Impact of mother donor, peripheral blood stem cells and measurable residual disease on outcomes after haploidentical hematopoietic cell transplantation with post-transplant cyclophosphamide in children with acute leukaemia.

Haploidentical hematopoietic-cell transplantation using post-transplant cyclophosphamide(Haplo-PTCy) is a feasible procedure in children with haematologic malignancies. However, data of a large series of children with acute leukaemia(AL) in this setting is missing. We analysed 144 AL Haplo-PTCy paediatric recipients; median age was 10 years. Patients had acute lymphoblastic(ALL; n = 86) or myeloblastic leukaemia(AML; n = 58) and were transplanted in remission(CR1: n = 40; CR2: n = 57; CR3+: n = 27) or relapse (n = 20). Bone marrow was the graft source in 57%; donors were father (54%), mother (35%), or sibling (11%). Myeloablative conditioning was used in 87%. Median follow-up was 31 months. At day +100, cumulative incidence (CI) of neutrophil recovery and acute GVHD (II-IV) were 94% and 40%, respectively. At 2-years, CI of chronic GVHD and relapse, were 31%, 40%, and estimated 2-year overall survival (OS), leukaemia-free survival (LFS) and graft-versus-host-relapse-free survival (GRFS) were 52%, 44% and 34% respectively. For patients transplanted in remission, positive measurable residual disease (MRD) prior to transplant was associated with decreased LFS (p = 0.05) and GRFS (p = 0.003) and increased risk of relapse (p = 0.02). Mother donor was associated with increased risk of chronic GVHD (p = 0.001), decreased OS (p = 0.03) and GRFS (p = 0.004). Use of PBSC was associated with increased risk of chronic GVHD (p = 0.04). In conclusion, achieving MRD negativity pre-transplant, avoiding use of mother donors and PBSC as graft source may improve outcomes of Haplo-PTCy in children with AL.

DNA Mismatch Repair-Deficient Colorectal Carcinoma: Referral Rate for Genetic Cancer Risk Assessment in a Brazilian Cancer Center.

BACKGROUND: Approximately 15% of colorectal cancers (CRCs) are deficient in DNA mismatch repair proteins (dMMR), a characteristic that can occur in both sporadic and hereditary CRC. Due to sparse studies on dMMR CRC in the Brazilian population, we conducted a retrospective analysis of referral rates for Genetic Cancer Risk Assessment of this population and also describing clinical and molecular characterization of these tumors. METHODS: A retrospective, longitudinal, and unicenter study that included patients with dMMR CRC detected by IHC analysis from Pathology Database of our institution, from January 2015 to July 2017. RESULTS: MMR IHC testing was performed in 998 CRC tumors, and 78 tumors (7.8%) had dMMR. The mean age at diagnosis was 56.8 years (17-90), and most patients were female (41 out of 78, 52.6%). Of the 52 patients with right-sided CRC, 40 tumors (77%) had loss of the MLH1 and/or PMS2 expression, and 12 tumors (23%) had loss of MSH2 and/or MSH6 expression (p = 0.005). From 78 patients with dMMR CRC, only 43 patients (55.1%) were referred for genetic counseling (GC), and of them, only 33 patients (76.7%) really went to GC consultation. A total of 21 patients with dMMR CRC performed genetic testing. CONCLUSION: Overall, genetic referral was less than expected in our population. Most of dMMR CRC patients did not receive GC, even in a cancer center, either due to the absence of referral or personal decision and few patients who pursued genetic counseling performed genetic testing.

Occurrence of Neospora caninum and Toxoplasma gondii DNA in brain tissue from hoary foxes (Pseudalopex vetulus) in Brazil.

The hoary fox (Pseudalopex vetulus) is a wild canid native to Brazil and is commonly found in the semiarid northeastern area living in contact with cattle. The main purpose of this study was to investigate the presence of Neospora caninum and Toxoplasma gondii DNA in hoary foxes, in the state of Paraíba, Brazil. Brain tissue samples were collected from 49 hoary foxes. From the samples, DNA extraction and the polymerase chain reaction (PCR) were performed using specific primers for N. caninum and T. gondii. The prevalences found were 14.3% (7/49) for T. gondii and 12.2% (6/49) for N. caninum. The molecular identities of the amplified products were confirmed by means of the sequencing reaction. This study demonstrated the presence of N. caninum and T. gondii DNA in free-ranging hoary foxes in Brazil for the first time, thus confirming that this species is an intermediate host.

Motor strategy patterns study of diabetic neuropathic individuals while walking. A wavelet approach.

