Evaluating Retinal Function in Age-Related Maculopathy with the ERG Photostress Test

PURPOSE. To evaluate the diagnostic potential of the electroretinogram (ERG) photostress test and the focal cone ERG in age-related maculopathy (ARM). METHODS. The cohort comprised 31 patients with ARM and 27 age-matched control subjects. The ERG photostress test was used to monitor cone adaptation after intense light adaptation. Focal 41- and 5-Hz cone ERGs were recorded monocularly (central 20°) to assess steady state retinal function. Univariate analysis identified electrophysiological parameters that differed between groups, and receiver operating characteristic (ROC) curves were constructed to assess their diagnostic potential. Logistic regression analysis determined the diagnostic potential of a model incorporating several independent predictors of ARM. RESULTS. The rate of recovery of the ERG photostress test was reduced (recovery was slower) in subjects with ARM. The parameter exhibited good diagnostic potential (P = 0.002, area under ROC curve = 0.74). The implicit times of the 5-Hz (a-wave, P = 0.002; b-wave, P < 0.001) and the 41-Hz (P < 0.001) focal cone ERGs were increased, and the 41-Hz focal cone ERG amplitude (P = 0.003) and focal to full-field amplitude ratio (P = 0.001) were reduced in the ARM group. Logistic regression analysis identified three independent predictors of ARM, including the rate of recovery of the ERG photostress test. CONCLUSIONS. Early ARM has a marked effect on the kinetics of cone adaptation. The clinical application of the ERG photostress test increases the sensitivity and specificity of a model for the diagnosis of ARM. Improved assessment of the functional integrity of the central retina will facilitate early diagnosis and evaluation of therapeutic interventions

A taxonomy for community-based care programs focused on HIV/AIDS prevention, treatment, and care in resource-poor settings

Community-based care (CBC) can increase access to key services for people affected by HIV/AIDS through the mobilization of community interests and resources and their integration with formal health structures. Yet, the lack of a systematic framework for analysis of CBC focused on HIV/AIDS impedes our ability to understand and study CBC programs. We sought to develop taxonomy of CBC programs focused on HIV/AIDS in resource-limited settings in an effort to understand their key characteristics, uncover any gaps in programming, and highlight the potential roles they play. Our review aimed to systematically identify key CBC programs focused on HIV/AIDS in resource-limited settings. We used both bibliographic database searches (Medline, CINAHL, and EMBASE) for peer-reviewed literature and internet-based searches for gray literature. Our search terms were &#x2018;HIV&#x2019; or &#x2018;AIDS&#x2019; and &#x2018;community-based care&#x2019; or &#x2018;CBC&#x2019;. Two co-authors developed a descriptive taxonomy through an iterative, inductive process using the retrieved program information. We identified 21 CBC programs useful for developing taxonomy. Extensive variation was observed within each of the nine categories identified: region, vision, characteristics of target populations, program scope, program operations, funding models, human resources, sustainability, and monitoring and evaluation strategies. While additional research may still be needed to identify the conditions that lead to overall program success, our findings can help to inform our understanding of the various aspects of CBC programs and inform potential logic models for CBC programming in the context of HIV/AIDS in resource-limited settings. Importantly, the findings of the present study can be used to develop sustainable HIV/AIDS-service delivery programs in regions with health resource shortages

Quantitative imaging of concentrated suspensions under flow

We review recent advances in imaging the flow of concentrated suspensions, focussing on the use of confocal microscopy to obtain time-resolved information on the single-particle level in these systems. After motivating the need for quantitative (confocal) imaging in suspension rheology, we briefly describe the particles, sample environments, microscopy tools and analysis algorithms needed to perform this kind of experiments. The second part of the review focusses on microscopic aspects of the flow of concentrated model hard-sphere-like suspensions, and the relation to non-linear rheological phenomena such as yielding, shear localization, wall slip and shear-induced ordering. Both Brownian and non-Brownian systems will be described. We show how quantitative imaging can improve our understanding of the connection between microscopic dynamics and bulk flow.Comment: Review on imaging hard-sphere suspensions, incl summary of methodology. Submitted for special volume 'High Solid Dispersions' ed. M. Cloitre, Vol. xx of 'Advances and Polymer Science' (Springer, Berlin, 2009); 22 pages, 16 fig

Expanding the diversity of mycobacteriophages: Insights into genome architecture and evolution

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists. © 2011 Hatfull et al

Short-term beneficial effects of methylene blue on kidney damage in septic shock patients

