Variants in the toll-like receptor signaling pathway and clinical outcomes of malaria

Background. Malaria is one of the most significant infectious diseases in the world and is responsible for a large proportion of infant deaths. Toll-like receptors (TLRs), key components of innate immunity, are central to countering infection. Variants in the TLR-signaling pathway are associated with susceptibility to infectious diseases. Methods. We genotyped single nucleotide polymorphisms ( SNPs) of the genes associated with the TLR-signaling pathway in patients with mild malaria and individuals with asymptomatic Plasmodium infections by means of polymerase chain reaction. Results. Genotype distributions for the TLR-1 I602S differed significantly between patients with mild malaria and persons with asymptomatic infection. The TLR-1 602S allele was associated with an odds ratio ( OR) of 2.2 ( P = .003; P(corrected) = .015) for malaria among patients with mild malaria due to any Plasmodium species and 2.1 ( P = .015; P(corrected) = .75) among patients with mild malaria due to Plasmodium falciparum only. The TLR-6 S249P SNP showed an excess of homozygotes for the TLR-6 249P allele in asymptomatic persons, compared with patients with mild malaria due to any Plasmodium species (OR 2.1; 95% confidence interval [CI], 1.1-4.2; P = .01; P(corrected) = .05), suggesting that the TLR-6 249S allele may be a risk factor for malaria ( OR, 2.0; 95% CI, 1.1-3.7; P = 0.01; P(corrected) = .05). The TLR-9-1486C allele showed a strong association with high parasitemia ( P < .001). Conclusions. Our findings indicate that the TLR-1 and TLR- 6 variants are significantly associated with mild malaria, whereas the TLR-9-1486C/T variants are associated with high parasitemia. These discoveries may bring additional understanding to the pathogenesis of malaria.

Purines, creatine, defective methylation and their biochemical and clinical relationship

Marinus Duran; Isabel G. Tavares de Almeida; Helena P. Gaspar Tomás

Asthma Polymorphic Loci genotyping in Madeira population: identification of potential genetic markers of disease susceptibility, severity and clinical relevance

Asthma is a complex disease, influenced by both environmental and genetic factors. In this study, the analysis of multiple environmental factos assessed by questionnaire and the genotyping of SNPs IL131c.144 G/A, IL41590 C/T, IL41RP2 253183, ADRB21c.16 A/G, ADAM331V4 C/G, ADAM331S1 c.710 G/A, GSDML1236 C/T and STAT6121 C/T were performed in a sample of Madeiran asthmatic patients and their families, and their association to asthma susceptibility and severity was assessed. Family, environmental, social and individual factos such as the presence of rhinitis in one of the parents,the habitation conditions, the family smoking habits, individual food habits and allergen sensitivity, were found to account for asthma severity. IL41590*T and IL41RP2*183$ alleles as well as the combined genotypes IL41590*CT/IL41590*TT and IL41 RP2*253183/IL41RP2*253183 were associated to both asthma susceptibility and severity.GSDML1236*TT was found associated only to asthma severity.Allele ADAM331 V4*C was significantly overM transmitted to asthmatic offspring being linked with the disease by TDT. These findings suggest that in addition to environmental influences, IL41 590 C/T, IL41RP2 253183, ADAM331V4 C/G and GSDML1236 C/T SNPs may constitute important genetic factos contributing to asthmasusceptibility and/or severity in Madeira population.

Neurobiology and clinical implications of lucid dreaming

Several lines of evidence converge to the idea that rapid eye movement sleep (REMS) is a good model to foster our understanding of psychosis. Both REMS and psychosis course with internally generated perceptions and lack of rational judgment, which is attributed to a hyperlimbic activity along with hypofrontality. Interestingly, some individuals can become aware of dreaming during REMS, a particular experience known as lucid dreaming (LD), whose neurobiological basis is still controversial. Since the frontal lobe plays a role in self-consciousness, working memory and attention, here we hypothesize that LD is associated with increased frontal activity during REMS. A possible way to test this hypothesis is to check whether transcranial magnetic or electric stimulation of the frontal region during REMS triggers LD. We further suggest that psychosis and LD are opposite phenomena: LD as a physiological awakening while dreaming due to frontal activity, and psychosis as a pathological intrusion of dream features during wake state due to hypofrontality. We further suggest that LD research may have three main clinical implications. First, LD could be important to the study of consciousness, including its pathologies and other altered states. Second, LD could be used as a therapy for recurrent nightmares, a common symptom of depression and post-traumatic stress disorder. Finally, LD may allow for motor imagery during dreaming with possible improvement of physical rehabilitation. In all, we believe that LD research may clarify multiple aspects of brain functioning in its physiological, altered and pathological states.

