Central neurodegeneration in Kennedy's disease accompanies peripheral motor dysfunction.

Spinal and bulbar muscular atrophy (SBMA), or Kennedy's disease (KD), is a rare hereditary neuromuscular disorder demonstrating commonalities with amyotrophic lateral sclerosis (ALS). The current study aimed to define functional and central nervous system abnormalities associated with SBMA pathology, their interaction, and to identify novel clinical markers for quantifying disease activity. 27 study participants (12 SBMA; 8 ALS; 7 Control) were recruited. SBMA patients underwent comprehensive motor and sensory functional assessments, and neurophysiological testing. All participants underwent whole-brain structural and diffusion MRI. SBMA patients demonstrated marked peripheral motor and sensory abnormalities across clinical assessments. Increased abnormalities on neurological examination were significantly associated with increased disease duration in SBMA patients (R2 = 0.85, p < 0.01). Widespread juxtacortical axonal degeneration of corticospinal white matter tracts were detected in SBMA patients (premotor; motor; somatosensory; p < 0.05), relative to controls. Increased axial diffusivity was significantly correlated with total neuropathy score in SBMA patients across left premotor (R2 = 0.59, p < 0.01), motor (R2 = 0.63, p < 0.01), and somatosensory (R2 = 0.61, p < 0.01) tracts. The present series has identified involvement of motor and sensory brain regions in SBMA, associated with disease duration and increasing severity of peripheral neuropathy. Quantification of annualized brain MRI together with Total Neuropathy Score may represent a novel approach for clinical monitoring.

A multidisciplinary approach on music induced-analgesia differentiated by socio-cultural background in healthy volunteers (MOSART): A cross-over randomized controlled trial protocol.

Background: Integrating music into pain treatment demonstrates significant benefits, effectively reducing subjective pain levels and perioperative opioid requirements. Currently, the relationship between the impact of specific types of music and listeners' socio-cultural background is still unclear. This is especially relevant given that sociological research indicates that these factors can have a notable influence on music preference and perception. Current evidence suggests that individuals who choose their own music may experience greater benefits. However, additional research is needed to comprehensively grasp whether the effect of (preferred) music on pain endurance remains consistent across different socio-cultural backgrounds. Methods: In this study, a collaborative effort between medical and sociological researchers aims to investigate music-induced analgesia differentiated by socio-cultural background in healthy volunteers. Participants (n = 84) will listen to self-, and researcher-chosen music and a podcast as a control condition in a cross-over study design. The primary outcome of this study is pain endurance measured by electric stimuli of increasing intensity. Detailed sociological validated questionnaires will be utilized. Considering the notable influence of educational level on music taste formation found in previous research and its crucial role as a source of socio-cultural differentiation, participants will be stratified based on their level of education. Discussion: This experimental study represents one of the first efforts to gain a socio-culturally differentiated understanding of the therapeutic potential of music. Consequently, this could pave the way to purposefully and inclusively implement personalized music in healthcare settings.

Sire: An interoperability engine for prototyping algorithms and exchanging information between molecular simulation programs.

Sire is a Python/C++ library that is used both to prototype new algorithms and as an interoperability engine for exchanging information between molecular simulation programs. It provides a collection of file parsers and information converters that together make it easier to combine and leverage the functionality of many other programs and libraries. This empowers researchers to use sire to write a single script that can, for example, load a molecule from a PDBx/mmCIF file via Gemmi, perform SMARTS searches via RDKit, parameterize molecules using BioSimSpace, run GPU-accelerated molecular dynamics via OpenMM, and then display the resulting dynamics trajectory in a NGLView Jupyter notebook 3D molecular viewer. This functionality is built on by BioSimSpace, which uses sire's molecular information engine to interconvert with programs such as GROMACS, NAMD, Amber, and AmberTools for automated molecular parameterization and the running of molecular dynamics, metadynamics, and alchemical free energy workflows. Sire comes complete with a powerful molecular information search engine, plus trajectory loading and editing, analysis, and energy evaluation engines. This, when combined with an in-built computer algebra system, gives substantial flexibility to researchers to load, search for, edit, and combine molecular information from multiple sources and use that to drive novel algorithms by combining functionality from other programs. Sire is open source (GPL3) and is available via conda and at a free Jupyter notebook server at https://try.openbiosim.org. Sire is supported by the not-for-profit OpenBioSim community interest company.

