Update and Advances on Post-dural Puncture Headache.

This document provides an overview of post-dural puncture headache (PDPH), covering its historical perspective, anatomy and physiology of cerebrospinal fluid (CSF), pathophysiology, risk factors, diagnosis, and treatment options. PDPH is a common complication of dural puncture, characterized by a postural headache due to CSF leakage. The understanding of CSF and dural anatomy has evolved over time, leading to advancements in diagnosing and managing PDPH. Treatment options range from conservative measures to epidural blood patch, intrathecal catheter, and regional techniques like sphenopalatine ganglion block and greater occipital nerve block. Further research is needed to optimize treatment approaches and improve patient outcomes.

Neuro-ophthalmological manifestations of sarcoidosis.

Neuro-sarcoidosis has important ophthalmic and neuro-ophthalmic manifestations. Sarcoidosis most commonly affects the uveal tract (iris, ciliary body, and choroid) however the optic nerve is commonly involved. Sarcoid related optic neuritis is an important differential diagnosis in optic neuritis especially in atypical presentations. The use of multimodal imaging techniques available in the ophthalmic setting can enable the detection of choroidal or optic nerve granulomas and aid the diagnosis. Efferent manifestations of neuro-sarcoidosis are broad and can range from isolated cranial neuropathies or multiple as well as pupil abnormalities. Currently to date there are no diagnostic framework to assist in the diagnosis of ophthalmic manifestations in neuro-sarcoidosis in the absence of a tissue biopsy.

Impact on patient management of non-mydriatic fundus photography compared to direct ophthalmoscopy in a regional Australian emergency department.

OBJECTIVE: To investigate the management impact of non-mydriatic fundus photography (NMFP) implementation for appropriate ED patients; compare the diagnostic accuracy of direct ophthalmoscopy (DO) and NMFP, and determine the prevalence of fundus pathology in a regional Australian ED. METHODS: This before/after crossover study prospectively enrolled patients presenting with headache, neurological deficit, visual disturbance and/or hypertensive urgency. Patients received DO examination, then separate NMFP examination. Emergency clinicians (ECs) were surveyed on their patient management plans following both DO examination and NMFP imaging. Telemedicine review of NMFP images was performed by an ophthalmologist within 48 h, and any additional management changes were documented. RESULTS: The use of NMFP influenced changes in management in 52 (39%) of 133 enrolled patients (95% confidence interval 31-48%). Of these, 65% were escalations of management due to acute fundus pathology, while 35% were de-escalating changes following normal fundus findings. ECs diagnostic accuracy for acute fundus pathology improved from 0% to 29% sensitivity, and 59% to 84% specificity using DO and NMFP respectively, and telemedicine registrar review increased this to 50% sensitivity and 86% specificity. The period prevalence of acute fundus pathology was 10.5% (95% confidence interval 6-17%). CONCLUSION: The addition of NMFP images can significantly impact the management of ED patients requiring fundus examination, facilitating expedited and optimised patient care. NMFP improves ECs diagnostic acumen for fundus pathology over DO examination and telehealth specialist review is important for diagnostic accuracy. There is a clinically important prevalence of fundus pathology in this regional ED setting.

Endophthalmitis: Changes in Presentation, Management and the Role of Early Vitrectomy.

Endophthalmitis is a sight-threatening condition, and its timely and appropriate management is essential in preventing permanent vision loss. Recent changes in clinical practice in endophthalmitis and advances in modern vitreoretinal surgery may limit the applicability of established randomised clinical trial evidence to current management. This review discusses the epidemiology, pathophysiology, changing patient presentation, diagnosis and advances in the management of endophthalmitis, presenting the existing literature on this topic and results from Sydney Eye Hospital.

Intravitreal anti-vascular endothelial growth factor versus panretinal LASER photocoagulation for proliferative diabetic retinopathy: a systematic review and meta-analysis.

