Photolysis of CH3CN Ices by Soft X-rays: Implications for the Chemistry of Astrophysical Ices at the Surroundings of X-ray Sources.

In this work, broad-band soft X-ray (6-2000 eV) was employed to irradiate frozen acetonitrile CH3CN, at the temperature 13 K, with different photon fluences up to 1.5 × 1018 photons cm-2. Here, acetonitrile is considered as a representative complex organic molecule (COM) present in astrophysical water-rich ices. The experiments were conduced at the Brazilian synchrotron facility (LNLS/CNPEM) employing infrared spectroscopy (FTIR) to monitor chemical changes induced by radiation. The effective destruction cross section of acetonitrile and effective formation cross section for daughter species formed inside the ice were obtained. The identified radiation products were HCN, CH4, H2CCNH, and CH3NC showing that fragmentation and rearrangement contribute to acetonitrile destruction. Chemical equilibrium and molecular abundances at this stage were determined, which also includes the abundance estimates of unknown molecules, produced but not directly detected, in the ice. The chemical equilibrium was reached at fluence around 1.5 × 1018 photons cm-2. Time scales for ices, at hypothetical snow line distances, to reach chemical equilibrium around compact objects, young stellar objects, and O/B stars and inside solar system were given. Among the obtained results are the time scales for reaching chemical equilibrium around different astronomical strong X-ray emitters, e.g., 14 days (for the Sun at 5 AU), 41 and 82 days (for O/B stars at 5 AU), 109-1011 years (for white dwarfs at 1 LY), 450 years (for Crab pulsar at 2.25 LY), around 107 years (for Vela pulsar at 2.25 LY), and 7.5 × 106 years (for Sagittarius A* at 3 LY).

Anti-parietal cell antibodies in patients with autoimmune thyroid diseases.

BACKGROUND: Autoimmune thyroid disease (ATD) patients may have a higher prevalence of anti-parietal cell antibodies (APCA) than normal population. OBJECTIVE: To study the prevalence of APCA in a cohort of ATD patients to know its association with patient's clinical profile and gastrointestinal complaints. METHODS: APCA was sought for by indirect immunofluorescence test in 243 ATD patients: 136 (55.9%) with Graves' disease and 107 (44.0%) with Hashimoto's thyroiditis. A structured questionnaire for gastrointestinal symptoms, previous history of thrombosis, arthralgia and other autoimmune diseases in the patients and their families was applied. Positive and negative APCA individuals were compared. Positive patients were invited to perform upper gastrointestinal endoscopy and biopsy of duodenum segments. Sera from 100 healthy individuals from the same geographic area were used as controls. RESULTS: APCA was present in 20.1% (49/243) of ATD patients: 21.3% (29/136) in the Graves' sample and 18.6% (20/107) in the Hashimoto's sample (p = 0.61). Patients with positive APCA had more anemia (p = 0.03; OR = 2.89; 95% CI = 1.03-8.07) and less heartburn (p = 0.01; OR = 0.4; 95% CI = 0.20-0.83). Among the group of 49 APCA-positive patients, 24 agreed with upper endoscopy and it was found that 54.1% had atrophic gastritis. CONCLUSIONS: There is a high prevalence of positive APCA in ATD patients. APCA are more common in those with anemia and less common in those with complaints of heartburn. Almost half of positive APCA patients had atrophic gastritis.

Selection of Annonaceae Species for the Control of Spodoptera frugiperda (Lepidoptera: Noctuidae) and Metabolic Profiling of Duguetia lanceolata Using Nuclear Magnetic Resonance Spectroscopy.

This study was performed to investigate the activity of 19 dichloromethane-soluble fractions obtained from the methanolic extracts of 10 Annonaceae species against the fall armyworm, Spodoptera frugiperda (J. E. Smith). The stem bark of Duguetia lanceolata A. St.-Hil. showed the highest insecticidal activity, with a median lethal time (LT50) of 61.4 h and a median lethal concentration (LC50) of 946.5 µg/ml of diet. The dichloromethane-soluble fractions from six D. lanceolata specimens were subjected to evaluation of their activities against S. frugiperda and metabolomic analysis using hydrogen (1H) nuclear magnetic resonance (NMR) spectroscopy. Although all of the samples affected S. frugiperda mortality, their insecticidal activities varied according to the sample used in the experiments. Using partial least squares regression of the results, the D. lanceolata specimens were grouped according to their metabolite profile and insecticidal activity. A detailed analysis via uni- and bidimensional NMR spectroscopy showed that the peaks in the 1H NMR spectra associated with increased insecticidal activity could be attributed to 2,4,5-trimethoxystyrene, which suggests that this substance is involved in the insecticidal activity of the stem bark fraction of D. lanceolata.