The MATRICS consensus cognitive battery for the assessment of cognitive impairment in schizotypal personality disorder.

Cognitive deficits are a core impairment across the range of schizophrenia (SZ) spectrum disorders, including schizotypal personality disorder (SPD). The MATRICS Consensus Cognitive Battery (MCCB) was developed to be a robust, specific, and valid cognitive assessment battery to assess cognition in clinical trials for treating cognitive impairments in SZ. Despite the similarity of cognitive impairments shown in SPD and SZ and the clear relevance of uniform assessment across a diagnostic spectrum, the MCCB has yet to be validated in SPD. As such, this is the first study to evaluate the sensitivity of the MCCB for the assessment of cognitive function in individuals with SPD. Participants were 30 individuals with SPD and 54 healthy controls (HC) assessed with the MCCB and supplemental neurocognitive assessments (Trails B, DOT test, Paced Auditory Serial Addition Test (PASAT), AX Continuous Performance Task (AX-CPT), and N-back). Individuals with SPD performed worse than HC participants on all MCCB subtests, as well as on converging supplemental tasks including Trails B, DOT test, PASAT, AX-CPT, and N-back. These results indicate that the MCCB was sensitive to cognitive impairment in SPD compared to controls. SPD participants demonstrate impairments similar to data of SZ participants within the literature, although to a slightly lesser degree of severity. Taken together, these results highlight the generalizability of using the MCCB across SZ spectrum diagnostic groups to assess cognition. Such findings allow for further comparison across disorders, greater understanding of the cognitive characteristics in the spectrum, and use of uniform assessment within cognitive intervention research.

Training in Cognitive Reappraisal Normalizes Whole-Brain Indices of Emotion Regulation in Borderline Personality Disorder.

BACKGROUND: Borderline personality disorder (BPD) is the prototypical disorder of emotion dysregulation. We have previously shown that patients with BPD are impaired in their capacity to engage cognitive reappraisal, a frequently employed adaptive emotion regulation strategy. METHODS: Here, we report on the efficacy of longitudinal training in cognitive reappraisal to enhance emotion regulation in patients with BPD. Specifically, the training targeted psychological distancing, a reappraisal tactic whereby negative stimuli are viewed dispassionately as though experienced by an objective, impartial observer. At each of 5 sessions over 2 weeks, 22 participants with BPD (14 female) and 22 healthy control participants (13 female) received training in psychological distancing and then completed a widely used picture-based reappraisal task. Self-reported negative affect ratings and functional magnetic resonance imaging data were acquired at the first and fifth sessions. In addition to behavioral analyses, we performed whole-brain pattern expression analyses using independently defined patterns for negative affect and cognitive reappraisal implementation for each session. RESULTS: Patients with BPD showed a decrease in negative affect pattern expression following reappraisal training, reflecting a normalization in neural activity. However, they did not show significant change in behavioral self-reports. CONCLUSIONS: To our knowledge, this study represents the first longitudinal functional magnetic resonance imaging examination of task-based cognitive reappraisal training. Using a brief, proof-of-concept design, the results suggest a potential role for reappraisal training in the treatment of patients with BPD.

Cold-water coral energy reserves and calcification in contrasting fjord environments.

The relationship between energy reserves of cold-water corals (CWCs) and their physiological performance remains largely unknown. In addition, it is poorly understood how the energy allocation to different metabolic processes might change with projected decreasing food supply to the deep sea in the future. This study explores the temporal and spatial variations of total energy reserves (proteins, carbohydrates and lipids) of the CWC Desmophyllum dianthus and their correlation with its calcification rate. We took advantage of distinct horizontal and vertical physico-chemical gradients in Comau Fjord (Chile) and examined the changes in energy reserves over one year in an in situ reciprocal transplantation experiment (20 m vs. 300 m and fjord head vs. mouth). Total energy reserves correlated positively with calcification rates. The fast-growing deep corals had higher and less variable energy reserves, while the slower-growing shallow corals showed pronounced seasonal changes in energy reserves. Novel deep corals (transplanted from shallow) were able to quickly increase both their calcification rates and energy reserves to similar levels as native deep corals. Our study shows the importance of energy reserves in sustaining CWC growth in spite of aragonite undersaturated conditions (deep corals) in the present, and potentially also future ocean.

Postconcussive Symptoms After Early Childhood Concussion.