OBJECTIVE: To systematically review and perform a meta-analysis on the available evidence for anti-vascular endothelial growth factor (anti-VEGF) monotherapy versus panretinal photocoagulation (PRP) for proliferative diabetic retinopathy (PDR). DESIGN: Systematic review and meta-analysis PARTICIPANTS: Randomized clinical trials included participants ≥18 years old with clinical or angiographic evidence of PDR. Interventions included were anti-VEGF monotherapy and PRP. Excluded studies were those with potentially biased treatment allocation and those offering combination therapies. METHODS: The primary outcome was mean change in best-corrected visual acuity. Secondary outcomes were the proportion of patients developing severe (<6/60) or moderate (6/24-6/60) vision loss, rates of vitrectomy or vitreous hemorrhage, worsening macula edema, and reduced visual field indices. RESULTS: Five studies of varying quality met the inclusion criteria (n = 632). The anti-VEGF intervention arm had a mean difference of -0.08 logMAR or 4 Early Treatment Diabetic Retinopathy Study (EDTRS) letters gained (p = 0.02) when compared with PRP at 12 months. The difference in rates of vitrectomy and vitreous hemorrhage favoured anti-VEGF over PRP (risk difference [RD] -0.10, p = < 0.001 and RD -0.10, p = 0.003 respectively). CONCLUSIONS: This meta-analysis of the available evidence in patients with early PDR demonstrates a potential benefit for anti-VEGF over PRP alone. However, these benefits must be weighed against the relative costs of treatment and the potential risks of loss to follow-up.

Offline Learning with a Selection Hyper-Heuristic: An Application to Water Distribution Network Optimisation.

A sequence-based selection hyper-heuristic with online learning is used to optimise 12 water distribution networks of varying sizes. The hyper-heuristic results are compared with those produced by five multiobjective evolutionary algorithms. The comparison demonstrates that the hyper-heuristic is a computationally efficient alternative to a multiobjective evolutionary algorithm. An offline learning algorithm is used to enhance the optimisation performance of the hyper-heuristic. The optimisation results of the offline trained hyper-heuristic are analysed statistically, and a new offline learning methodology is proposed. The new methodology is evaluated, and shown to produce an improvement in performance on each of the 12 networks. Finally, it is demonstrated that offline learning can be usefully transferred from small, computationally inexpensive problems, to larger computationally expensive ones, and that the improvement in optimisation performance is statistically significant, with 99% confidence.

Ocular Toxoplasmosis in a Tertiary Referral Center in Sydney Australia-Clinical Features, Treatment, and Prognosis.

PURPOSE: The aim of this study was to provide a retrospective analysis of the presentation, demographics, and treatment regimens for ocular toxoplasmosis at a large tertiary referral uveitis center. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 48 patients with ocular toxoplasmosis who presented to Sydney Eye Hospital participated in this study. METHODS: This is a retrospective review of patient files who presented to Sydney Eye Hospital between 2007 and 2016 with clinical features consistent with ocular toxoplasmosis. Baseline risk factors and treatment details were recorded and analyzed. Main outcome measures were visual acuity and relapse rate compared with other studies in ocular toxoplasmosis. RESULTS: The median age was 35.5 (interquartile range 21-50) with 30 (60%) patients having no previous symptomatic episodes or evidence of chorioretinal scarring. Visual acuity at presentation was 0.51 or 6/19 (SE 0.096) and at follow-up 0.31 or 6/12 (SE 0.094). Nine patients experienced a recurrence during the period of observation with median time to recurrence 2.2 years (SE 0.45) and the relapse rate was 0.09/person-years. Location of lesion was predominantly within the vascular arcades (n = 44) with macular involvement in 9 patients. Most patients received clindamycin therapy (n = 34) with pyrimethamine and sulfadiazine was used for those with macula involvement. CONCLUSIONS: Patients with ocular toxoplasmosis had fewer recurrences compared with other published series and had better visual recovery. The majority of patients received clindamycin and oral prednisolone which were well tolerated with pyrimethazine and sulfadiazine reserved for those with macula-involving disease.

Optic Perineuritis Due to Tuberculosis.

A 30-year-old man experienced subacute peripheral visual field loss with preserved central vision in his right eye. He was diagnosed with optic perineuritis due to tuberculosis. Optic perineuritis is an uncommon disorder and, at times, can be difficult to distinguish from optic neuritis. The differentiation can have significant impact on diagnostic testing and patient management.

Post-surgical versus post-intravitreal injection endophthalmitis: changing patterns in causative flora.