Lethal and Sublethal Impacts of Acaricides on Tamarixia radiata (Hemiptera: Eulophidae), an Important Ectoparasitoid of Diaphorina citri (Hemiptera: Liviidae).

The use of synthetic acaricides for management of pest mites may alter the efficacy of the ectoparasitoid Tamarixia radiata (Waterston) in biological control of Diaphorina citri Kuwayama, the vector of the bacteria associated with huanglongbing (HLB) in citrus orchards. We evaluated the toxicity of 16 acaricides that are recommended for the control of citrus-pest mites to T. radiata. Acrinathrin, bifenthrin, carbosulfan, and fenpropathrin caused high acute toxicity and were considered harmful (mortality >77%) to T. radiata. Abamectin, diflubenzuron, etoxazole, fenbutatin oxide, fenpyroximate, flufenoxuron, hexythiazox, propargite, spirodiclofen, and sulfur caused low acute toxicity and affected the parasitism rate and emergence rate of adults (F1 generation), and were considered slightly harmful to T. radiata. Dicofol and pyridaben did not affect the survival and action of the ectoparasitoid, and were considered harmless. In addition to its acute toxicity, carbosulfan caused mortality higher than 25% for >30 d after application, and was considered persistent. Acrinathrin, bifenthrin, fenpropathrin, fenpyroximate, propargite, and sulfur caused mortalities over 25% until 24 d after application and were considered moderately persistent; abamectin was slightly persistent, and fenbutatin oxide was short lived. Our results suggest that most acaricides used to control pest mites in citrus affect the density and efficacy of T. radiata in the biological control of D. citri. However, further evaluations are needed in order to determine the effect of these products on this ectoparasitoid under field conditions.

Prediction of potential novel microRNAs in soybean when in symbiosis.

MicroRNAs (miRNAs) are small molecules, noncoding proteins that are involved in many biological processes, especially in plants; among these processes is nodulation in the legume. Biological nitrogen fixation is a key process, with critical importance to the soybean crop. This study aimed to identify the potential of novel miRNAs to act during the root nodulation process. We utilized a set of transcripts that were differentially expressed in soybean roots 10 days after inoculation with Bradyrhizobium japonicum, which were obtained in a previous study, and performed a set of computational analyses that led us to select new miRNAs potentially involved in nodulation. Among these analyses, the set of transcripts were submitted to an in silico annotation of noncoding RNAs, including a search of similarity against miRNA public databases, ab initio tools for miRNA identification, structural search against miRNA families, prediction of the secondary structure of miRNA precursors, and prediction of the sequences of mature miRNAs. Subsequently, we applied filter procedures based on miRNA selections described in the literature (e.g., free energy value). In the next step, a manual curation inspection of the annotation was performed and the top candidates were selected and used for prediction of potential target genes, which were later checked manually in the database of the soybean genome. This prediction led us to the identification of 9 potential new miRNAs; among these, 4 were conserved in other plants. Moreover, we predicted their target genes might play important roles in the regulation of nodulation.

Identifying health outcomes of pharmaceutical clinical services in patients with cancer: A systematic review.