Importance: Research on postconcussive symptoms (PCS) following early childhood concussion has been hindered by a lack of measures suitable for this age group, resulting in a limited understanding of their evolution in young children. Objective: To document PCS in the first 3 months after early childhood concussion using a developmentally appropriate measure. Design, Setting, and Participants: This cohort study used data collected at 3 Canadian and 1 US urban pediatric emergency departments (EDs) and 8 Canadian daycares from December 2018 to December 2022 as part of the Kids' Outcomes and Long-Term Abilities (KOALA) project, a prospective, multicenter, longitudinal cohort study. Participants included children aged 6 to 72 months with early childhood concussion or orthopedic injury (OI) or uninjured children from the community to serve as controls. Data were analyzed from March 2023 to January 2024. Exposure: Concussion sustained between ages 6 and 72 months. Main Outcomes and Measures: Primary outcomes were cognitive, physical, behavioral and total PCS assessed prior to injury (retrospectively), acutely (within 48 hours), and at 10 days, 1 month, and 3 months after injury or recruitment through caregiver observations using the Report of Early Childhood Traumatic Injury Observations & Symptoms inventory. Group comparisons were analyzed using ordinal regression models. Results: The study included 303 children (mean [SD] age, 35.8 [20.2] months; 152 [50.2%] male). Of these, 174 children had a concussion (mean [SD] age, 33.3 [19.9] months), 60 children had an OI (mean [SD] age, 38.4 [19.8] months) and 69 children were uninjured controls (mean [SD] age, 39.7 [20.8] months). No meaningful differences were found between the concussion and comparison groups in retrospective preinjury PCS. Significant group differences were found for total PCS at the initial ED visit (concussion vs OI: odds ratio [OR], 4.33 [95% CI, 2.44-7.69]; concussion vs control: OR, 7.28 [95% CI, 3.80-13.93]), 10 days (concussion vs OI: OR, 4.44 [95% CI, 2.17-9.06]; concussion vs control: OR, 5.94 [95% CI, 3.22-10.94]), 1 month (concussion vs OI: OR, 2.70 [95% CI, 1.56-4.68]; concussion vs control: OR, 4.32 [95% CI, 2.36-7.92]), and 3 months (concussion vs OI: OR, 2.61 [95% CI, 1.30-5.25]; concussion vs control: OR, 2.40 [95% CI, 1.36-4.24]). Significant group differences were also found for domain-level scores (cognitive, physical, behavioral) at various time points. Conclusions and Relevance: In this early childhood cohort study, concussion was associated with more PCS than OIs or typical development up to 3 months after injury. Given the limited verbal and cognitive abilities typical of early childhood, using developmentally appropriate manifestations and behaviors is a valuable way of tracking PCS and could aid in concussion diagnosis in young children.

Benchmarking Active Learning Protocols for Ligand-Binding Affinity Prediction.

Active learning (AL) has become a powerful tool in computational drug discovery, enabling the identification of top binders from vast molecular libraries. To design a robust AL protocol, it is important to understand the influence of AL parameters, as well as the features of the data sets on the outcomes. We use four affinity data sets for different targets (TYK2, USP7, D2R, Mpro) to systematically evaluate the performance of machine learning models [Gaussian process (GP) model and Chemprop model], sample selection protocols, and the batch size based on metrics describing the overall predictive power of the model (R2, Spearman rank, root-mean-square error) as well as the accurate identification of top 2%/5% binders (Recall, F1 score). Both models have a comparable Recall of top binders on large data sets, but the GP model surpasses the Chemprop model when training data are sparse. A larger initial batch size, especially on diverse data sets, increased the Recall of both models as well as overall correlation metrics. However, for subsequent cycles, smaller batch sizes of 20 or 30 compounds proved to be desirable. Furthermore, adding artificial Gaussian noise to the data up to a certain threshold still allowed the model to identify clusters with top-scoring compounds. However, excessive noise (<1σ) did impact the model's predictive and exploitative capabilities.

Phase I study of peposertib and avelumab with or without palliative radiotherapy in patients with advanced solid tumors.

