Cryptococcus neoformans meningitis in a diabetic patient - the perils of an overzealous immune response: a case report

Uncontrolled diabetics are prone to infections due to numerous factors as the glucose-rich blood serves as an excellent media for growth. Cryptococcus neoformans is an opportunistic fungus that is an important cause of CNS infections among immunocompromised patients, but it has only sporadically been reported in non-HIV-positive persons. The presence of elevated pro-inflammatory cytokines and abnormalities in numerous systemic indicators of inflammation in diabetics makes it conceivable that diabetics mount an exaggerated immune response to C. neoformans (paradoxical to their defective immune state) leading to grave outcomes. We present a fatal case of C. neoformans meningitis in a diabetic patient which emphasizes the perils of an overzealous immune response

Discovery of molecular hydrogen in a high-velocity cloud of the Galactic halo

We report the discovery of molecular hydrogen absorption in a Galactic high-velocity cloud (HVC) in the direction of the Large Magellanic Cloud. For the same HVC we derive an iron abundance which is half of the solar value. Thus, all evidence points to a Galactic origin for high-velocity cloud complex in front of the LMC.Comment: Published in Nature, this week; 14 pages, 3 figure

The regulatory role of long-term depression in juvenile and adult mouse ocular dominance plasticity

The study of experience-dependent ocular dominance (OD) plasticity has greatly contributed to the understanding of visual development. During the critical period, preventing input from one eye results in a significant impairment of vision, and loss of cortical responsivity via the deprived eye. Residual ocular dominance plasticity has recently been observed in adulthood. Accumulating evidence suggests that OD plasticity involves N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD). Here we report that the administration of a selective LTD antagonist prevented the ocular dominance shift during the critical period. The NMDAR co-agonist D-serine facilitated adult visual cortical LTD and the OD shift in short-term monocularly deprived (MD) adult mice. When combined with reverse suture, D-serine proved effective in restoring a contralaterally-dominated visual input pattern in long-term MD mice. This work suggests LTD as a key mechanism in both juvenile and adult ocular dominance plasticity, and D-serine as a potential therapeutic in human amblyopic subjects

Teaching About Health Care Disparities in the Clinical Setting

Clinical teachers often observe interactions that may contribute to health care disparities, yet may hesitate to teach about them. A pedagogical model could help faculty structure teaching about health care disparities in the clinical setting, but to our knowledge, none have been adapted for this purpose. In this paper, we adapt an established model, Time-Effective Strategies for Teaching (TEST), to the teaching of health care disparities. We use several case scenarios to illustrate the core components of the model: diagnose the learner, teach rapidly to the learner’s need, and provide feedback. The TEST model is straightforward, easy to use, and enables the incorporation of teaching about health care disparities into routine clinical teaching

Estimated GFR reporting is not sufficient to allow detection of chronic kidney disease in an Italian regional hospital

<p>Abstract</p> <p>Background</p> <p>Chronic kidney disease (CKD) is an emerging worldwide problem. The lack of attention paid to kidney disease is well known and has been described in previous publications. However, little is known about the magnitude of the problem in highly specialized hospitals where serum creatinine values are used to estimate GFR values.</p> <p>Methods</p> <p>We performed a cross-sectional evaluation of hospitalized adult patients who were admitted to the medical or surgical department of Santa Maria della Misericordia Hospital in 2007. Information regarding admissions was derived from a database. Our goal was to assess the prevalence of CKD (defined as an estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m²) and detection of CKD using diagnostic codes (Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]). To reduce the impact of acute renal failure on the study, the last eGFR obtained during hospitalization was the value used for analysis, and intensive care and nephrology unit admissions were excluded. We also excluded patients who had ICD-9-CM codes for renal replacement therapy, acute renal failure, and contrast administration listed as discharge diagnoses.</p> <p>Results</p> <p>Of the 18,412 patients included in the study, 4,748 (25.8%) had reduced eGFRs, falling into the category of Kidney Disease Outcomes Quality Initiative (KDOQI) stage 3 (or higher) CKD. However, the diagnosis of CKD was only reported in 19% of these patients (904/4,748). It is therefore evident that there was a "gray area" corresponding to stage 3 CKD (eGFR 30-59 ml/min), in which most CKD diagnoses are missed. The ICD-9 code sensitivity for detecting CKD was significantly higher in patients with diabetes, hypertension, and cardiovascular disease (26.8%, 22.2%, and 23.7%, respectively) than in subjects without diabetes, hypertension, or cardiovascular disease (p < 0.001), but these values are low when the widely described relationship between such comorbidities and CKD is considered.</p> <p>Conclusion</p> <p>Although CKD was common in this patient population at a large inpatient regional hospital, the low rates of CKD detection emphasize the primary role nephrologists must play in continued medical education, and the need for ongoing efforts to train physicians (particularly primary care providers) regarding eGFR interpretation and systematic screening for CKD in high-risk patients (i.e., the elderly, diabetics, hypertensives, and patients with CV disease).</p