BACKGROUND: Cancer is a major public health problem that imposes limitations on patients being treated. One of the strategies to improve health outcomes in cancer patients and promote the safety of their treatment is the provision of pharmaceutical clinical services (PCS). However, there is no evidence of health outcomes that are influenced by such services. OBJECTIVE: Identify the health outcomes influenced by PCS in cancer patients. METHODS: A systematic review was performed in the following databases: Cochrane Library, LILACS, PubMed, EMBASE, and Web of Science, and using the PRISMA Statement In addition to the search, we analyzed the references of systematic reviews and meta-analyses. The descriptors used were defined by the MeSH keywords "neoplasms," "pharmacists," and "pharmaceutical services". We analyzed the studies with an observational design published until March 2018 that used PCS and related them with the health outcomes. Two reviewers independently assessed titles, abstracts, and full texts according to the eligibility criteria, and then extracted data and assessed the methodological quality of the studies. RESULTS: A total of 658 articles were found in the initial search, of which eight met the inclusion criteria. Six studies evaluated clinical outcomes: four assessed adverse reactions, one identified six barriers that prevented patients' adherence to medication and solved three of these barriers, and two evaluated PCS related to drug-related problems (DRP) in identification and resolution. Four studies identified a humanistic outcome: two evaluated the quality of life of patients on cancer treatment associated with improvement of symptoms, two investigated pain, and two performed a patient satisfaction survey on PCS. This systematic review identified only one study with an economic outcome, addressing the reduction of medical expenses related to the treatment of neutropenia that affects cancer patients. Most of the studies showed good methodological quality. CONCLUSIONS: This systematic review identified health outcomes associated with PCS in cancer patients: clinical (adverse drug reaction, DRP resolution, adherence, and pain), humanistic (quality of life and satisfaction), and economic outcomes (reduction of treatment costs for cancer).

Maturation and harvest time of Ateleia glazioveana Baill. seeds.

Ateleia glazioveana Baill. is a pioneer, rustic and can be used for forest recovery. This work aimed to study the process of physiological maturation of this species. The research was carried out in the city of Alegre - ES, the trees were identified in the floral anthesis and accompanied during the filling of the fruits and development of the seeds until the complete maturation. The fruits were harvested at the following stages 7, 14, 21, 28, 35 and 42 days after anthesis, and characterized according to: morphometry, moisture, fresh and dry mass of fruits and seeds, germination, germination speed index, shoot and root length and dry mass of seedlings. The regression equations were adjusted for the main characteristics analyzed as a function of the harvest period. The point of physiological maturity of timbó occurred at 42 days after anthesis.

Recombinant human TSH increases the efficacy of a fixed activity of radioiodine for treatment of multinodular goitre.

CONTEXT: High doses of (131)I are usually needed in the treatment of multinodular goitre (MNG) for effective thyroid volume (TV) reduction. Recombinant human thyroid-stimulating hormone (rhTSH) is an adjuvant to enhance (131)I uptake, allowing a decrease in radiation activity and enhancing (131)I efficacy. OBJECTIVE: To evaluate whether rhTSH increases the efficacy of a fixed activity of (131)I for the treatment of MNG. DESIGN: Two-year, observational, placebo-controlled study. SETTING: Patients received 0.1 mg rhTSH (A), 0.005 mg rhTSH (B) or placebo (C). A fixed activity of 1.11 GBq of (131)I was administered 24 h after rhTSH or placebo. PATIENTS: A total of 28 outpatients (26 females and two males) with MNG. MEASUREMENTS: TSH, free T4, T3, thyroglobulin (Tg) and TV. RESULTS: Basal radioactive iodine uptake and TV values were comparable among all groups. After rhTSH or placebo, peak levels of TSH, free T4, T3 and Tg were higher in A than in B or in C (p < 0.05). Hyperthyroidism was observed in A (n = 2), B (n = 6) and C (n = 4). Thyroid enlargement was reported in A (n = 3) and B (n = 6). After 24 months, 10 patients developed hypothyroidism (four in A, three in B and three in C). TV reduction was similar between A and B (37.2 +/- 25.5% vs. 39.3 +/- 27.9%, p = 0.88), but different from the non-significant reduction in C (15.3 +/- 28.3%, p = 0.08). CONCLUSIONS: Followed by 1.11 GBq, a very low dose of 0.005 mg rhTSH was equally safe and effective as 0.1 mg rhTSH. Both doses increased the efficacy of radioiodine. Adverse events were mild, transient and readily treatable.

Effects of essential oils on Aedes aegypti larvae: alternatives to environmentally safe insecticides.