Growth and mineral nutrition of Solanum americanum

Um experimento em casa de vegetação foi conduzido entre novembro de 1995 e abril de 1996 na FCAV/UNESP, Brasil, objetivando estudar a produção de matéria seca, a distribuição e o acúmulo de macronutrientes por Solanum americanum - uma importante planta infestante de culturas anuais e perenes no Brasil. As plantas foram cultivadas em vasos de 7 L com substrato de areia, os quais foram irrigados diariamente com solução nutritiva de Hoagland & Arnon. O delineamento experimental foi inteiramente casualizado, com quatro repetições. Os tratamentos corresponderam às épocas de avaliação, em intervalos de 14 dias, iniciando-se 21 dias após a emergência (DAE). em cada avaliação, as plantas de quatro vasos foram analisadas quanto à produção de matéria seca e ao conteúdo de macronutrientes. S. americanum apresentou pequeno acúmulo de matéria seca e de macronutrientes no início da fase experimental. Esses acúmulos intensificaram-se após 77 DAE, atingindo o máximo valor teórico aos 142, 142, 164, 149, 140, 149 e 152 DAE, para matéria seca, N, P, K, Ca, Mg e S, respectivamente. K e N foram os macronutrientes acumulados em maior quantidade por plantas de S. americanum.

Growth and mineral nutrition of Ipomoea quamoclit

Um experimento em casa de vegetação foi conduzido entre novembro de 2006 e abril de 2007, na FCAV/UNESP, Brasil, objetivando estudar a produção de massa seca, a distribuição e o acúmulo de macronutrientes por Ipomoea quamoclit, uma importante planta infestante de culturas anuais e perenes no Brasil. As plantas foram cultivadas em vasos de 7 L com substrato de areia, que foram irrigados diariamente com solução nutritiva de Hoagland & Arnon. O delineamento experimental foi inteiramente casualizado, com quatro repetições. Os tratamentos corresponderam às épocas de avaliação, em intervalos de 14 dias, iniciando-se 21 dias após a emergência (DAE). em cada avaliação, as plantas de quatro vasos foram analisadas quanto à produção de massa seca e ao conteúdo de macronutrientes. I. quamoclit apresentou pequeno acúmulo de massa seca e de macronutrientes no início da fase experimental. Esses acúmulos intensificaram-se após 77 DAE, atingindo o máximo valor teórico aos 146, 143, 140, 149, 142, 153 e 124 DAE, para massa seca, N, P, K, Ca, Mg e S, respectivamente. K e N foram os macronutrientes acumulados em maior quantidade por plantas de I. quamoclit.

Biochemical, histopathological and clinical evaluation of delayed effects caused by methamidophos isoforms and TOCP in hens: Ameliorative effects using control of calcium homeostasis

This work evaluated the potential of the isoforms of methamidophos to cause organophosphorus-induced delayed neuropathy (OPIDN) in hens. In addition to inhibition of neuropathy target esterase (NTE) and acetylcholinesterase (AChE), calpain activation, spinal cord lesions and clinical signs were assessed. The isoforms (+)-, (+/-)- and (-)-methamidophos were administered at 50 mg/kg orally; tri-ortho-cresyl phosphate (TOCP) was administered (500 mg/kg, po) as positive control for delayed neuropathy. The TOCP hens showed greater than 80% and approximately 20% inhibition of NTE and AChE in hen brain, respectively. Among the isoforms of methamidophos, only the (+)-methamidophos was capable of inhibiting NTE activity (approximately 60%) with statistically significant difference compared to the control group. Calpain activity in brain increased by 40% in TOCP hens compared to the control group when measured 24h after dosing and remained high (18% over control) 21 days after dosing. Hens that received (+)-methamidophos had calpain activity 12% greater than controls. The histopathological findings and clinical signs corroborated the biochemical results that indicated the potential of the (+)-methamidophos to be the isoform responsible for OPIDN induction. Protection against OPIDN was examined using a treatment of 2 doses of nimodipine (1 mg/kg, i.m.) and one dose of calcium gluconate (5 mg/kg, iv.). The treatment decreased the effect of OPIDN-inducing TOCP and (+)-methamidophos on calpain activity, spinal cord lesions and clinical signs. (C) 2012 Elsevier B.V. All rights reserved.