The aim of this study was to investigate muscle׳s energy patterns and spectral properties of diabetic neuropathic individuals during gait cycle using wavelet approach. Twenty-one diabetic patients diagnosed with peripheral neuropathy, and 21 non-diabetic individuals were assessed during the whole gait cycle. Activation patterns of vastus lateralis, medial gastrocnemius and tibialis anterior were studied by means of bipolar surface EMG. The signal׳s energy and frequency were compared between groups using t-test. The energy was compared in each frequency band (7-542 Hz) using ANOVAs for repeated measures for each group and each muscle. The diabetic individuals displayed lower energies in lower frequency bands for all muscles and higher energies in higher frequency bands for the extensors׳ muscles. They also showed lower total energy of gastrocnemius and a higher total energy of vastus, considering the whole gait cycle. The overall results suggest a change in the neuromuscular strategy of the main extensor muscles of the lower limb of diabetic patients to compensate the ankle extensor deficit to propel the body forward and accomplish the walking task.

Effect of the inoculation level of Lactobacillus acidophilus in probiotic cheese on the physicochemical features and sensory performance compared with commercial cheeses.

The complex metabolism of probiotic bacteria requires several technological options to guarantee the functionally of probiotic dairy foods during the shelf life. This research aimed to evaluate the effect of the supplementation of increasing amounts of Lactobacillus acidophilus (0, 0.4, or 0.8 g/L of milk) on the physicochemical parameters and sensory acceptance of Minas fresh cheese. In addition, the sensory acceptance of probiotic cheeses was assessed using a consumer test and compared with commercial cheeses (conventional and probiotic). High counts (9.11 to 9.42 log cfu/g) of L. acidophilus were observed throughout the shelf life, which contributed to the maintenance of its probiotic status and resulted in lower pH values and greater production of organic acids. The probiotic cheeses presented lower scores for appearance, aroma, and texture compared with conventional cheeses. Internal preference mapping explained almost 60% of the total variation of the data and showed a large number of consumers concentrated near the conventional cheeses, demonstrating greater preference for these samples. The findings indicated that some negative sensory effects could occur when high level of supplementation with L. acidophilus is used in probiotic cheese processing.

Mother's personality and infant temperament.

We examined if perfectionism and the perception of being an anxious person were associated with more negative infant temperament ratings by the mothers. 386 women (mean age=30.08; standard deviation=4.21) in their last trimester of pregnancy completed the Multidimensional Perfectionism Scale (MPS), the Beck Depression Inventory-II (BDI-II) and an item about their perception of being or not an anxious person. The Portuguese version of the Diagnostic Interview for Genetic Studies and the Operational Criteria Checklist for Psychotic Illness were used to generate diagnoses according to DSM-IV and ICD-10 criteria. After delivery, women completed eight items of the Difficult Infant Temperament Questionnaire (developed by our team) and filled in, again, the BDI-II and were interviewed with the DIGS. Women with depression (DSM-IV/ICD-10) and probable cases of depression using different cut-offs adjusted to Portuguese prevalence (BDI-II), in pregnancy and postpartum, were excluded. The Difficult Infant Temperament Questionnaire showed to have factorial validity and internal consistency. There was a statistically significant negative correlation between perfectionism total scale score and item 6 from the temperament scale ("is your baby irritable or fussy?"). Considering MPS 3-factor solution found for pregnancy there was also a statistically significant negative correlation between SOP and the same item. Women with low SOP differed from those with medium and high SOP in the total temperament score. Moreover, the low SOP group differed from the medium group on items three and four scores. There were no significant associations with SPP, which is the dimension more closely associated with negative outcomes. There was an association between anxiety trait status (having it or not) and scoring low, medium or high in the infant temperament scale. The proportion of anxious vs. non-anxious women presenting a high score on the infant temperament scale was higher (24.2% vs. 12.9%). Linear regressions showed that SOP (low vs. medium/high) offered a significant contribution to the prediction of total temperament scale score and items 3 and 4 scores, but a logistic regression did not confirm trait anxiety as a significant predictor of mother's infant temperament perception. Concluding, a major result concerns the fact that higher levels of adaptive perfectionism (i.e. SOP) are associated (and predict) a less negative view of their infant's temperament. These results on the effect of mother's anxiety and perfectionism on the child temperament perception might have treatment implications. As perfectionism is not always maladaptive, some of its positive features could be used to enhance women's self-efficacy/sense of parental competence in their role as mothers and positive affect towards their infants. Also, antenatal interventions aimed at minimising anxiety could help to optimise infant temperament outcomes, which could, eventually, also, lead to subsequent maternal and infant mental health better outcomes.