IMPORTANCE: Endophthalmitis is a serious complication of intraocular procedures: knowledge of its causative organisms and outcomes may guide prevention and treatment. BACKGROUND: To determine the outcomes and spectrum of causative organisms in acute post-procedural endophthalmitis. DESIGN: A retrospective observational case series performed at a tertiary referral hospital during the period 1 July 2012 to 31 July 2017. PARTICIPANTS: Two hundred and forty-eight patients diagnosed with acute (≤ 6 weeks post-inciting event) endophthalmitis. METHODS: Chart review of microbiological and clinical data. MAIN OUTCOME MEASURES: The main outcome measure was odds of any improvement in visual acuity (3 months versus presentation). Secondary outcomes included causative organism, likelihood of vitrectomy and likelihood of evisceration. RESULTS: One hundred and ninty cases were post-cataract surgery or post-intravitreal injection (49 and 141, respectively). Causative organisms were identified in 45% of post-cataract surgery and 54% of post-injection cases (OR = 0.69; P = 0.61). Staphylococcus epidermidis was the most frequent causative organism. Streptococcus species accounted for 32% of post-surgical and 7% of culture-positive post-injection cases (OR = 6.63; P = 0.02). At 3 months, 81% of post-surgical and 84% of post-injection cases had improved BCVA over presentation (OR 0.59; P = 0.61). CONCLUSIONS AND RELEVANCE: S. epidermidis is the most common causative organism. In contrast to other studies, we did not find evidence for an increased odds of Streptococcus spp. endophthalmitis following intravitreal injection. This may in turn reflect guideline-driven changes in practice.

Adalimumab for the treatment of refractory active and inactive non-infectious uveitis.

BACKGROUND/AIMS: To compare the efficacy of adalimumab in eyes with active and inactive non-infectious uveitis in the real-world setting. METHODS: Multicentre, retrospective, chart review of patients with refractory non-infectious uveitis treated with adalimumab. Main outcome measures included reduction of prednisolone dose, ability to taper immunosuppressives and a composite endpoint of treatment failure encompassing active inflammatory chorioretinal or retinal vascular lesions, intraocular inflammation grade and visual acuity. RESULTS: Thirty-seven eyes of 22 patients were studied. Mean follow-up was 20.1 months (median: 13). Most had either posterior or panuveitis (n=12, 55%). Mean duration of uveitis at baseline was 83.2 months (median: 61), where the majority (n=15, 68%) had already been treated with two or more conventional immunosuppressive agents in addition to prednisolone. Oral prednisolone was reduced to ≤10 mg/day in 9 of 12 patients (75%) by 6 weeks. At 6 months of therapy, nine (90%) of the active eyes achieved a 2-step improvement in anterior chamber inflammation, with six (60%) demonstrating a similar improvement in vitreous haze grade. Almost all (n=17, 94%) of the initially inactive eyes maintained clinical quiescence at this time point. The incidence rate of treatment failure during follow-up was 88 per 100 eye-years for the active eyes and 24 per 100 eye-years for the initially inactive eyes. There were no serious adverse effects. CONCLUSION: Adalimumab appears to reduce the corticosteroid burden in active and inactive non-infectious uveitis in the real-world setting. Inflammatory activity at the time of adalimumab commencement may determine long-term treatment success.

Treatment of bipolar depression with minocycline and/or aspirin: an adaptive, 2×2 double-blind, randomized, placebo-controlled, phase IIA clinical trial.

Given evidence of chronic inflammation in bipolar disorder (BD), we tested the efficacy of aspirin and minocycline as augmentation therapy for bipolar depression. Ninety-nine depressed outpatients with BD were enrolled in a 6 week, double-blind, placebo-controlled trial, and randomized to one of four groups: active minocycline (100 mg b.i.d.) + active aspirin (81 mg b.i.d.) (M + A); active minocycline + placebo aspirin (M + P); placebo-minocycline + active aspirin (A + P); and placebo-minocycline + placebo aspirin (P + P). A blinded interim analysis mid-way through the study led to the dropping of the M + P and A + P arms from further enrollment giving numbers per group who were included in the final analysis of: 30 (M + A), 18 (M + P), 19 (A + P), and 28 (P + P). When the study started, there were three primary outcome measures. Based on the results of the interim analysis, the primary outcome variable, response to treatment as defined by >50% decrease in Montgomery-Äsberg Depression Rating Scale (MADRS) score was maintained. The other two (i.e., the change in mean MADRS score from baseline to end of study and the remission rate, with remission being defined as a score of <11 on the MADRS) were reduced to exploratory outcome measures because the interim analysis indicated that the study was adequately powered to test differences in response rate but not the mean change in MADRS scores or remission rates. CRP and IL-6 were assayed to measure inflammation. Urinary thromboxane B2 (11-D-TXB2) concentrations, which were significantly increased at baseline in the combined BD sample (n = 90) vs. a healthy control group (n = 27), served as an indirect marker of cyclooxygenase (COX) activity. In a two-group analysis, the M + A group showed a greater response rate than the P + P group (p(one-tailed) = 0.034, OR = 2.93, NNT = 4.7). When all four arms were included in the analysis, there was a main effect of aspirin on treatment response that was driven by both the M + A and the A + P groups (p(two-tailed) = 0.019, OR = 3.67, NNT = 4.0). Additionally, there was a significant 3-way interaction between aspirin, minocycline, and IL-6, indicating that response to minocycline was significantly greater in participants in the M + P group with higher IL-6 concentrations. Further, participants in the M + P group who responded to treatment had significantly greater decreases in IL-6 levels between baseline and visit 7 vs. non-responders. Regarding the exploratory outcomes, there was a main effect for aspirin on the remission rate (χ12 = 4.14, p(2t) = 0.04, OR = 2.52, NNT = 8.0). There was no significant main effect of aspirin or minocycline on the mean change in MADRS score across visits. Aspirin and minocycline may be efficacious adjunctive treatments for bipolar depression. Given their potential import, additional studies to confirm and extend these findings are warranted.