Sociodemographic and clinical characteristics, causal factors and evolution of a group of patients with chronic urticaria-angioedema

CONTEXTO E OBJETIVO: Urticária-angioedema crônico é enfermidade freqüente, complexa e multicausal. O objetivo foi estudar as características sociodemográficas, clínicas, os fatores causais, agravantes e a evolução da enfermidade. TIPO DE ESTUDO E LOCAL: Descritivo e prospectivo, realizado no ambulatório de Dermatologia da Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (Unesp). MÉTODOS: Foram avaliados pacientes com diagnóstico de urticária-angioedema crônico através de dados sociodemográficos, anamnese, exames dermatológico, clínico e laboratorial, com ênfase nos fatores causais, agravantes e na evolução da enfermidade. RESULTADOS: 125 pacientes foram incluídos, 95 mulheres e 30 homens. Predominaram mulheres de 30 a 40 anos e homens de 10 a 20 anos. A idade média foi de 35 anos para as mulheres e 32 anos para os homens. Predominaram pacientes de raça branca, residentes em zona urbana e casados. O tempo médio de doença foi de 45,6 meses e de cada lesão foi de 5,6 horas. A metade dos casos tinha surtos diariamente e associação de urticária com angioedema. Não houve horário preferencial de aparecimento dos surtos, mas o noturno foi o horário de piora mais citado. A causa foi esclarecida em 37,6%, predominando as infecções. O estresse foi o agravante mais referido. O tempo médio de acompanhamento foi de 11,7 meses e 60% evoluíram para o controle, 32% melhoraram, 9% mantiveram-se inalterados e um caso piorou. CONCLUSÕES: Urticária-angioedema ocorreu mais em mulheres de meia-idade. A causa foi esclarecida em um terço dos pacientes e metade deles teve controle da doença em aproximadamente um ano.

Vaginal Flora Alterations and Clinical Symptoms in Low-Risk Pregnant Women

Background: To evaluate associations between alterations in vaginal flora and clinical symptoms in low-risk pregnant women. Methods: Vaginal specimens from 245 pregnant women were analyzed by microscopy for vaginal flora. Signs and symptoms of vaginal infection were determined by patient interviews and gynecologic examinations. Results: Abnormal vaginal flora was identified in 45.7% of the subjects. The final clinical diagnoses were bacterial vaginosis (21.6%), vaginal candidosis (10.2%), intermediate vaginal flora (5.2%), aerobic vaginitis (2.9%), mixed flora (2.9%) and other abnormal findings (2.9%). The percentage of women with or without clinical signs or symptoms was not significantly different between these categories. The presence of vaginal odor or vaginal discharge characteristics was not diagnostic of any specific flora alteration; pruritus was highly associated with candidosis (p < 0.0001). Compared to women with normal flora, pruritus was more prevalent in women with candidosis (p < 0.0001), while vaginal odor was associated with bacterial vaginosis (p = 0.0026). Conclusion: The prevalence of atypical vaginal flora is common in our low-risk pregnant population and is not always associated with pathology. The occurrence of specific signs or symptoms does not always discriminate between women with different types of atypical vaginal flora or between those with abnormal and normal vaginal flora. Copyright (C) 2010 S. Karger AG, Basel

Body dysmorphic disorder among dermatologic patients: Prevalence and clinical features

Background: An impairing preoccupation with a nonexistent or slight defect in appearance is the core symptom of body dysmorphic disorder (ODD), a psychiatric condition common in dermatology settings.Objective: We sought to determine the prevalence of ODD in dermatologic patients, comparing general and cosmetic settings, and describing some demographic and clinical characteristics.Methods: In all, 300 patients were consecutively assessed. Screening and diagnoses were performed with validated instruments plus a best estimate diagnosis procedure. The final sample comprised 150 patients in the cosmetic group, 150 patients in the general dermatology group, and 50 control subjects. Standard statistical analyses were performed (chi(2), nonparametric tests, logistic regression).Results: The current prevalence was higher in the cosmetic group (14.0%) compared with general (6.7%) and control (2.0%) groups. No patient had a previous diagnosis. Frequently the reason for seeking dermatologic treatment was not the main ODD preoccupation. Patients with ODD from the cosmetic group were in general unsatisfied with the results of dermatologic treatments.Limitations: Cross-sectional study conducted in a university hospital is a limitation. It is uncertain if the findings can be generalized. Retrospective data regarding previous treatments are not free from bias.Conclusions: BUD is relatively common in a dermatologic setting, especially among patients seeking cosmetic treatments. These patients have some different features compared with general dermatology patients. Dermatologists should be aware of the clinical characteristics of ODD to identify and refer these patients to mental health professionals. (J Am Acad Dermatol 2010;63:235-43.)

