Complex Dynamics of Adaptation in a Nonaxenic Microcystis Culture: 2. Computer Simulation of Dinitrophenol Effects

A hypothesis was modeled to account for complex 20-day dynamics in a culture of blue-green algae Microcystis and heterotrophic bacteria exposed to 2,4-dinitrophenol (DNP). In trials with little or no added DNP, a limiting factor (light or CO₂) may cause algal density to fluctuate after 14 days of increase. Such factors may be unimportant at levels of DNP that restrict photosynthesis. Bacterial growth may be limited by organic substrate, and bacteria may be more resistant to DNP than blue-green algae. Hence, at intermediate levels of DNP, substrate provided by increased algal death stimulates bacterial growth more than DNP retards it, causing a bacterial peak. Sorption of DNP to cells may cause the DNP decline. Greater growth and slower DNP decline in experiments with preexposed organisms indicate lower DNP sorption affinity in preexposed cells. Bacterial assimilation of DNP-containing substrate may cause the reappearance of DNP. The model reproduced the fluctuation in algal density after growth was limited and better growth and lower DNP decline with preexposed organisms. Reappearance of DNP occurred, but was not obvious. Bacterial dynamics were least well reproduced. Changes in bacterial constants most affected output. Despite model inadequacies, probable aspects of toxicant action in nature have been revealed. Ecological relationships among populations of different species and genetic differences among individuals may have led to lower than expected toxicity, adaptation, and even growth stimulation. Responses of single species tested in isolation may be inadequate to predict toxicant impact.     

Mobile Digital Fluorescence Microscopy for Diagnosis of Tuberculosis

Access to sputum smear microscopy in high-tuberculosis (TB)-burden regions is limited by a scarcity of microscopes and experienced technicians. We evaluated the accuracy of CellScope, a novel digital fluorescence microscope that may expand access to microscopy. The study utilized smear microscopy slides prepared from sputum specimens submitted by consecutive adults with ≥2 weeks of cough who were admitted to Mulago Hospital (Kampala, Uganda). Conventional light-emitting diode (LED) fluorescence microscopy (FM) and mycobacterial culture were performed by experienced technicians. Two U.S.-based postgraduate researchers without prior microscopy experience restained, imaged, and interpreted the slides using CellScope. We assessed whether sensitivity and specificity of CellScope-based LED FM was noninferior to conventional LED FM by using a preselected margin of inferiority of 15%. Of 525 patients included, 72% were HIV seropositive and 39% had culture-confirmed TB. The proportions of positive results were similar with CellScope and conventional LED FM (34% versus 32%, respectively; P = 0.32), and agreement was substantial. CellScope accuracy was within the noninferiority margin for both sensitivity (63% versus 70%; difference, −7%; 95% confidence interval [CI], −13% to −1%) and specificity (85% versus 92%; difference, −7%; 95% CI, −12% to −3%). A subanalysis of 43 slides evaluated by each CellScope reader found substantial interreader reliability (custom-weighted kappa, 0.65) and variable intrareader reliability (custom-weighted kappa, 0.11 versus 0.48). CellScope offers promise for expanding microscopy services. Future studies should evaluate the device when operated by health workers in low-resource settings, the feasibility of image transmission and analysis by experienced microscopists, and the accuracy of automated image analysis algorithms.     

Photodermatitis with minimal inflammatory infiltrate: clinical inflammatory conditions with discordant histologic findings

Dermatoses associated with cutaneous photosensitivity are a group of photodistributed skin eruptions caused or exacerbated by light. Multiple clinical variants of photosensitive dermatoses have been characterized including polymorphous light eruption, chronic actinic dermatitis, solar urticaria, phototoxic and photoallergic dermatitis, reticular erythematous mucinosis, acute cutaneous lupus erythematosus, and dermatomyositis. As there may be significant overlap among the clinical presentation of these conditions, the specific diagnosis of individual photodermatosis relies heavily on characteristic histopathologic features. We present here 5 cases of photodistributed eruptions with virtual absence of histologic epidermal changes and dermal inflammation, yet all were described clinically as being "inflammatory" and erythematous. All cases of this "pauci-inflammatory photodermatitis" presented with photodistributed bright red macular erythema or slightly indurated plaques that developed over a period of weeks to months and clinically resembled photoallergic or phototoxic drug reactions or polymorphous light eruption. Microscopically, however, only very sparse dermal lymphocytic infiltrate was noted with no or minimal epidermal changes. To our knowledge, the observation of clinically evident photodistributed dermatoses that demonstrate such minimal histopathologic findings has not been reported. Clinicians and histologists should be aware of the disparity that may be encountered in this setting, as the clinical features are usually far more impressive than those seen histologically.     