INTRODUCTION: We report results from a phase I, three-part, dose-escalation study of peposertib, a DNA-dependent protein kinase inhibitor, in combination with avelumab, an immune checkpoint inhibitor, with or without radiotherapy in patients with advanced solid tumors. MATERIALS AND METHODS: Peposertib 100-400 mg twice daily (b.i.d.) or 100-250 mg once daily (q.d.) was administered in combination with avelumab 800 mg every 2 weeks in Part A or avelumab plus radiotherapy (3 Gy/fraction × 10 days) in Part B. Part FE assessed the effect of food on the pharmacokinetics of peposertib plus avelumab. The primary endpoint in Parts A and B was dose-limiting toxicity (DLT). Secondary endpoints were safety, best overall response per RECIST version 1.1, and pharmacokinetics. The recommended phase II dose (RP2D) and maximum tolerated dose (MTD) were determined in Parts A and B. RESULTS: In Part A, peposertib doses administered were 100 mg (n = 4), 200 mg (n = 11), 250 mg (n = 4), 300 mg (n = 6), and 400 mg (n = 4) b.i.d. Of DLT-evaluable patients, one each had DLT at the 250-mg and 300-mg dose levels and three had DLT at the 400-mg b.i.d. dose level. In Part B, peposertib doses administered were 100 mg (n = 3), 150 mg (n = 3), 200 mg (n = 4), and 250 mg (n = 9) q.d.; no DLT was reported in evaluable patients. Peposertib 200 mg b.i.d. plus avelumab and peposertib 250 mg q.d. plus avelumab and radiotherapy were declared as the RP2D/MTD. No objective responses were observed in Part A or B; one patient had a partial response in Part FE. Peposertib exposure was generally dose proportional. CONCLUSIONS: Peposertib doses up to 200 mg b.i.d. in combination with avelumab and up to 250 mg q.d. in combination with avelumab and radiotherapy were tolerable in patients with advanced solid tumors; however, antitumor activity was limited. GOV IDENTIFIER: NCT03724890.

Axonal excitability as an early biomarker of nerve involvement in hereditary transthyretin amyloidosis.

OBJECTIVES: The treatment of hereditary transthyretin amyloidosis polyneuropathy (ATTRv-PN) has been revolutionised by genetic therapies, with dramatic improvements in patient outcomes. Whilst the optimal timing of treatment initiation remains unknown, early treatment is desirable. Consequently, the aim of the study was to develop biomarkers of early nerve dysfunction in ATTRv-PN. METHODS: Ulnar motor and sensory axonal excitability studies were prospectively undertaken on 22 patients with pathogenic hereditary transthyretin amyloid (ATTRv) gene variants, 12 with large fibre neuropathy (LF+) and 10 without (LF-), with results compared to age- and sex-matched healthy controls. RESULTS: In motor axons we identified a continuum of change from healthy controls, to LF- and LF+ ATTRv with progressive reduction in hyperpolarising threshold electrotonus (TEh40(10-20 ms): p = 0.04, TEh40(20-40 ms): p = 0.01 and TEh40(90-10 ms): p = 0.01), suggestive of membrane depolarisation. In sensory axons lower levels of subexcitability were observed on single (SubEx) and double pulse (SubEx2) recovery cycle testing in LF+ (SubEx: p = 0.015, SubEx2: p = 0.015, RC(2-1): p = 0.04) suggesting reduced nodal slow potassium conductance, which promotes sensory hyperexcitability, paraesthesia and pain. There were no differences in sensory or motor excitability parameters when comparing different ATTRv variants. CONCLUSIONS: These progressive changes seen across the disease spectrum in ATTRv-PN suggest that axonal excitability has utility to identify early and progressive nerve dysfunction in ATTRv, regardless of genotype. SIGNIFICANCE: Axonal excitability is a promising early biomarker of nerve dysfunction in ATTRv-PN.

Serum neurofilament light chain in hereditary transthyretin amyloidosis: validation in real-life practice.

