Diffuse bipolar cells provide input to OFF parasol ganglion cells in the macaque retina

Parasol retinal ganglion cells are more sensitive to luminance contrast and respond more transiently at all levels of adaptation than midget ganglion cells. This may be due, in part, to differences between bipolar cells that provide their input, and the goal of these experiments was to study these differences. Midget bipolar cells are known to be presynaptic to midget ganglion cells. To identify the bipolar cells presynaptic to parasol cells, these ganglion cells were intracellularly injected with Neurobiotin, cone bipolar cells were immunolabeled, and the double-labeled material was analyzed. In the electron microscope, we found that DB3 diffuse bipolar cells labeled by using antiserum to calbindin D-28k were presynaptic to OFF parasol cells. In the confocal microscope, DB3 bipolars costratified with OFF parasol cell dendrites and made significantly more appositions with them than expected due to chance. Flat midget bipolar cells were labeled with antiserum to recoverin. Although they made a few appositions with parasol cells, the number was no greater than would be expected when two sets of processes have overlapping distributions in the inner plexiform layer. DB2 diffuse bipolar cells were labeled with antibodies to excitatory amino acid transporter 2, and they also made appositions with OFF parasol cells. These results suggest that DB2 bipolar cells are also presynaptic to OFF parasol ganglion cells, but midget bipolar cells are not. We estimate that midperipheral OFF parasol cells receive approximately 500 synapses from 50 DB3 bipolar cells that, in turn, receive input from 250 cones.     

Behaviour changes in dementia 1: Point of entry data of a prospective study

Objective. This article analyses behaviour changes in dementia at the point of entry to a longitudinal study. Design. Prospective, longitudinal study of behaviour in dementia, with autopsy follow-up. Setting. Subjects with dementia, living at home with a carer. All lived in Oxfordshire, UK. Participants. Ninety-seven people with dementia (Alzheimer's disease and/or vascular dementia) who were living at home with a carer. Measures. At 4-monthly intervals, the carers were interviewed and the subjects with dementia were assessed cognitively. Subjects' behaviour was assessed using the Present Behavioural Examination. This is an investigator-based, semi-structured interview consisting of eight main sections covering many different aspects of behaviour. The 121 main questions, with 66 further ‘nested’ questions, have been shown to have high reliability. Results. This article analyses the types of behaviour change reported by carers at the point of entry to this long-term study. Few correlations were found between behaviour and age, gender and time since onset of dementia. Some types of behaviour were significantly more prevalent in those with greater cognitive impairment. Conclusions. Many of these changes create problems for carers, for example increased aggressive behaviour, wandering, wakefulness at night, incontinence and persecutory ideas. In general, they are more prevalent in people with more severe dementia. © 1997 John Wiley & Sons, Ltd.     

Interactions between QnrB,QnrB Mutants,and DNA Gyrase

Plasmid-encoded protein QnrB1 protects DNA gyrase from ciprofloxacin inhibition. Using a bacterial two-hybrid system, we evaluated the physical interactions between wild-type and mutant QnrB1, the GyrA and GyrB gyrase subunits, and a GyrBA fusion protein. The interaction of QnrB1 with GyrB and GyrBA was approximately 10-fold higher than that with GyrA, suggesting that domains of GyrB are important for stabilizing QnrB1 interaction with the holoenzyme. Sub-MICs of ciprofloxacin or nalidixic acid reduced the interactions between QnrB1 and GyrA or GyrBA but produced no reduction in the interaction with GyrB or a quinolone-resistant GyrA:S83L (GyrA with S83L substitution) mutant, suggesting that quinolones and QnrB1 compete for binding to gyrase. Of QnrB1 mutants that reduced quinolone resistance, deletions in the C or N terminus of QnrB1 resulted in a marked decrease in interactions with GyrA but limited or no effect on interactions with GyrB and an intermediate effect on interactions with GyrBA. While deletion of loop B and both loops moderately reduced the interaction signal with GyrA, deletion of loop A resulted in only a small reduction in the interaction with GyrB. The loop A deletion also caused a substantial reduction in interaction with GyrBA, with little effect of loop B and dual-loop deletions. Single-amino-acid loop mutations had little effect on physical interactions except for a Δ105I mutant. Therefore, loops A and B may play key roles in the proper positioning of QnrB1 rather than as determinants of the physical interaction of QnrB1 with gyrase.     