Downregulated Expression of Ly-6-ThB on Developing T Cells Marks CD4+CD8+ Subset Undergoing Selection in the Thymus

Interaction of TCRs on CD4⁺CD8⁺ immature T cell with MHC-peptide complexes on stromal cells is required for positive and negative selection in the thymus. Identification and characterization of a subpopulation of CD4⁺CD8⁺ thymocytes undergoing selection in the thymus will aid in understanding the mechanisms underlying lineage commitment and thymic selection. Herein, we describe the expression of Ly-6 ThB on developing thymocytes. The majority of CD4⁺CD8⁺ thymocytes express Ly-6 ThB at high levels. Its expression is downregulated in a subset of CD4⁺CD8⁺ thymocytes as well as in mature CD4⁺CD8^- and CD4^-CD8⁺ T cells. More importantly, interaction of TCR/coreceptor with the self-MHC-peptide contributes to the downregulation of ThB expression on developing thymocytes. These findings indicate that downregulation of ThB on CD4⁺CD8⁺ thymocytes identifies a unique subset (CD4+CD8+ThB^neg–low) of thymocytes that has received the initial signals for thymic selection but have not yet downregulated the CD4 and CD8 cell surface expression. In addition, these results also indicate that a high frequency (Ÿ20–40%) of CD4⁺CD8⁺ immature thymocytes receive these initial signals during thymic selection.     

In vitro generated Rhnull red cells recapitulate the in vivo deficiency: A model for rare blood group phenotypes and erythroid membrane disorders

Lentiviral modification combined with ex vivo erythroid differentiation was used to stably inhibit RhAG expression, a critical component of the Rh(rhesus) membrane complex defective in the Rh_null syndrome. The cultured red cells generated recapitulate the major alterations of native Rh_null cells regarding antigen expression, membrane deformability, and gas transport function, providing the proof of principle for their use as model of Rh_null syndrome and to investigate Rh complex biogenesis in human primary erythroid cells. Using this model, we were able to reveal for the first time that RhAG extinction alone is sufficient to explain ICAM‐4 and CD47 loss observed on native Rh_null RBCs. Together with the effects of RhAG forced expression in Rh_null progenitors, this strongly strengthens the hypothesis that RhAG is critical to Rh complex formation. The strategy is also promising for diagnosis purpose in order to overcome the supply from rare blood donors and is applicable to other erythroid defects and rare phenotypes, providing models to dissect membrane biogenesis of multicomplex proteins in erythroid cells, with potential clinical applications in transfusion medicine. Am. J. Hematol. 88:343–349, 2013. © 2013 Wiley Periodicals, Inc.     

How Well Do We Report on Compensation Systems in Studies of Return to Work: A Systematic Review

Purpose Occupational injury and work-related disability is a significant public health problem. For published research to provide a collective knowledge base for return to work (RTW) policy and practice, features of the compensation system relevant to the research must be described clearly. The level of the reporting on compensation system features is yet to be established. The aim of the present study was to synthesize the evidence for the reporting on compensation systems in prognostic studies of RTW following work-related injuries. Methods A systematic review of the literature was conducted. Ovid Medline and EMBASE were searched for studies published 1996–2011. Included studies were prognostic studies of RTW or work disability following work-related acute traumatic injuries. Results The initial search yielded 952 articles; 37 articles fulfilled the inclusion criteria. The majority of studies were based on clinical practice; eight studies were based on administrative data. Only two studies reported seven or more compensation features and two studies reported four to six. The majority of studies (19/37) did not report on any aspect of the compensation system that study participants were interacting with. The most common information reported was the extent of coverage at the population level (7/37) and the availability of wage replacement entitlements (7/37). The name of the compensation system was provided in 5 studies. Conclusions Overall reporting on compensation systems in prognostic studies of RTW needs to be improved if research evidence is to inform policy and practice. Compensation system features that could be reported are provided.