PDZD7 is a modifier of retinal disease and a contributor to digenic Usher syndrome

Usher syndrome is a genetically heterogeneous recessive disease characterized by hearing loss and retinitis pigmentosa (RP). It frequently presents with unexplained, often intrafamilial, variability of the visual phenotype. Although 9 genes have been linked with Usher syndrome, many patients do not have mutations in any of these genes, suggesting that there are still unidentified genes involved in the syndrome. Here, we have determined that mutations in PDZ domain–containing 7 (PDZD7), which encodes a homolog of proteins mutated in Usher syndrome subtype 1C (USH1C) and USH2D, contribute to Usher syndrome. Mutations in PDZD7 were identified only in patients with mutations in other known Usher genes. In a set of sisters, each with a homozygous mutation in USH2A, a frame-shift mutation in PDZD7 was present in the sister with more severe RP and earlier disease onset. Further, heterozygous PDZD7 mutations were present in patients with truncating mutations in USH2A, G protein–coupled receptor 98 (GPR98; also known as USH2C), and an unidentified locus. We validated the human genotypes using zebrafish, and our findings were consistent with digenic inheritance of PDZD7 and GPR98, and with PDZD7 as a retinal disease modifier in patients with USH2A. Pdzd7 knockdown produced an Usher-like phenotype in zebrafish, exacerbated retinal cell death in combination with ush2a or gpr98, and reduced Gpr98 localization in the region of the photoreceptor connecting cilium. Our data challenge the view of Usher syndrome as a traditional Mendelian disorder and support the reclassification of Usher syndrome as an oligogenic disease.     

Anti-Helicobacter pylori activity of plants used in Mexican traditional medicine for gastrointestinal disorders

Aim of the study

Helicobacter pylori is the major etiological agent of chronic active gastritis and peptic ulcer disease and is linked to gastric carcinoma. Treatment to eradicate the bacteria failed in many cases, mainly due to antibiotic resistance, hence the necessity of developing better therapeutic regimens. Mexico has an enormous unexplored potential of medicinal plants. This work evaluates the in vitro anti-H. pylori activity of 53 plants used in Mexican traditional medicine for gastrointestinal disorders.

Materials and methods

To test the in vitro antibacterial activity, agar dilution and broth dilution methods were used for aqueous and methanolic extracts, respectively.

Results

Aqueous extracts of Artemisia ludoviciana subsp. mexicana, Cuphea aequipetala, Ludwigia repens,and Mentha × piperita (MIC 125 to <250 μg/ml) as well as methanolic extracts of Persea americana, Annona cherimola, Guaiacum coulteri, and Moussonia deppeana (MIC <7.5 to 15.6 μg/ml) showed the highest inhibitory effect.

Conclusions

The results contribute to understanding the mode of action of the studied medicinal plants and for detecting plants with high anti-Helicobacter pylori activity.     

Facilitating social support among community psychologists

Over the past few years, a network of regional coordinators has promoted a variety of community psychology activities in the United States and other countries, creating a base of social support for community psychologists in academic and field settings. This paper describes key organizing principles for creating viable support networks such as this one and presents specific examples of their use by the regional coordinators. The grassroots efforts of regional coordinators in stimulating social support, educational opportunities, resource exchanges, and a variety of other activities represent one of the more crucial and important functions undertaken by community psychologists and their organizations.     

Shortened erythrocyte sedimentation rate evaluation is applicable to hospitalised patients

BackgroundWestergren method, commonly used for erythrocyte sedimentation rate (ESR) determination, is simple and inexpensive. However, the 60 min required for the test are disadvantageous, especially for those departments/facilities where prompt evaluation is necessary. We investigated the possibility that earlier ESR recordings might correlate with standard 60-minute ESR and/or be predictive of the latter.MethodsDemographic and clinical data were collected from 220 randomly chosen adult patients hospitalised for various diseases in a medical department. ESR, determined by slightly modified Westergren method, was recorded at 15, 30 and 60 min. Correlation coefficients (r) between the standard and early ESR measurements were calculated for the entire group and for the separate subgroups divided according to patient age, sex and presence of anaemia or of inflammation.ResultsMean ± SD age of the patients was 61.3 ± 19.6, 55% were males; 45% had some inflammatory condition. Mean ± SD ESR values (mm) at 15, 30 and 60 min were 9.0 ± 12.1, 21.4 ± 21.8 and 35.9 ± 27.5, respectively. A statistically significant correlation was found between ESR measurements at 15 and 60 min (r = 0.833, p < 0.001). However, the strongest correlation was observed between 30 and 60 min measurements (r = 0.926, p < 0.001), irrespective of age, sex and presence of anaemia or of inflammation. Based on the ESR determination at 30 min (X), the predicted ESR value at 60 min (Y) could be calculated by a simple equation: Y = 10.7 + 1.2X.ConclusionSixty-minute ESR values can be predicted by the 30-minute estimation. Shortening the test by half an hour might bear practical importance.     