BACKGROUND: Neurofilament light chain (NfL) has emerged as a sensitive biomarker in hereditary transthyretin amyloid polyneuropathy (ATTRv-PN). We hypothesise that NfL can identify conversion of gene carriers to symptomatic disease, and guide treatment approaches. METHODS: Serum NfL concentration was measured longitudinally (2015-2022) in 59 presymptomatic and symptomatic ATTR variant carriers. Correlations between NfL and demographics, biochemistry and staging scores were performed as well as longitudinal changes pre- and post-treatment, and in asymptomatic and symptomatic cohorts. Receiver-operating analyses were performed to determine cut-off values. RESULTS: NfL levels correlated with examination scores (CMTNS, NIS and MRC; all p < .01) and increased with disease severity (PND and FAP; all p < .05). NfL was higher in symptomatic and sensorimotor converters, than asymptomatic or sensory converters irrespective of time (all p < .001). Symptomatic or sensorimotor converters were discriminated from asymptomatic patients by NfL concentrations >64.5 pg/ml (sensitivity= 91.9%, specificity = 88.5%), whereas asymptomatic patients could only be discriminated from sensory or sensorimotor converters or symptomatic individuals by a NfL concentration >88.9 pg/ml (sensitivity = 62.9%, specificity = 96.2%) However, an NfL increment of 17% over 6 months could discriminate asymptomatic from sensory or sensorimotor converters (sensitivity = 88.9%, specificity = 80.0%). NfL reduced with treatment by 36%/year and correlated with TTR suppression (r = 0.64, p = .008). CONCLUSIONS: This data validates the use of serum NfL to identify conversion to symptomatic disease in ATTRv-PN. NfL levels can guide assessment of disease progression and response to therapies.

Markov State Models: To Optimize or Not to Optimize.

Markov state models (MSM) are a popular statistical method for analyzing the conformational dynamics of proteins including protein folding. With all statistical and machine learning (ML) models, choices must be made about the modeling pipeline that cannot be directly learned from the data. These choices, or hyperparameters, are often evaluated by expert judgment or, in the case of MSMs, by maximizing variational scores such as the VAMP-2 score. Modern ML and statistical pipelines often use automatic hyperparameter selection techniques ranging from the simple, choosing the best score from a random selection of hyperparameters, to the complex, optimization via, e.g., Bayesian optimization. In this work, we ask whether it is possible to automatically select MSM models this way by estimating and analyzing over 16,000,000 observations from over 280,000 estimated MSMs. We find that differences in hyperparameters can change the physical interpretation of the optimization objective, making automatic selection difficult. In addition, we find that enforcing conditions of equilibrium in the VAMP scores can result in inconsistent model selection. However, other parameters that specify the VAMP-2 score (lag time and number of relaxation processes scored) have only a negligible influence on model selection. We suggest that model observables and variational scores should be only a guide to model selection and that a full investigation of the MSM properties should be undertaken when selecting hyperparameters.

Detection, purification and characterization of a lectin from freshwater green algae Spirogyra spp

ABSTRACT Freshwater algae are rich sources of structurally biologically active metabolites, such as fatty acids, steroids, carotenoids and polysaccharides. Among these metabolites, lectins stand out. Lectins are proteins or glycoproteins of non-immune origin which bind to carbohydrates or glycoconjugates, without changing ligand structure. Many studies have reported on the use of Spirogyra spp. as effective bioindicators of heavy metals; however, reports on Spirogyra molecular bioprospecting are quite limited. Therefore, this study aimed to detect, isolate, purify and characterize a lectin present in the freshwater green algae Spirogyra. Presence of the lectin protein in the extract was detected by hemagglutination assays. Subsequently, the protein extract was subjected to a sugar inhibition assay to identify the lectin-specific carbohydrate. Following this, the extract was applied to a guar gum column to afford the pure lectin. The lectin was inhibited by N-acetyl-glucosamine and N-acetyl-beta-D-mannose, but more strongly by D-galactose. The apparent molecular mass of the purified lectin was evaluated by Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE). Electrophoretic analysis revealed a single protein band with an apparent molecular mass of 56 kDa. Thus, it could be concluded that a lectin was purified from Spirogyra spp.

Effects of fasting and refeeding on the metabolic functions of the turtle Kinosternon scorpioides (Linnaeus, 1766) raised in captivity / Efeitos do jejum e da realimentação sobre as funções metabólicas da tartaruga Kinosternon scorpioides (Linnaeus, 1766) criada em cativeiro

The metabolic responses of adult and young freshwater Kinosternon scorpioides turtles raised in captivity were evaluated. Two experiments were performed: a) blood metabolite changes caused by food deprivation, and b) liver and muscle glycogen and total lipid differences after fasting and refeeding. Blood glucose concentration of young animals was susceptible to food deprivation. In both groups this metabolite decreased after 30 days of fasting. Feeding for 15 days did not recover blood glucose. Total seric proteins were not affected by food deprivation. Fasting decreased blood urea nitrogen and the highest difference was found around 30 days. Uric acid increased in young animals after 60 days of fasting. Triacylglicerol decreased after 15 days of fasting and refeeding for 15 days recovered the pre-fasting levels. Free fatty acid plasma tended to increase around 15 days of fasting. Liver glycogen decreased at day 15 of fasting, being stable thereafter while muscle glycogen decreased at a slower rate. Total liver lipid stabilized after 30 days and then decreased 70% after 60 days of fasting. Muscle lipids remained stable throughout fasting. It could be concluded that fasting of Kinosternon scorpioides led to metabolic adaptations similar to the one reported from reptiles and fish.