Contains fulltext : 71022.pdf (publisher's version ) (Closed access)OBJECTIVE: We previously demonstrated that upregulation of renal inducible nitric oxide synthase (iNOS) is associated with proximal tubule injury during systemic inflammation in humans. In this study we investigated the short-term effect of methylene blue (MB), an inhibitor of the NO pathway, on kidney damage and function in septic shock patients. DESIGN AND SETTING: A prospective clinical study conducted in an intensive care unit. PATIENTS: Nine patients (four men, five women, mean age 71 +/- 3 years) with confirmed or suspected bacterial infection and with refractory septic shock defined as a mean arterial pressure or = 0.2 microg/kg per minute. INTERVENTIONS: A 4 h continuous intravenous infusion of 1 mg/kg MB per hour. MEASUREMENTS AND RESULTS: The urinary excretion of NO metabolites decreased with median 90% (range 75-95%) from baseline to 6 h after MB administration. The first 24 h creatinine clearance improved by 51% (18-173%) after MB treatment but was still strongly impaired. During the first 6 h after the start of MB treatment both the urinary excretion of cytosolic glutathione S-transferase A1-1 and P1-1, markers for proximal and distal tubule damage, respectively, decreased by 45% (10-70%) and 70% (40-85) vs. baseline. After termination of the MB infusion the NO metabolites and markers of tubular injury returned to pretreatment levels. CONCLUSIONS: In septic patients with refractory shock short-term infusion of MB is associated with a decrease in NO production and an attenuation of the urinary excretion of renal tubular injury markers

Nitric oxide differentially regulates renal ATP-binding cassette transporters during endotoxemia

Nitric oxide (NO) is an important regulator of renal transport processes. In the present study, we investigated the role of NO, produced by inducible NO synthase (iNOS), in the regulation of renal ATP-binding cassette (ABC) transporters in vivo during endotoxemia. Wistar–Hannover rats were injected with lipopolysaccharide (LPS+) alone or in combination with the iNOS inhibitor, aminoguanidine. Controls received detoxified LPS (LPS−). After LPS+, proximal tubular damage and a reduction in renal function were observed. Furthermore, iNOS mRNA and protein, and the amount of NO metabolites in plasma and urine, increased compared to the LPS− group. Coadministration with aminoguanidine resulted in an attenuation of iNOS induction and reduction of renal damage. Gene expression of 20 ABC transporters was determined. After LPS+, a clear up-regulation in Abca1, Abcb1/P-glycoprotein (P-gp), Abcb11/bile salt export pump (Bsep), and Abcc2/multidrug resistance protein (Mrp2) was found, whereas Abcc8 was down-regulated. Up-regulation of Abcc2/Mrp2 was accompanied by enhanced calcein excretion. Aminoguanidine attenuated the effects on transporter expression. Our data indicate that NO, produced locally by renal iNOS, regulates the expression of ABC transporters in vivo. Furthermore, we showed, for the first time, expression and subcellular localization of Abcb11/Bsep in rat kidney

A randomized clinical trial comparing hydrocolloid, phenytoin and simple dressings for the treatment of pressure ulcers [ISRCTN33429693]

BACKGROUND: Pressure sores are important and common complications of spinal cord injury. Many preventive and therapeutic approaches have been tried and new trials are evolving. One relatively recent method is application of a hydrocolloid dressing (HD). In this study we compared the therapeutic effects of HD on pressure ulcer healing with two other topical applications, phenytoin cream (PC) and simple dressing (SD). METHODS: Ninety-one stage I and stage II pressure ulcers of 83 paraplegic male victims of the Iran-Iraq war were randomly allocated to three treatment groups. Mean age and weight of the participants were 36.64 ± 6.04 years and 61.12 ± 5.08 kg, respectively. All the patients were managed in long term care units or in their homes for 8 weeks by a team of general practitioners and nurses, and the ulcer status was recorded as "Complete healing", "Partial healing", "Without improvement" and "Worsening". RESULTS: Complete healing of ulcers, regardless of location and stage, was better in the HD group than the PC [23/31(74.19%) vs 12/30(40%); difference: 34.19%, 95% CI = 10.85–57.52, (P < 0.01)] or the SD [23/31(74.19%) vs 8/30(26.66%); difference: 47.53%, 95% CI = 25.45–69.61, (P < 0.005)] groups. Complete healing of stage I ulcers in the HD group [11/13(85%)] was better than in the SD [5/11(45%); difference: 40%, 95% CI = 4.7–75.22, (P < 0.05)] or PC [2/9 (22%); difference: 63%, 95% CI = 29.69–96.3, (P < 0.005)] groups. Complete healing of stage II ulcer in the HD group [12/18 (67%)] was better than in the SD group [3/19(16%); difference: 51%, 95% CI = 23.73–78.26, (P < 0.005)], but not significantly different from the PC group [10/21 (48%); difference: 19%, 95% CI = -11.47–49.47, (P > 0.05)]. We performed a second analysis considering only one ulcer per patient (i.e. 83 ulcers in 83 patients). This "per patient" analysis showed that complete ulcer healing in the HD group was better than in the PC [20/28(71.4%) vs 11/28 (39.3%); difference: 32.1%, 95% CI = 7.4–56.7, (P < 0.01)] or SD [20/28(71.4%) vs 8/27 (29.6%); difference: 41.8%, 95% CI = 17.7–65.8, (P < 0.005)] groups. CONCLUSION: We deduced that HD is the most effective method investigated for treating stage I and II pressure ulcers in young paraplegic men

Investigation of relationship between vitamin D status and reproductive fitness in Scottish hill sheep