The essential oils from leaves of Hyptis fruticosa (Lamiaceae) Salzm., H. pectinata (Lamiaceae) Poit., and Lippia gracilis (Verbenaceae) HBK were investigated for their larvicidal activity against Aedes aegypti and analyzed by GC/MS. Fifty-nine compounds, representing 91.28-98.39% of the essential oils, have been identified. A standard solution was used to make 20 mL solutions ranging from 30 to 2000 ppm. Twenty larvae between third and fourth stages were added to the essential oil solution. A mortality count was conducted 24 h after treatment. Essential oils LC50 and their confidence limits at 95% probability were calculated by the methods of Reed-Muench and Pizzi, respectively. The essential oil of Lippia gracilis showed potent insecticidal effect against Aedes aegypti larvae, the vector of dengue fever. Carvacrol and caryophyllene oxide were the main responsible for the activity of L. gracilis and H. pectinata. Minor compounds are probably acting synergistically to achieve H. fruticosa activity.

Effects of Aqueous Extracts of Copaifera langsdorffii (Fabaceae) on the Growth and Reproduction of Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae).

Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae) is considered a pest of maize crops throughout the Western Hemisphere. We report on the effects of aqueous extracts of leaves and bark of Copaifera langsdorffii (Fabaceae) on the biology of S. frugiperda, as an alternative source of natural bioactive molecules for the sustainable management of this pest. Second instars were sprayed with aqueous extracts prepared with 5% (w/v) plant material and/or fed on an artificial diet containing extracts at a concentration equivalent to 0.25% (w/v) for 17 days. Both leaf and bark extracts of C. langsdorffii significantly reduced S. frugiperda food intake, feces, and larval weight and caused a delay in larval development. Additionally, C. langsdorffii-based extracts increased the oviposition period; induced morphological changes in the eggs, including deformation of the corium and malformation of the micropylar and aeropylar regions; and reduced egg viability. But, aqueous extracts of C. langsdorffii exhibited no negative effects on larval and pupal survival, duration of the pupal stage, survival of pupae, sex ratio, longevity, duration of pre-oviposition period, and female fecundity. Aqueous extracts of leaves and bark of C. langsdorffii are promising alternatives for the control of S. frugiperda in maize crops.

Ingestive behavior of Girolando heifers in integrated crop, livestock (ICL), and forestry (ICLF) systems / [Comportamento ingestivo de novilhas Girolando mantidas em sistemas de integração lavoura-pecuária (ILP) e lavoura-pecuária-floresta (ILPF]

Aiming to compare integrated crop, livestock (ICL) and forest (ICLF) systems in relation to ingestive behavior of dairy heifers, a 2 × 2 crossover trial was conducted with two periods and two systems. Eight Girolando (3/4holstein × 1/4 Gyr) heifers were evaluated in pasture of Xaraés palisade grass (Urochloa brizantha 'Xaraes' syn Brachiaria brizantha) managed with intermittent stocking. The ICLF systemhad eucalyptus trees planted in tiers with 65% crown cover. Ingestive behavior parameters were obtained using acoustic data collected with mP3 recorders for 48hours. Statistical analysis was performed using the mixed procedure of SAS, and means were compared using the Tukey-Kramer test at 5% significance. The dry mater intake (DMI), number of daily grazing sessions, and the duration of the grazing sessions did not differ (P<0.05) between systems. A higher (P<0.05) bite rate and total daily bites and lower (P<0.05) bite mass was observed in the ICLF system in relation to ICL. Heifers in shaded pasture change their ingestive behavior in comparison with those in full-sun pasture.(AU)

Com o objetivo de comparar sistemas de integração lavoura-pecuária (ILP) e lavoura-pecuária-floresta (ILPF) em relação ao comportamento ingestivo de novilhas leiteiras, conduziu-se um ensaio em delineamento crossover 2 × 2, com dois períodos e dois sistemas. Oito novilhas Girolando foram mantidas em pastagens de capim-xaraés (Urochloa brizantha 'Xaraes' syn Brachiaria brizantha) manejadas com lotação intermitente. No sistema ILPF, havia renques de eucalipto com 65% de cobertura de copa. O comportamento ingestivo foi avaliado pela análise de áudios coletados com gravadores de Mp3, durante 48 horas. As análises estatísticas foram realizadas utilizando-se Proc mixed SAS. As médias foram comparadas pelo teste Tukey-Kramer, ao nível de 5% de significância. A ingestão de matéria seca (IMS), o número de sessões de pastejo por dia e a duração das sessões de pastejo não diferiram (P<0,05) entre os sistemas. As maiores (P<0,05) médias de taxa de bocado e de número de bocados por dia e a menor (P<0,05) média de massa de bocado foram observadas no ILPF quando comparado ao ILP. Novilhas em pastagem sombreada alteram seu comportamento ingestivo quando comparadas àquelas que são mantidas em pastagem a pleno sol.(AU)