TGF-beta and mesenchymal hepatic involvement after visceral leishmaniasis

The liver involvement in the human visceral leishmaniasis (VL) has been related to parasitism and activated Kupffer cells with further occasional fibrotic alterations, especially after long-term disease without treatment. However, fibrotic alterations have been reported after therapy, whose clinical finding is the persistence of hepatomegaly. Fibrotic involvement of the liver after therapy was never well understood, and the aim of this study was to evaluate this finding through ultrastructural and morphometric analysis. A case–control study was performed with 20 patients (15 cases and five controls). Cases included patients with persistent hepatomegaly (residual) after treatment of VL submitted to liver biopsy to exclude other causes of liver enlargement, including serum tests of viral hepatitis. The material was evaluated by electron microcopy allowing ultrastructural with morphometric analysis of medium portion of hepatic lobule. Narrow sinusoidal lumen and prominent Kupffer cells were found with insignificant alterations of hepatocytes, pit, and endothelial cells. On ultrastructural analysis, the enlargement of the space of Disse was due to fibrous collagen, increase of number of Ito cells, and nonfibrous extracellular matrix that were associated with Kupffer cells enlargement. Immunohistochemistry showed an intense expression of TGF-beta in patients with VL. These findings suggest a production of TGF-beta by Kupffer cells that resulted in the characteristic fibrotic involvement of the liver. Residual hepatomegaly in visceral leishmaniasis could result from sustained Kupffer cell activation with perihepatocytic fibrosis. The authors are not part of any associations or commercial relationships that might represent conflicts of interest in the writing of this study (e.g., pharmaceutical stock ownership, consultancy, advisory board membership, relevant patents, or research funding). This article has financial support by the FAPESP (Grants 96/5875-8)     

Behavior and psychological functioning of young children of HIV-positive mothers in South Africa

Adults with HIV are living longer due to earlier diagnosis and increased access to antiretroviral medications. Therefore, fewer young children are being orphaned and instead, are being cared for by parents who know they are HIV positive, although they may be asymptomatic. Presently, it is unclear whether the psychological functioning of these young children is likely to be affected or, alternatively, whether it is only when a mother is ill, that children suffer adverse effects. We, thus, aimed to compare the behavior and psychological functioning of young children (aged 6–10 years) of HIV-positive and HIV-negative mothers. We also aimed to examine the association between HIV status disclosure and child outcomes. This study uses cross-sectional data from the baseline assessment of a randomized controlled trial conducted in Tshwane, South Africa. Participants (n=509) and their children were recruited from area health clinics. Among the 395 mothers with HIV, 42% reported symptoms of HIV disease. Multivariate linear regression models suggested that after adjusting for socio-demographic characteristics, children of HIV-positive mothers had significantly greater externalizing behaviors than children of HIV-negative mothers. Importantly, children whose mothers were symptomatic had greater internalizing and externalizing behaviors compared with children of HIV-negative mothers, but this was not true for children of asymptomatic mothers. Additionally, among children of HIV-positive mothers, those who had been told their mothers were sick compared with children who had been told nothing had less internalizing and externalizing behaviors and improved daily living skills. This study, therefore, provides evidence that maternal HIV disease can affect the behaviors of young children in South Africa but, importantly, only when the mothers are symptomatic from their disease. Furthermore, results suggest that disclosure of maternal illness but not HIV status was associated with improved behavior and psychological functioning among young children.     

From biomedical teaching to biopsychosocial education: a process of change in a Finnish medical school

A group of clinicians, teachers and researchers in the University of Oulu have been worried for years about the predominantly biomedical orientation in the local Faculty of Medicine. Therefore, a project group was founded in 1992 to develop the medical degree programme towards a more comprehensive model. This article introduces the main strategies used in the process of change and describes the challenges encountered during the process. There are still many problems in the education of medical students towards a patient and family orientation and in the effort to change the whole medical culture of the university from a biomedical to a biopsychosocial approach. However, in the postgraduate education of general practitioners, we no longer prefer to teach only doctors, but education on the biopsychosocial model will also be arranged to the interdisciplinary teams working in the municipalities in the Province of Oulu in Finland.     

Low-frequency axial ultrasound velocity correlates with bone mineral density and cortical thickness in the radius and tibia in pre- and postmenopausal women

Summary  

Axial transmission velocity of a low-frequency first arriving signal (V _LF) was assessed in the radius and tibia of 254 females, and compared to site-matched pQCT measurements. V _LF best correlated with cortical BMD, but significantly also with subcortical BMD and cortical thickness. Correlations were strongest for the radius in postmenopausal females.     

Changes in β-giardin sequence of <Emphasis Type="Italic">Giardia intestinalis</Emphasis> sensitive and resistant to albendazole strains

Giardia intestinalis can develop resistance to albendazole, although the molecular mechanism is not understood. The aim of this study was to investigate the differences and permanent mutation in the β-giardin gene of G. intestinalis strains: sensitive, resistant, or recovered-resistance to albendazole. The β-giardin gene was amplified by nested polymerase chain reaction. The IC₅₀ values varied from 0.29 to 0.38 μg/mL for strains sensitive to albendazole. For resistant strains, the IC₅₀ range was 1.31–2.12 μg/mL. Recovered-sensitivity albendazole strains’ IC₅₀ values were 0.33–0.49 μg/mL, and for strains with recovered-resistance, the IC₅₀ was 1.42–2.74 μg/mL. β-giardin amplicon (720 bp) was sequenced and analysis sequence revealed several amino acid mutations from resistant and recovered-sensitive strains of G. intestinalis. Most of the mutations were located in the ROD domain of β-giardin with a change from the sequence “TIARERA” in sensitive strains instead “IDRPRE” in resistant strains. A comparative sequence analysis in resistant, recovered-sensitive, and resistant-recovered strains revealed permanent mutation. This is the first report of combinatorial serine–proline–arginine repeats in the ROD domain of β-giardin, whereas such repeats have been reported previously in the HEAD domain of SF-assemblin proteins. This is the first time that the resistance to albendazole correlates with genetics but it is not necessarily caused by mutations in the β-giardin gene of G. intestinalis.