Phenylethanolamine N-methyltransferase gene expression in PC12 cells exposed to intermittent hypoxia.

Epidemiological studies show a strong correlation between Obstructive Sleep Apnea (OSA) and cardiovascular disorders. OSA patients experience intermittent hypoxia (IH), characterized by brief, but recurring episodes of cessation in breathing. These patients have higher levels of circulating catecholamines and an increased incidence of hypertension; however the mechanisms defining this association are not clearly established. Genetic linkage studies have associated the phenylethanolamine N-methyltransferase (PNMT) gene to the development of hypertension. PNMT, the terminal enzyme in the catecholamine biosynthetic pathway, directly responsible for adrenaline synthesis, is elevated in hypertensive animals. Recent studies utilizing PC12 cells show an increase in the expression of PNMT and its regulatory transcription factors when exposed to continuous hypoxia. The current study examined the regulation of PNMT under conditions of IH. The mRNA of PNMT was analyzed to assess if the regulation of PNMT expression entails alternative splicing. The mRNA and protein of transcription factors HIF1α, Egr-1, GR, and Sp1, were analyzed to assess the cellular pathways involved in regulating PNMT expression. A PNMT promoter-driven luciferase assay was performed to evaluate promoter activity under IH. Preliminary results lay an antecedent for the regulation of PNMT by IH conceivably via an altered regulation of its transcription factors and establish a possible role for PNMT in IH mediated hypertension in OSA patients.

HLA-B27 Anterior Uveitis: Immunology and Immunopathology.

Acute anterior uveitis (AAU) is the commonest type of uveitis and HLA-B27 AAU is the most frequently recognized type of acute anterior uveitis and anterior uveitis overall. Recent evidence indicates that acute anterior uveitis is a heterogenous disease, is polygenic and is frequently associated with the spondyloarthropathies (SpA). Studies of patients with AAU and animal models of disease indicate a role for innate immunity, the IL-23 cytokine pathway and exogenous factors, in the pathogenesis of both SpA and acute anterior uveitis. Recently described genetic associations cluster around immunologic pathways, including the IL-17 and IL-23 pathways, antigen processing and presentation, and lymphocyte development and activation. Patients with ankylosing spondylitis (AS) and AAU share other genetic markers, such as ERAP-1, which show strong evidence of gene-gene interaction and point to new mechanisms of disease pathogenesis. These observations have major implications for understanding the pathogenesis of HLA-B27 diseases, such as AAU, and may lead to the development of more specific therapy for AAU. Received 6 January 2016; revised 6 February 2016; accepted 18 February 2016; published online 31 May 2016.

Roll-to-Roll Nanomanufacturing of Hybrid Nanostructures for Energy Storage Device Design.