Neste trabalho foi avaliada as respostas metabólicas da tartaruga Kinosternon scorpioides criada em cativeiro, nas fases, adultos e jovens nos estados: alimentado, jejuado e realimentado. O estudo compreendeu dois experimentos: (a) mudanças metabólicas no sangue causadas por privação alimentar e realimentação e (b) diferenças nas concentrações de glicogênio e lipídeos totais no fígado e no músculo após jejum e realimentação. No experimento dos animais jovens a concentração de glicose no sangue apresentou mudanças significativas. Entretanto, nos dois experimentos esse metabólito reduziu significativamente aos 30 dias de jejum. Realimentados por um período de 15 dias foi observado que a concentração de glicose não recuperou os níveis de pré-jejum. Concentração de glicose no sangue de animais jovens foi mais suscetível à privação de alimentos. Em ambos os grupos os metabólitos analisados decresceu após 30 dias de jejum. Retomando a alimentação por 15 dias foi observado que a concentração de glicose não recuperou. As concentrações de proteínas séricas totais não foram afetadas pela privação alimentar. O jejum decresceu a concentração de uréia no sangue e a maior diferença ocorreu aos 30 dias. O ácido úrico decresceu nos animais jovens após 60 dias de jejum. O triacilglicerol diminuiu após 15 dias de jejum e a realimentação por 15 dias recuperou os níveis de pré-jejum. O glicogênio hepático diminuiu aos 15 dias de jejum, e estabilizou a partir daí, enquanto o glicogênio muscular diminuiu a um ritmo mais lento. O lipídio total hepático total se manteve estável até os 30 dias de jejum, diminuindo até 70% aos 60 dias de jejum. E, em seguida, diminuiu 70% após 60 dias de jejum. Os lipídeos musculares permaneceram estáveis durante o jejum. Conclui-se que o jejum na espécie Kinosternon scorpioides apresentou adaptações metabólicas semelhantes aos relatados para outros répteis e peixes.

Morphological aspects of the ovaries of turtle Kinosternon scorpioides raised in captivity / Aspectos morfológicos dos ovários da tartaruga Kinosternon scorpioides criada em cativeiro

The swear turtle "jurará" (Kinosternon scorpioides) is a mud turtle of the Amazon region exposed to disordering capture in the rural areas of Maranhão, Brazil. Despite its popularity in these areas, little meaningful information regarding the reproductive morphology is currently available, fact that impedes the adoption of policies for preservation of the species. To obtain more information, we studied the ovarian morphology adult jurará females kept in captivity by morphological and morphometric analysis in the dry and rainy season. The results revealed that all females were sexually mature and were in a vitellogenic period. The ovaries are two irregular structures composed by follicles in different stages of development (primary, secondary and tertiary) scattered in a stroma of loose connective highly vascularized tissue. The ovary weight was 6.25±4.23g and 2.27±1.42g, for the right and left one respectively. The gonadosomatic indexes were 2.06% for the dry season and 1.79% for the rainy season. The average of the follicles was 29.83 units per ovary. Microscopically, the mature ovaries revealed a basal layer composed by four cellular layers: the inner and outer theca, stratum granulosum with perivitelline membrane and zona radiata with vitelline membrane. No significant differences were observed in the ovaries either in the dry or wet period.