Validation of a Leishmania infantum ELISA rapid test for serological diagnosis of Leishmania chagasi in dogs.

Canine visceral leishmaniasis (CVL) is caused by Leishmania donovani complex parasites including L. donovani, Leishmania infantum and Leishmania chagasi. As some studies suggest that L. chagasi and L. infantum may be very similar or even the same species, the aim of the present study was to evaluate a commercial rapid ELISA test, originally designed for L. infantum, in the diagnosis of CVL in dogs naturally infected by L. chagasi. A total of 400 serum canine samples, including 283 positive dogs for CVL from an endemic area, 86 clinically healthy dogs from a non-endemic area and 31 dogs seropositive for confounding infectious agents (Trypanosoma cruzi, Toxoplasma gondii, Neospora caninum, Babesia canis and Ehrlichia canis) were used for test validation. An overall sensitivity of 94.7% (95% CI=91.41-97.01%) and specificity of 90.6% (95% CI=83.80-95.21%) was found, with a high degree of agreement (k=0.8445) to the indirect ELISA. When confounding infectious diseases were excluded, specificity increased to 100% (95% CI=95.8-100%), with a higher degree of agreement (k=0.8928). In conclusion, the commercial kit designed for L. infantum was a highly sensitive and specific device for detection of L. chagasi infection in dogs, which indicates high immunoreactivity similarities between L. infantum and L. chagasi.

Role of ankle mobility in foot rollover during gait in individuals with diabetic neuropathy.

BACKGROUND: The purpose of this study was to investigate the ankle range of motion during neuropathic gait and its influence on plantar pressure distribution in two phases during stance: at heel-strike and at push-off. METHODS: Thirty-one adults participated in this study (control group, n=16; diabetic neuropathic group, n=15). Dynamic ankle range of motion (electrogoniometer) and plantar pressures (PEDAR-X system) were acquired synchronously during walking. Plantar pressures were evaluated at rearfoot, midfoot and forefoot during the two phases of stance. General linear model repeated measures analysis of variance was applied to investigate relationships between groups, areas and stance phases. FINDINGS: Diabetic neuropathy patients walked using a smaller ankle range of motion in stance phase and smaller ankle flexion at heel-strike (P=0.0005). Peak pressure and pressure-time integral values were higher in the diabetic group in the midfoot at push-off phase when compared to heel-strike phase. On the other hand, the control group showed similar values of peak pressure in midfoot during both stance phases. INTERPRETATION: The ankle mobility reduction observed could be associated to altered plantar pressure distribution observed in neuropathic subjects. Results demonstrated that midfoot and forefoot play a different role in subjects with neuropathy by receiving higher loads at push-off phase that are probably due to smaller ankle flexion at stance phase. This may explain the higher loads in anterior areas of the foot observed in diabetic neuropathy subjects and confirm an inadequate foot rollover associated to the smaller ankle range of motion at the heel-strike phase.

Avaliação das perdas sensório-motoras do pé e tornozelo decorrentes da neuropatia diabética / Assessment of motor sensory losses in the foot and ankle due to diabetic neuropathy

OBJETIVOS: Identificar déficits sensório-motores de pés de pacientes diabéticos neuropatas e comparar os déficits do grupo neuropata com um grupo de sujeitos saudáveis. MÉTODO: 49 diabéticos neuropatas (GD) e 22 controles foram submetidos a um protocolo de três estágios: (1) entrevista por meio de questionário, que caracterizou a neuropatia e sintomas, (2) avaliação da função muscular, amplitude de movimentos e testes funcionais dos pés e tornozelos, (3) avaliação da sensibilidade tátil e térmica. Os grupos foram comparados por meio dos testes Qui-quadrado, Mann-Withney e Teste T (p<0,05). RESULTADOS: O GD mostrou perda significativa das sensibilidades tátil e térmica em comparação ao grupo controle, principalmente nos calcanhares (49,0 por cento no GD e 97,3 por cento no GC). A função muscular está diminuída no GD, com predomínio da perda do grau 5. Os músculos mais afetados são os interósseos (23,4 por cento), extensor do hálux (42,5 por cento) e tríceps sural (43,2 por cento), enquanto que o GC teve todos os músculos preservados. Todas as ADMs do GD estão diminuídas em relação ao GC. O GD apresentou os testes funcionais de tornozelo diminuídos em 50 por cento. CONCLUSÃO: Houve diferenças significativas entre os grupos quanto às perdas sensitivas, de função muscular, amplitude de movimento e funcionais. Essas diferenças podem ser atribuídas à neuropatia diabética.