BODY DYSMORPHIC DISORDER IN PATIENTS WITH OBSESSIVE-COMPULSIVE DISORDER: PREVALENCE and CLINICAL CORRELATES

Background The prevalence, sociodemographic aspects, and clinical features of body dysmorphic disorder (BDD) in patients with obsessivecompulsive disorder (OCD) have been previously addressed in primarily relatively small samples. Methods We performed a cross-sectional demographic and clinical assessment of 901 OCD patients participating in the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders. We used the Structured Clinical Interview for DSM-IV Axis I Disorders; Yale-Brown Obsessive-Compulsive Scale; Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS); Brown Assessment of Beliefs Scale; Clinical Global Impression Scale; and Beck Depression and Anxiety Inventories. Results The lifetime prevalence of BDD was 12.1%. The individuals with comorbid BDD (OCD-BDD; n = 109) were younger than were those without it. In addition, the proportions of single and unemployed patients were greater in the OCD-BDD group. This group of patients also showed higher rates of suicidal behaviors; mood, anxiety, and eating disorders; hypochondriasis; skin picking; Tourette syndrome; and symptoms of the sexual/religious, aggressive, and miscellaneous dimensions. Furthermore, OCD-BDD patients had an earlier onset of OC symptoms; greater severity of OCD, depression, and anxiety symptoms; and poorer insight. After logistic regression, the following features were associated with OCD-BDD: current age; age at OCD onset; severity of the miscellaneous DY-BOCS dimension; severity of depressive symptoms; and comorbid social phobia, dysthymia, anorexia nervosa, bulimia nervosa, and skin picking. Conclusions Because OCD patients might not inform clinicians about concerns regarding their appearance, it is essential to investigate symptoms of BDD, especially in young patients with early onset and comorbid social anxiety, chronic depression, skin picking, or eating disorders. Depression and Anxiety 29: 966-975, 2012. (C) 2012 Wiley Periodicals, Inc.

EULAR/PRINTO/PRES criteria for Henoch-Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part I: Overall methodology and clinical characterisation

Objectives To report methodology and overall clinical, laboratory and radiographic characteristics for Henoch-Schonlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) classification criteria.Methods The preliminary Vienna 2005 consensus conference, which proposed preliminary criteria for paediatric vasculitides, was followed by a EULAR/PRINTO/PRES-supported validation project divided into three main steps. Step 1: retrospective/prospective web-data collection for HSP, c-PAN, c-WG and c-TA, with age at diagnosis <= 18 years. Step 2: blinded classification by consensus panel of a subgroup of 280 cases (128 difficult cases, 152 randomly selected) enabling expert diagnostic verification. Step 3: Ankara 2008 Consensus Conference and statistical evaluation (sensitivity, specificity, area under the curve, kappa-agreement) using as 'gold standard' the final consensus classification or original treating physician diagnosis.Results A total of 1183/1398 (85%) samples collected were available for analysis: 827 HSP, 150 c-PAN, 60 c-WG, 87 c-TA and 59 c-other. Prevalence, signs/symptoms, laboratory, biopsy and imaging reports were consistent with the clinical picture of the four c-vasculitides. A representative subgroup of 280 patients was blinded to the treating physician diagnosis and classified by a consensus panel, with kappa-agreement of 0.96 for HSP (95% CI 0.84 to 1), 0.88 for c-WG (95% CI 0.76 to 0.99), 0.84 for c-TA (95% CI 0.73 to 0.96) and 0.73 for c-PAN (95% CI 0.62 to 0.84), with an overall. of 0.79 (95% CI 0.73 to 0.84).Conclusion EULAR/PRINTO/PRES propose validated classification criteria for HSP, c-PAN, c-WG and c-TA, with substantial/almost perfect agreement with the final consensus classification or original treating physician diagnosis.

Molar incisor hypomineralization: prevalence, severity and clinical consequences in Brazilian children

Background.The prevalence of molar incisor hypomineralization (MIH) varies considerably around the world; however, few studies have examined MIH in South American countries.Objective.To evaluate the prevalence, severity, and clinical consequences of MIH in Brazilian children residing in rural and urban areas of the municipality of Botelhos, Minas Gerais, Brazil.Methods.Children aged 6 to 12 years (n = 918) with all four-first permanent molars erupted had these teeth evaluated according to the European Academy of Paediatric Dentistry (EAPD) criteria. The examinations were conducted by two previously trained examiners, and the dental impact caused by MIH was evaluated with the Decayed, Missing and Filled Teeth (DMFT) index (WHO).Results.Molar incisor hypomineralization was present in 19.8% of the 918 children, with a higher prevalence in rural areas. The majority of the defects presented were demarcated opacities without post-eruptive structural loss, which has been considered as mild defects. Children with MIH had higher DMFT values.Conclusion.Despite the high prevalence of MIH, the severity of the defects was mild. The results indicate a positive association between MIH and the presence of dental caries.