Prevalence of infection by Cryptosporidium spp. in calves and associated risk factors in Northeastern Brazil / [Prevalência da infecção por Cryptosporidium spp. e fatores de risco associados em bezerros do Nordeste do Brasil]

Cryptosporidium spp. are zoonotic protozoa, frequently associated with diarrhea in calves, which are responsible for important economic losses. The aim of this study was to assess the prevalence of infection by Cryptosporidium spp. and its associated risk factors among calves raised in a milk production region of Northeastern Brazil. Fecal samples (n = 385) were obtained from young animals (up to ten months old) and evaluated by means of centrifugal fecal sedimentation in formalin-ether followed by the modified Ziehl-Neelsen staining technique. In addition, Odds Ratio (OR) was calculated to evaluate associations between variables and infection by these protozoa. Out of all samples analyzed, 25.7% (99/385) scored positive for the presence of Cryptosporidium spp. Contact with other species (goat and sheep) (OR = 3.33; p = 0.000), use of a semi-intensive rearing system (OR = 1.70; p = 0.024) and absence of hygienic conditions (fecal contamination of food and water) (OR = 1.64; p = 0.029) were considered to be risk factors. Data herein reported shows that the implementation of hygienic-sanitary measures on the farms studied, it is imperative to reduce Cryptosporidium spp. infection and consequently the economic impact caused by this pathogen.(AU)

Cryptosporidium spp. são protozoários zoonóticos frequentemente associados à diarreia em bezerros e responsáveis por importantes perdas econômicas. O objetivo deste estudo foi avaliar a prevalência e os fatores de risco associados à infecção por Cryptosporidium spp. em bezerros de propriedades leiteiras no Nordeste do Brasil. Amostras fecais (n = 385) foram obtidas de animais jovens (até 10 meses de idade) e avaliadas por centrífugo-sedimentação em formol éter, seguida da técnica de coloração de Ziehl-Neelsen modificada. A Odds Ratio (OR) foi calculada para avaliar a associação entre variáveis e infecção pelos protozoários. De todas as amostras analisadas, 25,7% (99/385) apresentaram oocistos de Cryptosporidium spp. Contato com outras espécies (caprino e ovino) (OR = 3,33; p = 0,000), sistema semi-intensivo de criação (OR = 1,70; p = 0,024) e ausência de condições higiênicas (contaminação fecal do alimento e da água) (OR = 1,64; p = 0,029) foram considerados fatores de risco. Com base nos resultados, é imprescindível a adoção de medidas higiênico-sanitárias nas fazendas estudadas, a fim de reduzir infecção por Cryptosporidium spp. e o impacto econômico causado por esse patógeno.(AU)

Ectoparasites infesting animals living in close contact with human beings: a real trouble for One Health perspective? / [Ectoparasitos infestando animais que vivem em contato próximo com seres humanos: um problema real para a perspectiva Saúde Única?]

The number of domestic animals living with human beings is rapidly increasing in parallel with an enhanced risk of transmission of their parasites and the pathogens they might carry. The aim of this study was to assess the occurrence of hematophagous arthropods infesting domestic animals from Northeastern Brazil and to remark the implications of their occurrence on the epidemiology and control of selected veterinary and human diseases. From January 2017 to April 2019, ectoparasites infesting domestic cats, dogs and horses were collected for their respective hosts and identified. Overall, ectoparasites were sampled from 86 domestic animals, living in different anthropic settings. A total of 401 specimens (344 ticks and 57 fleas) were collected from different hosts [i.e., 10 (2.49%), 96 (23.94%) and 295 (73.57%) from cats, dogs and horses, respectively]. Two flea (i.e., Ctenocephalides canis and Ctenocephalides felis) and 5 tick species (i.e., Amblyomma ovale, Amblyomma sculptum, Dermacentor nitens, Rhipicephalus microplus and Rhipicephalus sanguineus sensu lato) were identified. This study provides data on the ectoparasite fauna infesting domestic animals from Northeastern Brazil. The diagnosis and treatment of these parasites should not be underestimated, considering the role that hematophagous arthropods display as vectors of pathogens of medical and veterinary concern.(AU)