OBJECTIVE: To identify motor sensory deficits in the feet of neuropathic diabetic patients and compare their deficits with a group of healthy subjects. METHOD: 49 neuropathic diabetics (group NG) and 22 controls (group CG) underwent a three-stage protocol: (1) an interview using a questionnaire to characterize the neuropathy and symptoms; (2) assessment of muscle function and range of motion, and functional tests on the feet and ankles; (3) assessment of tactile and thermal sensitivity. The groups were compared using the chi-squared, Mann-Whitney and Student t tests (p<0.05). RESULTS: NG presented significant losses of tactile and thermal sensitivity in comparison with CG, especially in the heels (49.0 percent of NG and 97.3 percent of CG). Muscle function was decreased in NG, with predominance of loss of grade 5. The muscles most affected were the interossei (23.4 percent), extensor hallucis (42.5 percent) and triceps surae (43.2 percent), while all muscle function was preserved in CG. All ranges of motion in NG were reduced in comparison with CG. The functional tests on the ankles in NG presented a decrease of around 50 percent. CONCLUSION: There were significant differences between the groups with regard to sensitivity, muscle function, range of motion and functional losses. These differences can be attributed to the diabetic neuropathy.

Genetic and phylogenetic characterization of rabies virus isolates from wildlife and livestock in Paraiba, Brazil.

Thirty-four rabies virus (RV) isolates from foxes (8), insectivore bats (9), cattle (14), sheep (1), a goat (1) and a donkey (1) from Paraiba state, northeastern Brazil, were genetically characterized. Sequences of 890 nts of nucleoprotein (N) genes of these isolates were analyzed and compared with those of other Brazilian isolates characterized earlier. Phylogenetic analysis revealed three genetical lineages of RV co-existing in this region. Each lineage was found to be associated with particular host species and to circulate independently of each other. The first lineage was found in foxes (Dusicyon sp.) and could be discriminated from domestic carnivore isolates from Sao Paulo, Goias and Minas Gerais in the southern and central Brazil. The second lineage was associated with insectivorous bats (Molossus spp.) and differed from vampire bat-associated RV isolates. The third lineage was found in livestock and clustered with vampire bat-associated RV isolates from Sao Paulo, Tocantins, Goias and Matto Grosso. These results indicate that RV of these genetic lineages are cocirculating in the Paraiba state and that livestock in this region are infected with vampire bat-associated RV, suggesting that the vampire bat is the main reservoir of livestock rabies in this region.

Antigenic and genetic characterization of rabies viruses isolated from domestic and wild animals of Brazil identifies the hoary fox as a rabies reservoir.

Fifty Brazilian rabies viruses, collected from many different animal species and several regions of the country, were characterized by partial sequencing of the central, variable region of the P gene, a locus useful for sensitive molecular epidemiological studies. Phylogenetic analysis of the sequences, which included comparison with other rabies strains recovered from throughout the Americas, identified three main groups of Brazilian viruses, arbitrarily designated BRL-1 to BRL-3. BRL-1 was found in terrestrial carnivores and clusters with other American strains of the cosmopolitan lineage. BRL-2 comprised two distinct isolates, recovered from two species of non-haematophagous bats, that had evolutionary links to insectivorous-bat-derived strains of North America. BRL-3 consisted of isolates from vampire bats and from livestock species probably infected via contact with vampire bats. The terrestrial group was further subdivided into three subtypes: BRL-1a was associated exclusively with dogs and cats, while BRL-1b and BRL-1c were found exclusively in hoary foxes. These observations strongly support the role of the Brazilian hoary fox as a rabies reservoir. Screening of representative Brazilian rabies viruses against a collection of anti-rabies monoclonal antibodies (mAbs) identified a small panel of mAbs that could be used to discriminate between all Brazilian subgroups as defined by genetic classification in this study.

Reactive oxygen species mediate lethality induced by far-UV in Escherichia coli cells.

The involvement of reactive oxygen species (ROS) in the induction of DNA damage to Escherichia coli cells caused by UVC (254 nm) irradiation was studied. We verified the expression of the soxS gene induced by UVC (254 nm) and its inhibition by sodium azide, a singlet oxygen (1O2) scavenger. Additional results showed that a water-soluble carotenoid (norbixin) protects against the lethal effects of UVC. These results suggest that UVC radiation can also cause ROS-mediated lethality.