Efficacy of Single and Combined Antibiotic Treatments of Anthrax in Rabbits

Respiratory anthrax is a fatal disease in the absence of early treatment with antibiotics. Rabbits are highly susceptible to infection with Bacillus anthracis spores by intranasal instillation, succumbing within 2 to 4 days postinfection. This study aims to test the efficiency of antibiotic therapy to treat systemic anthrax in this relevant animal model. Delaying the initiation of antibiotic administration to more than 24 h postinfection resulted in animals with systemic anthrax in various degrees of bacteremia and toxemia. As the onset of symptoms in humans was reported to start on days 1 to 7 postexposure, delaying the initiation of treatment by 24 to 48 h (time frame for mass distribution of antibiotics) may result in sick populations. We evaluated the efficacy of antibiotic administration as a function of bacteremia levels at the time of treatment initiation. Here we compare the efficacy of treatment with clarithromycin, amoxicillin-clavulanic acid (Augmentin), imipenem, vancomycin, rifampin, and linezolid to the previously reported efficacy of doxycycline and ciprofloxacin. We demonstrate that treatment with amoxicillin-clavulanic acid, imipenem, vancomycin, and linezolid were as effective as doxycycline and ciprofloxacin, curing rabbits exhibiting bacteremia levels of up to 10⁵ CFU/ml. Clarithromycin and rifampin were shown to be effective only as a postexposure prophylactic treatment but failed to treat the systemic (bacteremic) phase of anthrax. Furthermore, we evaluate the contribution of combined treatment of clindamycin and ciprofloxacin, which demonstrated improvement in efficacy compared to ciprofloxacin alone.     

Bone mineral content and density in Rett syndrome and their contributing factors

This study used densitometry to investigate the areal bone mineral density (aBMD) and bone mineral content (BMC) in an Australian Rett syndrome cohort and to assess how factors such as genotype, epilepsy, BMI, and mobility affect these parameters. The influence of lean tissue mass (LTM) and bone area (BA) on total body BMC (TBBMC) was also investigated. Participants, recruited from the Australian Rett Syndrome Database (ARSD), had TBBMC and lumbar spine (LS) and femoral neck (FN) aBMD measured using Dual energy x-ray absorptiometry. Mean height standardized Z scores and CIs for the bone outcomes were obtained from multiple regression models. The mean height Z score for the FN aBMD was low at -2.20, while the LS aBMD was -0.72. The TBBMC mean height Z score was -0.62, although once adjusted for BA and LTM, the mean was above zero, suggesting that low BMC can be explained by narrow bones and decreased muscle mass, likely secondary to decreased mobility. Multiple linear regression identified the p.R168× and p.T158M mutations as the strongest predictors of low aBMC and BMD for all bone outcomes. The strong relationship between genotype, BMC, and aBMD is likely underpinned by the strong relationship between LTM, mobility, and bone outcome measures.     

Admixture mapping identifies a locus on 6q25 associated with breast cancer risk in US Latinas

Among US Latinas and Mexican women, those with higher European ancestry have increased risk of breast cancer. We combined an admixture mapping and genome-wide association mapping approach to search for genomic regions that may explain this observation. Latina women with breast cancer (n= 1497) and Latina controls (n= 1272) were genotyped using Affymetrix and Illumina arrays. We inferred locus-specific genetic ancestry and compared the ancestry between cases and controls. We also performed single nucleotide polymorphism (SNP) association analyses in regions of interest. Correction for multiple-hypothesis testing was conducted using permutations (P(corrected)). We identified one region where genetic ancestry was significantly associated with breast cancer risk: 6q25 [odds ratio (OR) per Indigenous American chromosome 0.75, 95% confidence interval (CI): 0.65-0.85, P= 1.1 × 10(-5), P(corrected)= 0.02]. A second region on 11p15 showed a trend towards association (OR per Indigenous American chromosome 0.77, 95% CI: 0.68-0.87, P= 4.3 × 10(-5), P(corrected)= 0.08). In both regions, breast cancer risk decreased with higher Indigenous American ancestry in concordance with observations made on global ancestry. The peak of the 6q25 signal includes the estrogen receptor 1 (ESR1) gene and 5' region, a locus previously implicated in breast cancer. Genome-wide association analysis found that a multi-SNP model explained the admixture signal in both regions. Our results confirm that the association between genetic ancestry and breast cancer risk in US Latinas is partly due to genetic differences between populations of European and Indigenous Americans origin. Fine-mapping within the 6q25 and possibly the 11p15 loci will lead to the discovery of the biologically functional variant/s behind this association.     

I will always be with you: Traditional and complementary therapists’ perspectives on patient–therapist–doctor communication regarding treatment of Arab patients with cancer in Israel

Objective

In 2008, an Integrative Oncology Program was implemented at the Clalit Oncology Service in Haifa, Israel, to promote patients’ well-being during chemotherapy and advanced stages of disease. We hypothesized that studying the perceptions of Arab complementary and alternative medicine (CAM) therapists would facilitate development of a cross-culturally integrative oncology approach.

Methods

Semi-structured interviews were held with 27 Arab therapists who use medicinal herbs, the Quran and various CAM modalities, with the aim of characterizing their treatment practices and learning about their perspectives regarding conventional cancer care.

Results

Thematic analysis revealed that therapists act as go-betweens, mediating between patients and conventional physicians. Therapists translate diagnoses into Arabic and elucidate key concepts. They tend to perceive their role as gatekeepers accompanying patients through the conventional health system, referring them for further examinations, and providing CAM-based supportive care consultation.

Conclusions

CAM therapists have an essential role in supportive care of Arab patients with cancer. Triangular patient–therapist–oncologist communication may have an impact on patients’ experience and treatment quality.

Practice implications

Recognition of CAM therapists as mediators between patients’ health beliefs and conventional perceptions of care may improve doctor–patient dialogue and facilitate supportive care provision in a cross-cultural context.