O jurará (Kinosternon scorpioides) é um cágado da Região Amazônica que sofre com as capturas desordenadas nos interiores maranhenses e que apesar da sua popularidade nessas áreas, os dados relacionados à morfologia reprodutiva ainda são poucos esclarecedores, o que dificulta a adoção de medidas para preservação da espécie. Desta forma, caracterizou-se morfologicamente os ovários de fêmeas adultas de jurara oriundas de cativeiro através da análise morfológica e morfométrica em dois períodos do ano, seco e o chuvoso. Os resultados comprovaram que todas as fêmeas eram maduras sexualmente e se encontravam em período vitelogênico. Os ovários são duas estruturas irregulares constituídas por diversos folículos em desenvolvimento (primários, secundários e terciários) sobre um estroma de tecido conjuntivo frouxo ricamente vascularizado, com média de peso do direito e esquerdo respectivamente de 6,25±4,23g and 2,27±1,42g. Índices gonadossomáticos de 2,06% para o período seco e de 1,79% para o chuvoso. Média de folículos observados de 29,83 unidades por ovário. Histologicamente, os ovários maduros possuíam camada basal composta por quatro camadas celulares: as tecas externa e interna, o estrato granuloso com membrana perivitelínica e a zona radiata com membrana vitelínica. Não foram observadas diferenças significativas dos ovários entre os dois períodos estudados.

The occurrence of Phlebotomines (Diptera psychodidae) in a Leshmaniasis endemic area / Ocorrência de Flebotomíneos (Diptera psychodidae) em área endêmica de Leshmanioses

Objective: we describe the occurrence of phlebotomines in urban areas of Caxias, Maranhão state, whereautochthonous cases of visceral leishmaniasis (kala azar) and tegumentary leishmaniasis were reported.Method: The phlebotomines were captured in 40 districts in the periods January to December 2001, May toNovember 2004, and January to November 2005 using CDC light traps installed from 6 pm to 6 am in thehouses and peridomiciles. Results: a total of 28,336 specimens (21,006 males and 7,330 females) from 11species were collected. Ten of the species belonged to the genus Lutzomyia and one to the genus Brumptomyia.The most abundant species was Lutzomyia longipalpis (93.7%), which was also the most widely distributed inthe city, followed by L. whitmani (5.2%). Conclusions: this pattern of abundance indicates that these were thetwo species best adapted to the urban environment, and they were thus incriminated in the transmission of thecases of kala azar (Lutzomyia longipalpis) and tegumentary leishmaniasis (L. whitmani) reported in Caxias. Theother species were considered occasional or rare visitors to the areas

Objetivo: descreve-se a ocorrência de flebotomíneos em áreas urbanas com notificação de casosautóctones de leishmaniose visceral (calazar) e leishmaniose tegumentar. Método: nos períodos dejaneiro a dezembro de 2001, maio a novembro de 2004 e janeiro a novembro de 2005 foram feitosinquéritos entomológicos de flebotomíneos em 40 bairros da cidade de Caxias, estado do Maranhão.Os espécimes foram coletados utilizando-se armadilhas luminosas do tipo CDC instaladas das 18 às6 horas, no peri e intradomicílio. Resultados: foram coletados 28.336 espécimes (machos: 21.006;fêmeas: 7.330), de 11 espécies, sendo 10 pertencentes ao gênero Lutzomyia e 1 ao gêneroBrumptomyia. A espécie mais abundante foi L. longipalpis (93,7%) e também a mais bemdistribuída dentro da cidade, seguida por L. whitmani (5,2%). Conclusões: por esse padrão deabundância, verifica-se que essas duas espécies são as mais bem adaptadas ao ambiente urbano,sendo atraídas principalmente por galinheiros, chiqueiros e estábulos, além dos domicílioshumanos. As demais espécies foram consideradas visitantes ocasionais e raras nas áreas. Os casosde calazar e leishmaniose tegumentar notificados em Caxias são atribuídos a essas duas espécies,respectivamente.

Ultrasonographic and radiographic determination of egg development of jurarás (Kinosternon scorpioides) in captivity / Determinação ultrassonográfica e radiográfica do desenvolvimento de ovos de jurarás em cativeiro