A key limitation to the practical incorporation of nanostructured materials into emerging applications is the challenge of achieving low-cost, high throughput, and highly replicable scalable nanomanufacturing techniques to produce functional materials. Here, we report a benchtop roll-to-roll technique that builds upon the use of binary solutions of nanomaterials and liquid electrophoretic assembly to rapidly construct hybrid materials for battery design applications. We demonstrate surfactant-free hybrid mixtures of carbon nanotubes, silicon nanoparticles, MoS2 nanosheets, carbon nanohorns, and graphene nanoplatelets. Roll-to-roll electrophoretic assembly from these solutions enables the controlled fabrication of homogeneous coatings of these nanostructures that maintain chemical and physical properties defined by the synergistic combination of nanomaterials utilized without adverse effects of surfactants or impurities that typically limit liquid nanomanufacturing routes. To demonstrate the utility of this nanomanufacturing approach, we employed roll-to-roll electrophoretic processing to fabricate both positive and negative electrodes for lithium ion batteries in less than 30 s. The optimized full-cell battery, containing active materials of prelithiated silicon nanoparticles and MoS2 nanosheets, was assessed to exhibit energy densities of 167 Wh/kgcell(-1) and power densities of 9.6 kW/kgcell(-1).

Malignancy risk in patients with inflammatory eye disease treated with systemic immunosuppressive therapy: a tertiary referral cohort study.

OBJECTIVE: To ascertain whether patients on long-term systemic immunosuppressive therapy for inflammatory eye disease (IED) are at increased risk of malignancy. DESIGN: A single-center, retrospective cohort study. PARTICIPANTS: We included 190 adults with IED treated with corticosteroids only (n = 58) or systemic immunosuppression (n = 132) for ≥6 months between 1985 and 2007. Immunosuppressed patients were treated with antimetabolites, T-cell inhibitors, and/or alkylating agents. METHODS: Incident malignancies were ascertained by self-report and confirmed by medical record review. Multiple malignancies in a single patient were counted, except for nonmelanoma skin cancer (NMSC), where only the first was counted. Standardized incidence ratios (SIRs) were calculated by malignancy type. Cox regression models were used to compare malignancy incidence by treatment type. MAIN OUTCOME MEASURES: Risk of malignancy relative to the general population and within the cohort. RESULTS: During a median 7.34 years of follow-up, 25 malignancies were observed in 17 patients, namely, 2.10 per 100 person-years and 0.43 per 100 person-years in the immunosuppressed and corticosteroid only groups, respectively. In the immunosuppressed group, the most common malignancies were NMSC (n = 11) and non-Hodgkin's lymphoma (NHL; n = 4) and malignancy risk was significantly increased compared with the general population for any malignancy (SIR, 4.39; 95% CI, 2.78-6.59) and for any malignancy excluding NMSC (SIR, 4.16; 95% CI, 1.67-8.57). Significantly elevated SIRs were observed for NMSC and NHL in those treated with immunosuppressive agents. Compared with the corticosteroid treatment-only group, the immunosuppressed group was at an increased risk of any malignancy (adjusted hazard ratio, 4.36; 95% CI, 1.02-18.7), but not first malignancy (n = 17; adjusted hazard ratio, 2.56; 95% CI, 0.57-11.5). No cancer-related deaths were observed. CONCLUSIONS: Our findings suggest that patients with IED treated with systemic immunosuppressive therapy are at increased risk of malignancy; however, the increase in absolute risk was modest. The types of malignancies observed at excess risk are similar to those observed in solid organ transplant recipients and patients with autoimmune diseases treated with systemic immunosuppression. Immunosuppressive therapy remains an important treatment modality in IED; however, patients may benefit from targeted malignancy-prevention strategies and long-term clinical follow-up. These findings require validation by a prospective, long-term, population-based cohort study.

Genetic analysis of low BMI phenotype in the Utah Population Database.

The low body mass index (BMI) phenotype of less than 18.5 has been linked to medical and psychological morbidity as well as increased mortality risk. Although genetic factors have been shown to influence BMI across the entire BMI, the contribution of genetic factors to the low BMI phenotype is unclear. We hypothesized genetic factors would contribute to risk of a low BMI phenotype. To test this hypothesis, we conducted a genealogy data analysis using height and weight measurements from driver's license data from the Utah Population Data Base. The Genealogical Index of Familiality (GIF) test and relative risk in relatives were used to examine evidence for excess relatedness among individuals with the low BMI phenotype. The overall GIF test for excess relatedness in the low BMI phenotype showed a significant excess over expected (GIF 4.47 for all cases versus 4.10 for controls, overall empirical p-value<0.001). The significant excess relatedness was still observed when close relationships were ignored, supporting a specific genetic contribution rather than only a family environmental effect. This study supports a specific genetic contribution in the risk for the low BMI phenotype. Better understanding of the genetic contribution to low BMI holds promise for weight regulation and potentially for novel strategies in the treatment of leanness and obesity.