The clinical utility of the continuous performance test and objective measures of activity for diagnosing and monitoring ADHD in children: a systematic review

Attention deficit hyperactivity disorder (ADHD) is typically diagnosed using clinical observation and subjective informant reports. Once children commence ADHD medication, robust monitoring is required to detect partial or non-responses. The extent to which neuropsychological continuous performance tests (CPTs) and objective measures of activity can clinically aid the assessment and titration process in ADHD is not fully understood. This review describes the current evidence base for the use of CPTs and objectively measured activity to support the diagnostic procedure and medication management for children with ADHD. Four databases (PsycINFO, Medline, Allied and Complementary Medicine (AMED) and PsycARTICLES) were systematically searched to understand the current evidence base for: (1) the use of CPTs to aid clinical assessment of ADHD; (2) the use of CPTs to aid medication management; (3) the clinical utility of objective measures of activity in ADHD. Sixty relevant articles were identified. The search revealed six commercially available CPTs that had been reported on for their clinical use. There were mixed findings with regard to the use of CPTs to assess and manage medication, with contrasting evidence on their ability to support clinical decision making. There was a strong evidence base for the use of objective measures of activity to aid ADHD/non-ADHD group differentiation, which appears sensitive to medication effects and would also benefit from further research on their clinical utility. The findings suggest that combining CPTs and an objective measure of activity may be particularly useful as a clinical tool and worthy of further pursuit

Soluble CD4 and CD4-Mimetic Compounds Inhibit HIV-1 Infection by Induction of a Short-Lived Activated State

Binding to the CD4 receptor induces conformational changes in the human immunodeficiency virus (HIV-1) gp120 exterior envelope glycoprotein. These changes allow gp120 to bind the coreceptor, either CCR5 or CXCR4, and prime the gp41 transmembrane envelope glycoprotein to mediate virus–cell membrane fusion and virus entry. Soluble forms of CD4 (sCD4) and small-molecule CD4 mimics (here exemplified by JRC-II-191) also induce these conformational changes in the HIV-1 envelope glycoproteins, but typically inhibit HIV-1 entry into CD4-expressing cells. To investigate the mechanism of inhibition, we monitored at high temporal resolution inhibitor-induced changes in the conformation and functional competence of the HIV-1 envelope glycoproteins that immediately follow engagement of the soluble CD4 mimics. Both sCD4 and JRC-II-191 efficiently activated the envelope glycoproteins to mediate infection of cells lacking CD4, in a manner dependent on coreceptor affinity and density. This activated state, however, was transient and was followed by spontaneous and apparently irreversible changes of conformation and by loss of functional competence. The longevity of the activated intermediate depended on temperature and the particular HIV-1 strain, but was indistinguishable for sCD4 and JRC-II-191; by contrast, the activated intermediate induced by cell-surface CD4 was relatively long-lived. The inactivating effects of these activation-based inhibitors predominantly affected cell-free virus, whereas virus that was prebound to the target cell surface was mainly activated, infecting the cells even at high concentrations of the CD4 analogue. These results demonstrate the ability of soluble CD4 mimics to inactivate HIV-1 by prematurely triggering active but transient intermediate states of the envelope glycoproteins. This novel strategy for inhibition may be generally applicable to high–potential-energy viral entry machines that are normally activated by receptor binding