There is a growing interest in the influence of vitamin D on ovine non-skeletal health. The aim of this study was to explore the relationship between pre-mating vitamin D status, as assessed by serum concentrations of 25-Hydroxyvitamin D [25(OH)D; comprising D2 and D3] and subsequent reproductive performance of genetically unimproved Scottish Blackface (UBF), genetically improved Scottish Blackface (IBF) and Lleyn ewes kept under Scottish hill conditions. 25-Hydroxyvitamin D2 (25(OH)D2) and 25-Hydroxyvitamin D3 (25(OH)D3) concentrations were determined in serum samples harvested in November from ewes grazed outdoors. There were no significant differences in 25(OH)D2concentrations amongst the 3 genotypes. Lleyn ewes had significantly higher 25(OH)D3 and 25(OH)D concentrations than both Scottish Blackface ewe genotypes, whereas these vitamin D parameters did not differ significantly between the UBF and IBF ewes. Concentrations of 25(OH)D3 and 25(OH)D were positively associated with subsequent birth weights of singleton and of twin lamb litters. No significant associations between vitamin D status and number of lambs born or weaned per ewe were found. This study demonstrates that concentrations of cutaneously-derived 25(OH)D3, but not of orally consumed 25(OH)D2, differed between breeds. The positive association between ewe vitamin D status and offspring birth weight highlights the need for further investigations

A practical guide to the simultaneous determination of protein structure and dynamics using metainference

Accurate protein structural ensembles can be determined with metainference, a Bayesian inference method that integrates experimental information with prior knowledge of the system and deals with all sources of uncertainty and errors as well as with system heterogeneity. Furthermore, metainference can be implemented using the metadynamics approach, which enables the computational study of complex biological systems requiring extensive conformational sampling. In this chapter, we provide a step-by-step guide to perform and analyse metadynamic metainference simulations using the ISDB module of the open-source PLUMED library, as well as a series of practical tips to avoid common mistakes. Specifically, we will guide the reader in the process of learning how to model the structural ensemble of a small disordered peptide by combining state-of-the-art molecular mechanics force fields with nuclear magnetic resonance data, including chemical shifts, scalar couplings and residual dipolar couplings.Comment: 49 pages, 9 figure

Detection of the mosquito-borne flaviviruses, West Nile, Dengue, Saint Louis Encephalitis, Ilheus, Bussuquara, and Yellow Fever in free-ranging black howlers (Alouatta caraya) of Northeastern Argentina

Several medically important mosquito-borne flaviviruses have been detected in Argentina in recent years: Dengue (DENV), St. Louis encephalitis (SLEV), West Nile (WNV) and Yellow Fever (YFV) viruses. Evidence of Bussuquara virus (BSQV) and Ilheus virus (ILHV) activity were found, but they have not been associated with human disease. Non-human primates can act as important hosts in the natural cycle of flaviviruses and serological studies can lead to improved understanding of virus circulation dynamics and host susceptibility. From July–August 2010, we conducted serological and molecular surveys in free–ranging black howlers (Alouatta caraya) captured in northeastern Argentina. We used 90% plaque-reduction neutralization tests (PRNT90) to analyze 108 serum samples for antibodies to WNV, SLEV, YFV, DENV (serotypes 1and 3), ILHV, and BSQV. Virus genome detection was performed using generic reverse transcription (RT)-nested PCR to identify flaviviruses in 51 antibody-negative animals. Seventy animals had antibodies for one or more flaviviruses for a total antibody prevalence of 64.8% (70/108). Monotypic (13/70, 19%) and heterotypic (27/70, 39%) patterns were differentiated. Specific neutralizing antibodies against WNV, SLEV, DENV-1, DENV-3, ILHV, and BSQV were found. Unexpectedly, the highest flavivirus antibody prevalence detected was to WNV with 9 (8.33%) monotypic responses. All samples tested by (RT)-nested PCR were negative for viral genome. This is the first detection of WNV-specific antibodies in black howlers from Argentina and the first report in free-ranging non-human primates from Latin-American countries. Given that no animals had specific neutralizing antibodies to YFV, our results suggest that the study population remains susceptible to YFV. Monitoring of these agents should be strengthened to detect the establishment of sylvatic cycles of flaviviruses in America and evaluate risks to wildlife and human health.Fil: Morales, Maria Alejandra. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbran". Instituto Nacional de Enfermedades Virales Humanas; ArgentinaFil: Fabbri, Cintia M.. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbran". Instituto Nacional de Enfermedades Virales Humanas; ArgentinaFil: Zunino, Gabriel Eduardo. Universidad Nacional de General Sarmiento. Instituto del Conurbano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kowalewski, Miguel Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia". Estación Biológica de Usos Múltiples (Sede Corrientes); ArgentinaFil: Luppo, Victoria C.. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbran". Instituto Nacional de Enfermedades Virales Humanas; ArgentinaFil: Enría, Delia A.. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbran". Instituto Nacional de Enfermedades Virales Humanas; ArgentinaFil: Levis, Silvana C.. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbran". Instituto Nacional de Enfermedades Virales Humanas; ArgentinaFil: Calderón, Gladys Ethel. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbran". Instituto Nacional de Enfermedades Virales Humanas; Argentin