O número de animais domésticos infestados por ectoparasitos vivendo em estreito contato com seres humanos está aumentando, elevando o risco de infecção pelos patógenos transmitidos por vetores. Objetivou-se neste estudo avaliar a ocorrência de ectoparasitos infestando animais do nordeste do Brasil e discutir as implicações desse parasitismo na epidemiologia e no controle de doenças de importância médico-veterinária. De janeiro de 2017 a abril de 2019, artrópodes foram coletados de gatos, cães e cavalos, e identificados morfologicamente. Ectoparasitos foram removidos de 86 animais infestados provenientes de áreas urbanas e rurais. Foram identificados 401 espécimes (344 carrapatos e 57 pulgas) coletados de diferentes hospedeiros (10 (2,49%), 96 (23,94%) e 295 (73,57%) de gatos, cães e cavalos, respectivamente. Duas espécies de pulgas (Ctenocephalides canis e Ctenocephalides felis) e cinco espécies de carrapatos (Amblyomma ovale, Amblyomma sculptum, Dermacentornitens, Rhipicephalus microplus e Rhipicephalus sanguineus sensu lato) foram identificadas. Este estudo fornece informações sobre a ectofauna de animais domésticos do nordeste do Brasil. Portanto, o diagnóstico e o tratamento desses parasitos não devem ser subestimados, considerando que os artrópodes aqui relatados podem veicular patógenos de importância médico-veterinária.(AU)

Tick-borne pathogens infecting dogs from a highland swamp area / [Infecção em cães por patógenos transmitidos por carrapatos em uma área de brejo de altitude]

Objetivou-se neste estudo relatar a frequência e a identidade de patógenos transmitidos por carrapatos em cães residentes de uma área caracterizada por brejo de alta altitude. Amostras sanguíneas (n=203) foram coletadas e molecularmente analisadas via PCR (Babesia spp., Hepatozoon spp., Anaplasma spp. e Ehrlichia spp.) e sequenciamento de DNA. De todas as amostras analisadas, 8,87% (18/203) foram positivas a algum patógeno transmitido por carrapato. Especificamente, 5,42% (11/203) e 3,45% (7/203) foram positivos a Anaplasma platys e Ehrlichia canis, respectivamente. Este estudo fornece, pela primeira vez, evidência científica de infecção de cães por esses patógenos nessa área de alta altitude e reforça o provável papel de R. sanguineus s.l. como vetor de A. platys, principalmente considerando.se que muitos animais positivos eram infestados por essa espécie de carrapato.(AU)

Development and Reproduction of Chrysoperla externa (Hagen) (Neuroptera: Chrysopidae) Fed on Myzus persicae (Sulzer) (Hemiptera: Aphididae) Vectoring Potato leafroll virus (PLRV).

The aim of this study was to evaluate the biological parameters of Chrysoperla externa (Hagen) while feeding on Myzus persicae (Sulzer) acting as a vector of potato leafroll virus (PLRV). In laboratory experiments, three different diets were offered ad libitum to C. externa during the larval period: M. persicae fed on PLRV-infected potato leaves, M. persicae fed on uninfected potato leaves, and eggs of the factitious prey Anagasta kuehniella (Zeller) as the control. The following parameters were studied: the developmental time and survival rate of the larval and pupal stages, the sex ratio, the proportion of fertile females, female fecundity and egg viability, and the survival curve of the first 30 days after adult emergence. PLRV-infected aphids influenced the C. externa larval developmental time and survival compared to PLRV-uninfected aphids and A. kuehniella eggs. The pupal developmental time of C. externa was shorter when fed on aphids compared to A. kuehniella eggs, but no differences were recorded between the PLRV-infected and uninfected aphid diets. Additionally, no differences were observed for pupal survival and reproduction. However, adult survival was affected by the prey type, as 75% of C. externa control adults remained alive at an age of 30 days compared to 51 and 54% for those fed on PLRV-uninfected and infected aphids, respectively.

