo, Brazil, had 10.3% cases of Schistosoma mansoni diagnosed from 1994 to 2000 by coproscopy: about three times the municipality average. The immunofluorescent antibody test was used to assess gut-associated IgM antibody titers of samples from 452 inhabitants. It disclosed 129 (28.5%) positive cases. Subjects were classified according to age, sex, birthplace, and period of residence. Titers varied from 8 to 4,096 (geometric mean: 170.2). Seropositives were aged from 6 to 69 years (average: 24.5), 75% of them aged 34 or less, predominantly males (78 or 60.5%). Of all subjects, 65.7% were born and had been living in Bananal since; 24.2% came from neighboring municipalities and are residing in Bananal from two months to 89 years (average: 22.7 years). Further Kato-Katz coproscopy from 97 seropositives (geometric mean titer, 619) revealed S. mansoni eggs in 11 subjects (11.3%). Serology was deemed useful in screening subjects to be further investigated by coproscopy, considering that blood collection had better acceptance than supplying fecal samples. Higher than average serological titers may indicate new cases in endemic areas. Longitudinal studies associated with epidemiological investigation, including titer evolution are advised, as isolated data are difficult to interpret.

Freshwater snails and Schistosomiasis mansoni in the state of Rio de Janeiro, Brazil: III - Baixadas Mesoregion

In this paper, the third of a series dealing with the survey of freshwater gastropods of the state of Rio de Janeiro, the results of collections carried out in the Mesoregion Baixadas from 2000 to 2002 are presented. Twenty-two species, belonging to seven families, were found. As to the snail intermediate hosts of Schistosoma mansoni, the most frequent species was Biomphalaria tenagophila besides some new findings of Biomphalaria straminea. No specimens were found harboring larval forms of S. mansoni although different kinds of cercariae had been observed.

Human papillomavirus prevalence among women with cervical intraepithelial neoplasia III and invasive cervical cancer from Goiânia, Brazil

This study estimated the prevalence and distribution of human papillomavirus (HPV) types among women with cervical intraepithelial neoplasia (CIN) grade III and invasive cervical cancer from Goiás (Brazil Central Region). Seventy-four cases were analyzed and consisted of 18 CIN III, 48 squamous cell carcinomas, 4 adenocarcinomas, 1 adenosquamous carcinoma and 3 undifferentiated carcinomas. HPV-DNA sequences were examined in formalin-fixed and paraffin-embedded tissues using primers from L1 region GP5+/GP6+. Polymerase chain reaction products were typed with dot blot hybridization using probes for HPV 16, 18, 31, 33, 45, 54, 6/11, 42/43/44, 51/52, 56/58. The prevalence of HPV was estimated to be 76% (56/74). HPV 16 was the most frequently found type, followed by HPV 33, 18 and 31. The prevalence of untyped HPV was 6%; 79% percent of the squamous cell carcinoma cases and 61% percent of the CIN III were positive for HPV and the prevalence rate of HPV types was the same for the total number of cases. According to other studies, HPV type 16 is the most prevalent virus in all Brazilian regions, but there is variation regarding to other types. Type 18 is the second most prevalent HPV in North, Southeast and South Brazil regions and types 31 and 33 are the second most prevalent HPV in Northeast and Central Brazil, respectively.

Triatoma rubrovaria (Blanchard, 1843) (Hemiptera-Reduviidae-Triatominae) III: patterns of feeding, defecation and resistance to starvation

Data from the Chagas Disease Control Program indicate a growing domiciliary and peridomiciliary invasion of Triatoma rubrovaria in the State of Rio Grande do Sul, where it has become the most frequent triatomine species captured there since the control of T. infestans. Bionomic characteristics that could influence the vectorial capacity of T. rubrovaria as vector of Trypanosoma cruzi were evaluated: patterns of (i) feeding, (ii) defecation, and (iii) resistance to starvation, using insects fed on mice. Fifty three percent of the females showed a defecation pattern conducive to chagasic transmission, defecating either on or near the bite site. The averages of the resistance to starvation varied from 48.1 to 179 days, for the first and fifth nymphal stages, respectively. Our study shows that with respect to the patterns of feeding, defecation and resistance to fasting, T. rubrovaria presented similar rates to the ones observed for other effective vector species, such as T. infestans. Thus, based on our studies we conclude that T. rubrovaria has biological characteristics that can positively influence its capacity to become infected and transmit T. cruzi, and also to keep residual populations after chemical control interventions.

Toxicity at three years with and without irradiation of the internal mammary and medial supraclavicular lymph node chain in stage I to III breast cancer (EORTC trial 22922/10925).

INTRODUCTION: The EORTC 22922/10925 trial investigated the potential survival benefit and toxicity of elective irradiation of the internal mammary and medial supraclavicular (IM-MS) nodes Accrual completed in January 2004 and first results are expected in 2012. We present the toxicity reported until year 3 after treatment. PATIENTS AND METHODS: At each visit, toxicity was reported but severity was not graded routinely. Toxicity rates and performance status (PS) changes at three years were compared by chi(2) tests and logistic regression models in all the 3,866 of 4,004 patients eligible to the trial who received the allocated treatment. RESULTS: Only lung (fibrosis; dyspnoea; pneumonitis; any lung toxicities) (4.3% vs. 1.3%; p < 0.0001) but not cardiac toxicity (0.3% vs. 0.4%; p = 0.55) significantly increased with IM-MS treatment. No significant worsening of the PS was observed (p = 0.79), suggesting that treatment-related toxicity does not impair patient's daily activities. CONCLUSIONS: IM-MS irradiation seems well tolerated and does not significantly impair WHO PS at three years. A follow-up period of at least 10 years is needed to determine whether cardiac toxicity is increased after radiotherapy.