Kinosternon scorpioides (Linnaeus, 1766), with its common name of jurará, is a quite variable species of turtles, and many different names have been applied to populations throughout its range. Currently, however, four subspecies are considered valid as K. scorpioides arises from southern Panama over most of northern South America and is found in Ecuador, northern Peru, southern Bolivia, northern Argentina, eastern Guyana and Brazil. Thus, an ultrasonographic and radiographic study was performed in order to describe the morphology and development of eggs of 20 female jurará mud turtles K. scorpioides, from September 2005 to August 2006. In the first month, the ovarian cycle was characterized by absence of vitellogenic follicles, atresic follicles or oviduct eggs. From October 2005 to March 2006 on, ultrasonographic scanning allowed to establish the growing vitellogenic follicles. Vitellogenic follicles were observed with spherical to ovoid shapes, with a surrounding echogenic yolk, a nonechogenic albumin layer, and a high echogenic shell. The oviduct eggs were identified by radiography just 180 days after beginning the experiment, when the shell became enough mineralized to impress the radiographic film. This experiment allowed to obtain by means of the 7.5 MHz linear probe images with adequate resolution and penetration for visualization of follicles. Successive ultrasonographic examinations of 20 K. scorpioides females allowed to access initial stages of vitellogenic follicles and oviduct eggs, and radiographic examination revealed to be an easy technique to assess oviduct eggs and to allow evaluation of egg development in jurarás, from 6 months on.

A tartaruga Kinosternon scorpioides (Linnaeus, 1766), com nome popular de jurará, é uma espécie bastante variável, e muitos nomes diferentes são atribuídos às suas populações, de acordo com sua localização geográfica. Atualmente, quatro subespécies foram validadas como K. scorpioides surgindo desde o extremo Sul do Panamá e norte da América do Sul, podendo ser encontradas ainda no Equador, no norte do Peru, sul da Bolívia, norte da Argentina, leste da Guiana e no Brasil. Desde modo, foi realizado um estudo ultrassonográfico e radiológico, a fim de descrever a morfologia e o desenvolvimento dos ovos de K. scorpioides em cativeiro, utilizando-se 20 fêmeas, no período de setembro de 2005 a agosto de 2006. No primeiro mês, o ciclo ovariano foi caracterizado pela ausência de folículos vitelogênicos, atrésicos ou presença de ovos em ovidutos. De outubro de 2005 a março de 2006 a varredura ultrassonográfica permitiu determinar o crescimento vitelogênico dos folículos, os quais foram observados com um formato que variou de ovóide a esférico, envolvidos por um conteúdo ecogênico, uma camada não-ecogência de albumina e uma casca de elevada ecogenicidade. Ovos presentes em ovidutos foram identificados por radiografias apenas 180 dias após início do experimento, quando a casca tornou-se suficientemente mineralizada para impressionar o filme radiográfico. Um transdutor linear de 7,5 MHz promoveu imagens com resolução e penetração adequada para visibilização de folículos. Exames ultrassonográficos sucessivos em fêmeas K. scorpioides permitiram determinar os estágios iniciais de desenvolvimento de folículos vitelogênicos e o exame radiográfico mostrou-se como técnica simples para avaliar a presença de ovos em ovidutos, permitindo fazer inferências sobre desenvolvimento de ovos em jurarás, a partir dos 6 meses de pós-observação por ultrassonografia.

Cell proliferation and interferon-gamma response to recombinant MBP-3, NarL, MT-10.3, and 16kDa Mycobacterium tuberculosis antigens in Brazilian tuberculosis patients

Human pulmonary tuberculosis (TB) is a worldwide public health problem. In resistant individuals, control of the infection mainly requires development of a Th1 cell immune response with production of cytokines, of which interferon-gamma (IFN-gamma)plays an important role. Several antigens from Mycobacterium tuberculosis complex has been described for use in vaccine development or for diagnostic purposes, however little evaluation has been done in endemic area for TB. The proliferative and IFN-gamma human T cell immune responses, to four recombinant proteins (MBP-3, NarL, MT-10.3, 16 kDa) and PPD, of 38 Brazilian TB patients (6 untreated and 32 treated) and 67 controls (38 positive and 29 negative tuberculin skin test - TST) were compared. The highest reactivity mean rate was obtained with PPD followed by 16 kDa in TB patients. While most of the patients (87 percent) and controls (> 64 percent) respond to the PPD, 16kDa was more specifically recognized (> 21 percent) although less sensitive (54 percent). When TB patients were divided according to treatment status, opposite to PPD, higher average level of IFN-gamma was induced by 16kDa in untreated (505 pg/ml) compared to treated TB patients and TST+ (269.8 pg/ml x 221.6pg/ml, respectively), although the difference was not significant. These data show that in contrast with the other recombinant proteins, the stimulatory potency of 16kDa to induce proliferative and INF-gamma response was more effective and is more recognized by active TB untreated patients, eliciting in control individuals a more selective immune response than PPD.