Complete thyroxine-binding globulin (TBG) deficiency produced by a mutation in acceptor splice site causing frameshift and early termination of translation (TBG-Kankakee).

Fourteen T4-binding globulin (TBG) variants have been identified at the gene level. They are all located in the coding region of the gene and 6 produce complete deficiency of TBG (TBG-CD). We now describe the first mutation in a noncoding region producing TBG-CD. The proband was treated for over 20 yr with L-T4 because of fatigue associated with a low concentration of serum total T4. Fifteen family members were studied showing low total T4 inherited as an X chromosome-linked trait, and affected males had undetectable TBG in serum. Sequencing of the entire coding region and promoter of the TBG gene revealed no abnormality. However, an A to G transition was found in the acceptor splice junction of intron II that produced a new HaeIII restriction site cosegregating with the TBG-CD phenotype. Sequencing exon 1 to exon 3 of TBG complementary DNA reverse transcribed from messenger RNA of skin fibroblasts from an affected male, confirmed a shift in the ag acceptor splice site. This results in the insertion of a G in exon 2 and causes a frameshift and a premature stop at codon 195. This early termination of translation predicts a truncated TBG lacking 201 amino acids.

Search for abnormalities of nuclear corepressors, coactivators, and a coregulator in families with resistance to thyroid hormone without mutations in thyroid hormone receptor beta or alpha genes.

The syndrome of resistance to thyroid hormone (RTH) is characterized by decreased tissue responsiveness to thyroid hormones. Inheritance is usually autosomal dominant due to mutations in the ligand-binding domain or adjacent hinge region of the thyroid hormone receptor beta (TRbeta) gene. Six of 65 families with the RTH phenotype studied in our laboratory had normal TRbeta1 and TRbeta2 gene sequences. Their clinical characteristics were not different from those of subjects with TRbeta gene mutations. Four of the 6 families were amenable to linkage analysis, and TRalpha involvement was excluded. Candidate genes were then evaluated for their possible involvement in the RTH phenotype in these 4 families: 2 coactivators [NCoA-1 (SRC-1) and NCoA-3 (AIB-1)], 2 corepressors (NCoR and SMRT), and a coregulator (RXRgamma). DNA was obtained from 8 affected subjects and 41 of 45 living first degree relatives. In 2 of the 4 families, the mode of inheritance could be determined by pedigree analysis and was found to be autosomal dominant. Linkage analyses were performed using polymorphic markers near or within the 5 candidate genes. When analyses were not informative or linkage could not be excluded, direct sequencing of the genes in question was performed. Involvement of NCoA-1 was excluded in all four families assuming autosomal dominant inheritance. Roles for NCoR, SMRT, and NCoA-3 were excluded in three and a role for RXRgamma was excluded in two of the four families. However, if the two families without proven dominant mode of inheritance were compound heterozygous, only the involvement of NCoA-1 could be excluded in both. Roles for NCoR, SMRT, and RXRgamma were excluded in one of these two families. Thus, NCoA-1 and RXRgamma genes were not found to be the cause of RTH in subjects without TR gene mutations even though the absence of NCoA-1 and RXRgamma is the cause of RTH in mice. Involvement of other candidate genes in the mediation of thyroid hormone action as well as intracellular hormone transport needs to be explored in these families with non-TRbeta, TRalpha RTH.

Cystic schwannomas of the jugular foramen: clinical and surgical remarks.