Does UVB radiation induce SoxS gene expression in Escherichia coli cells?

The SoxRS regulon is induced when bacterial cells are exposed to redox-cycling agents such as menadione or paraquat. In this paper it is shown that a physical agent, such as ultraviolet radiation with a wavelength of 312 nm (UVB) can induce soxS gene expression. The results indicate that this induction involves the RpoS protein. Moreover, an unexpected increase of soxS gene expression independent of a functional soxR gene in UVB-irradiated cells has been verified. This increase could be explained by transcription of soxS gene in a rpoS-dependent pathway.

Detection of antibodies to Neospora caninum in two species of wild canids, Lycalopex gymnocercus and Cerdocyon thous from Brazil.

Domestic dog (Canis domesticus) and the coyote (Canis latrans) are the only known definitive hosts for the protozoan Neospora caninum that causes abortion in dairy cattle. In the present study, antibodies to N. caninum were sought in three species of wild canids, Cerdocyon thous, Lycalopex gymnocercus and Dusicyon vetulus from Brazil. Antibodies to N. caninum were assayed by the indirect fluorescent antibody test (IFAT) and the Neospora agglutination test (NAT). N. caninum antibodies were found in five of 12 L. gymnocercus with IFAT titers of 1:50 in three, 1:100 in one, and 1:1600 in one, and NAT titers of 1:40, 1:80, 1:160, 1:320, and 1:640 in five animals. Antibodies to N. caninum were found in four of 15 C. thous with IFAT titers of 1:50 in one, and 1:100 in three, and NAT titer of 1:40 in one animal. All 30 D. ventulus were seronegative by IFAT and NAT.

Effect of a booster-dose of rabies vaccine on the duration of virus neutralizing antibody titers in bovines.

Humoral immune response using inactivated rabies vaccine was studied in 35 nelore cross-bred bovines of western region of São Paulo state. Ninety days after vaccination, 13 (92.8%) animals presented titers > or = 0.5 IU/ml, through mouse neutralization test. After 180 days, 9 (64.3%) sera showed titers > or = 0.5 IU/ml, after 270 days, only one (7.1%) showed a titer of 0.51 IU/ml, and after 360 days, all animals showed titers < 0.5 IU/ml. Group of animals receiving booster dose 30 days after vaccination presented, two months after, all with titers > 0.5 IU/ml. At 180 days, 17 (80.9%) sera presented titers > 0.5 IU/ml; at 270 days, 15 (71.4%), with titers > or = 0.5 IU/ml and at 360 days, 4 (19.0%), with titers > or = 0.5 IU/ml. Booster-dose ensured high levels of neutralizing antibodies for at least three months, and 240 days after revaccination, 71.4% of animals were found with titers > or = 0.5 IU/ml.

[The terminal patient and psychotherapeutic approach]. / A problemática do doente terminal e a atitude psicoterapêutica.

The end stage situation, namely AIDS and malignant diseases, patients are analysed by the authors from the psychiatric and psychologic standpoint. A multidisciplinary clinical approach is pointed out and psychotherapeutic attitude and action parameters are referred to achieve both the understanding of persons in those situations, and the correct clinical praxis towards them.

Experiencia comparativa do uso de etambutol e pirazinamida na fase de ataque do tratamento de curta duracao da tuberculose pulmonar. / Comparative study using ethambutol and pyrazinamide in initial intensive therapy of the pulmonary tuberculosis short term therapy

Com o objetivo de comparar a eficacia e eficiencia do etambutol e da pirazinamida e avaliar o real papel da "terceira" droga na fase de ataque do tratamento de curta duracao da tuberculose pulmonar, estudaram-se 151 pacientes portadores desta doenca. Todos os doentes foram comprovados por cultura de escarro positiva para o Mycobacterium tuberculosis e divididos em tres grupos, sendo um primeiro (49 pacientes) com uso de rifampicina (600 mg/dia) e isoniazida (400 mg/dia) por um periodo de seis meses, e outros dois em que se acrescentava nos dois meses iniciais ou o etambutol com 1.200 mg/dia (53 pacientes) ou a pirazinamida com 2.000 mg/dia (49 pacientes). A avaliacao final dos resultados terapeuticos e as recidivas apos o tratamento nao mostrou diferencas significativas entre os tres grupos estudados. Estes resultados nao revelam diferencas entre o etambutol e a pirazinamida e demonstraram a irrelevancia da "terceira" droga em esquemas onde a rifampicina e a isoniazida permanecem na fase de manutencao