A Comparison of the Clinical and Molecular Diagnosis of Herpes Simplex Keratitis

Purpose: To compare the clinical and molecular diagnoses of Herpes Simplex Keratitis (HSK). Materials and Methods: Conjunctival swabs (after fluorescein and anaesthetic wash out) and detailed questionnaire data were obtained from 146 participants. Corneal rims and conjunctival epithelial cells were infected with Herpes Simplex Virus (HSV) type 1 or HSV2 and supernatant collected. HSV1;HSV2;Varicella Zoster Virus (VZV) and Adenovirus (ADV) DNA was assessed using two real time Polymerase Chain Reaction (PCR) methods. Results: Of the 146 participants recruited, 54 were clinically diagnosed with typical epithelial lesions and 38 with atypical epithelial lesions, 17 with old inactive HSK and 37 healthy volunteers. HSV1 DNA was detected in 28 (30%) of the 92 participants with clinically suspect HSK. Patients who presented with typical epithelial lesions had a higher positive rate (46%) than those who presented with atypical type lesions (8%), when using primers against the Glycoprotein (Gp) G region of the virus. When the same samples were retested with primers against the GpB region, the positive rate for the typical and atypical cases increased to 52% and 11% respectively. Antiviral use at the time of sampling reduced the rate of PCR positivity by 20% (p < 0.05). ADV DNA was detected in 6% of the typical cases and 8% of the atypical cases. All control participants with no history of HSK were negative for HSV1 DNA. Sample quantity was confirmed by testing for housekeeping control genes, beta-actin and beta-2 macroglobulin. PCR results from in vitro control investigations of HSV1 and 2 infected corneal rims and conjunctival epithelial cells were 100% positive for infected and 100% negative for uninfected samples when assessed using both PCR methods. Conclusions: Clinical diagnosis of typical HSK is not always confirmed by PCR. Concomitant use of an antiviral reduces levels of PCR positivity. Given this and the findings that other ocular surface pathogens may mimic HSK pathology, and that choice of gene amplification region can also affect accurate detection of HSV1 by PCR, we propose the use of a multiplex assay. This would perform PCR using primers spanning a number of different regions within one gene and would also target a number of different viral genes to ensure potentially different HSV1 viral strains or other viruses do not affect the test and lead to disagreements between the clinical and molecular diagnosis of HSK. From these findings, this paper proposes a clinical supportive algorithmic guide to manage such disagreements.

Distinguishing normal brain aging from the development of Alzheimer＇s disease：inflammation,insulin signaling and cognition

As populations age, prevalence of Alzheimer＇s disease（AD） is rising. Over 100 years of research has provided valuable insights into the pathophysiology of the disease, for which age is the principal risk factor. However, in recent years, a multitude of clinical trial failures has led to pharmaceutical corporations becoming more and more unwilling to support drug development in AD. It is possible that dependence on the amyloid cascade hypothesis as a guide for preclinical research and drug discovery is part of the problem. Accumulating evidence suggests that amyloid plaques and tau tangles are evident in non-demented individuals and that reducing or clearing these lesions does not always result in clinical improvement. Normal aging is associated with pathologies and cognitive decline that are similar to those observed in AD, making differentiation of AD-related cognitive decline and neuropathology challenging. In this mini-review, we discuss the difficulties with discerning normal, age-related cognitive decline with that related to AD. We also discuss some neuropathological features of AD and aging, including amyloid and tau pathology, synapse loss, inflammation and insulin signaling in the brain, with a view to highlighting cognitive or neuropathological markers that distinguish AD from normal aging. It is hoped that this review will help to bolster future preclinical research and support the development of clinical tools and therapeutics for AD.

Re-Thinking Biology—I. Maxwell’s Demon and the Spontaneous Origin of Life

A hypothesis is advanced in which life began from a Darwinian selection among a diversification of molecular species containing the phosphate moiety which broke the constraints implicit in the Second Law of Thermodynamics, discussed famously by Schrodinger, by obtaining energy from specific infrared frequencies located in the phosphorus-oxygen vibration at a frequency around 1000 cm-1. We propose the source of this energy was from the internal conversion of solar broadband energy by the phosphate mineral Apatite, present at the bottom of a primitive biogenesis pond. In this scenario, life is re-defined as being hotter than its environment and as using its excess energy, supplied by infra-red conversion, to react with its molecular environment and pump itself up the “entropy slope” thereby;replication is through breakages of increasingly large phosphate containing biopolymers. The idea has implications for modern explanations of living systems.

Active Case Finding of Pulmonary Tuberculosis among Prison Inmates in Aba Federal Prison, Abia State, Nigeria

Background: Conditions in prisons favour rapid transmission of Mycobacterium tuberculosis and progression to tuberculosis (TB) disease, resulting in higher prevalence rates of TB in prisons than in the corresponding general population. However, in many developing countries with high TB burden, passive case-finding remains the usual approach to case detection of TB in prisons. On this premise, the Abia State TB Control Programme conducted a pilot study to assess the contribution of active case finding to tuberculosis control in Aba Federal Prison. Methods: The inmates were clinically screened and those with symptoms suggestive of TB cases were tested by sputum smear microscopy. Results: Out of the total number of 477 prison inmates present in the prison at the time of study, 449 (94.1%) were clinically screened for history of cough of 2 weeks’ duration;52 (10.42%) met the inclusion criteria for sputum smear microscopy. Eleven of the 52 (21.15%) tested for acid fast bacilli (AFB) by direct smear light microscopy were positive for AFB. One inmate was on anti-tuberculosis therapy;this with the 11 cases detected in the course of this study gave a total of 12 inmates of Aba prison with active pulmonary tuberculosis at the time of this study. This gives a minimum point prevalence rate of 2405 cases per 100,000 prison inmates. Four of the 11 prison cells had at least one smear positive case with 7 of the 11 cases concentrated in two cells. The age group of 25 - 34 years had the highest number of sputum positive cases. Conclusion: Active case-finding resulted in detection of 11 new cases of sputum positive tuberculosis (an increase in detection rate of 1100%) and the prevalence of sputum positive TB is very high (2405 cases per 100,000 prison inmates) in Aba prison. There is an urgent need to institute more effective TB case-finding and control in the prison.