OBJECTIVE: The goals of this report were to outline the clinical presentation, radiological characteristics, surgical techniques, postoperative morbidity, and long-term follow-up results for cystic jugular foramen (JF) schwannomas and to describe their differences, compared with solid schwannomas involving the JF. METHODS: A retrospective analysis of radiological studies and surgical records identified five primarily cystic tumors among 21 cases of JF schwannomas that had been surgically treated at our institution. RESULTS: Two types of cystic JF schwannomas were observed, i.e., Type 1 lesions, which are single large cysts with thin ring-like enhancement of the tumor wall, and Type 2 lesions, which are multiple cysts with very irregular, thick enhancement of the cyst wall. The most common symptoms were hearing loss, ataxia, and headaches. Total surgical removal could be performed in all cases. The immediate postoperative findings indicated hearing improvement in three cases. No deterioration of lower cranial nerve function was observed. All patients were independent in the immediate postoperative period and in the long-term follow-up period (Karnofsky Performance Scale score, 90). CONCLUSION: Surgical treatment of cystic JF schwannomas can be very demanding because of generally stronger adhesion of the tumor capsule to the surrounding structures, fragile tumor capsules, and difficulty in identification of the arachnoidal planes in some cases. Early identification of the arachnoidal planes without opening of the cyst and sharp dissection may be useful. Careful intradural opening of the JF should be performed to achieve total removal of the last tumor portion within the JF. A comparison of these lesions with solid schwannomas involving the JF indicated that cystic tumors affected a younger population, with less preoperative swallowing impairment (P < 0.05). The immediate postoperative course in both types of cystic JF schwannomas was usually better than for solid lesions, because of minor postoperative cranial nerve morbidity, especially involving lower cranial nerve function, in the latter cases. Long-term follow-up data failed to demonstrate any significant differences in final patient outcomes, however.

Subarachnoid fat dissemination after resection of a cerebellopontine angle dysontogenic cyst: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: This case report illustrates the clinical and radiological relevance of extensive intracranial subarachnoid and ventricular dissemination in dysontogenic (dermoid) tumors. CLINICAL PRESENTATION: We describe a patient with a cerebellopontine angle dysontogenic tumor. Postoperatively, the cyst disseminated fat particles extensively into the subarachnoid space. Magnetic resonance imaging (MRI) studies revealed continuous dispersion of the fat particles into the cerebral cisterns, subarachnoid space, and ventricles. INTERVENTION: Eight years of clinical and MRI follow-up demonstrated neither neurological deterioration in the patient nor growth of the multiple lesions. CONCLUSION: Intracranial subarachnoid dissemination of fat material may occur during the preoperative or postoperative course of dermoid and epidermoid cysts. Aseptic meningitis or other complications such as hydrocephalus, seizures, or cranial nerve deficits also may occur owing to spillage of intracranial cyst contents into the subarachnoid space. MRI can detect the presence of fat drops that may adhere to the surrounding structures or migrate with the cerebrospinal fluid flow. Intracranial disseminated fat particles can remain silent without radiological or neurological change, justifying a wait-and-see approach. During long-term postoperative follow-up, however, regular MRI studies and clinical examinations are necessary to avoid potential complications.

Impact of computed tomographic and magnetic resonance imaging findings on surgical outcome in petroclival meningiomas.

OBJECTIVE: The preoperative radiological findings of computed tomographic and magnetic resonance imaging scans of 70 patients with petroclival meningioma were evaluated and statistically compared with the degree of surgical resection and patients' outcomes to depict the most important radiological findings that may influence surgical radicality and outcome. METHODS: The following parameters were evaluated: 1) tumor diameters; 2) tumor extension toward the middle fossa, the internal auditory canal, the brainstem, and the foramen magnum; 3) bone changes; 4) peritumoral edema; 5) signs of tumor infiltrative pattern; and 6) surgical radicality. Postoperative results were analyzed immediately after the surgery and in a long-term follow-up study. RESULTS: Larger tumors affected a younger population and presented a significantly shorter time until symptom onset. In the majority of cases (67%), the tumor extended to the parasellar region. Tumor extension toward the jugular foramen was found in 24% of the patients and reached the level of the foramen magnum in 18%. Irregular tumor margins were found in 67% of the tumors, and 50% of them presented peritumoral edema in addition. Interestingly, edema also was found in 20% of tumors with well-delineated margins. CONCLUSION: Tumor size, brainstem compression, and tumor extension laterally to the internal auditory canal did not influence either the degree of surgical resection or the long-term outcome (P > 0.05). Supratentorial tumor extension to the middle fossa and downward involving the caudal cranial nerves displayed a significant importance in regard to the surgical radicality and the patient's outcome, respectively (P < 0.05). Radiological evidence of infiltrative tumor pattern and peritumoral edema at the brainstem surface were important parameters regarding surgical radicality (P < 0.05). However, only peritumoral edema influenced the long-term results significantly.