Are patients with inflammatory eye disease treated with systemic immunosuppressive therapy at increased risk of malignancy?

The purpose of this study is to review the literature on the risk of malignancy in patients with inflammatory eye disease (IED) treated with systemic immunosuppressive (IS) therapy. Relevant databases in transplant medicine, autoimmune diseases and literature regarding uveitis and scleritis were reviewed. Literature with regards systemic IS therapy in transplant recipients and patients with autoimmune diseases revealed a significant increase in malignancies, especially non-melanocytic skin cancers and lymphomas. Studies of patients with IED were limited in number and scope, with no studies adequately evaluating the incidence of malignancy in these patients. Difficulties associated with the evaluation of the risk of malignancy associated with IS therapy in patients with IED include the heterogeneity of the disease and treatment regimens as well as the low frequency of IED, its variable severity and the lack of adequate long-term follow-up studies. Systemic IS therapy is an important therapeutic option in the treatment of patients with severe IED. A well-designed, comprehensive, multi-centre long-term follow-up study is required to evaluate the risk of malignancy in patients with specific IED diseases treated with defined systemic IS therapy. Until such evidence is available, we recommend the adoption of preventative strategies to help minimise the risk of malignancy in such patients.

Executive function in eating disorders: the role of state anxiety.

OBJECTIVE: We examined the influence of depression and anxiety on executive function in individuals with a DSM-IV diagnosis of anorexia nervosa-restricting type, anorexia nervosa-binge-eating/purging type, bulimia nervosa, or eating disorder not otherwise specified. METHOD: We assessed 106 women after their inpatient treatment in an eating disorders program. All participants were nutritionally stable at the time of testing. RESULTS: Thirty percent of the total sample showed impaired performance on one or more tests of executive function. No differences in executive function were observed among diagnostic groups. Anxiety scores accounted for significant variance in performance for all groups. DISCUSSION: Executive function deficits were found in a minority of our sample, with significant variance in performance accounted for by self-reported anxiety. State anxiety appears to contribute to diminished executive function in women with eating disorders.

Minocycline and aspirin in the treatment of bipolar depression: a protocol for a proof-of-concept, randomised, double-blind, placebo-controlled, 2x2 clinical trial.

INTRODUCTION: New medication classes are needed to improve treatment effectiveness in the depressed phase of bipolar disorder (BD). Extant evidence suggests that BD is characterised by neural changes such as dendritic remodelling and glial and neuronal cell loss. These changes have been hypothesised to result from chronic inflammation. The principal aims of the proposed research is to evaluate the antidepressant efficacy in bipolar depression of minocycline, a drug with neuroprotective and immune-modulating properties, and of aspirin, at doses expected to selectively inhibit cyclooxygenase 1 (COX-1). METHODS AND ANALYSIS: 120 outpatients between 18 and 55 years of age, who meet DSM-IV-TR criteria for BD (type I or II) and for a current major depressive episode will be recruited to take part in a randomised, double-blind, placebo-controlled, parallel-group, proof-of-concept clinical trial following a 2×2 design. As adjuncts to existing treatment, subjects will be randomised to receive one of the four treatment combinations: placebo-minocycline plus placebo-aspirin, active-minocycline plus placebo-aspirin, placebo-minocycline plus active-aspirin or active-minocycline plus active-aspirin. The dose of minocycline and aspirin is 100 mg twice daily and 81 mg twice daily, respectively. Antidepressant response will be evaluated by assessing changes in the Montgomery-Asberg Depression Rating Scale scores between baseline and the end of the 6-week trial. As secondary outcome measures, the anti-inflammatory effects of minocycline and aspirin will be tested by measuring pre-treatment and post-treatment levels of C reactive protein and inflammatory cytokines. ETHICS AND DISSEMINATION: Minocycline has been widely used as an antibiotic in doses up to 400 mg/day. Low-dose aspirin has been safely used on a worldwide scale for its role as an antithrombotic and thrombolytic. The study progress will be overseen by a Data, Safety and Monitoring Board, which will meet once every 6 months. Results of the study will be published in peer-reviewed publications. TRIAL REGISTRATION NUMBER: Clinical Trials.gov: NCT01429272.