Cancer risk in persons with HIV/AIDS in India: a review and future directions for research

Background India has a large and evolving HIV epidemic. Little is known about cancer risk in Indian persons with HIV/AIDS (PHA) but risk is thought to be low. Methods To describe the state of knowledge about cancer patterns in Indian PHA, we reviewed reports from the international and Indian literature. Results As elsewhere, non-Hodgkin lymphomas dominate the profile of recognized cancers, with immunoblastic/large cell diffuse lymphoma being the most common type. Hodgkin lymphoma is proportionally increased, perhaps because survival with AIDS is truncated by fatal infections. In contrast, Kaposi sarcoma is rare, in association with an apparently low prevalence of Kaposi sarcoma-associated herpesvirus. If confirmed, the reasons for the low prevalence need to be understood. Cervical, anal, vulva/vaginal and penile cancers all appear to be increased in PHA, based on limited data. The association may be confounded by sexual behaviors that transmit both HIV and human papillomavirus. Head and neck tumor incidence may also be increased, an important concern since these tumors are among the most common in India. Based on limited evidence, the increase is at buccal/palatal sites, which are associated with tobacco and betel nut chewing rather than human papillomavirus. Conclusion With improving care of HIV and better management of infections, especially tuberculosis, the longer survival of PHA in India will likely increase the importance of cancer as a clinical problem in India. With the population's geographic and social diversity, India presents unique research opportunities that can be embedded in programs targeting HIV/AIDS and other public health priorities

Inhibitory effect of 4-O-methylhonokiol on lipopolysaccharide-induced neuroinflammation, amyloidogenesis and memory impairment via inhibition of nuclear factor-kappaB in vitro and in vivo models

<p>Abstract</p> <p>Background</p> <p>Neuroinflammation is important in the pathogenesis and progression of Alzheimer disease (AD). Previously, we demonstrated that lipopolysaccharide (LPS)-induced neuroinflammation caused memory impairments. In the present study, we investigated the possible preventive effects of 4-<it>O</it>-methylhonokiol, a constituent of <it>Magnolia officinalis</it>, on memory deficiency caused by LPS, along with the underlying mechanisms.</p> <p>Methods</p> <p>We investigated whether 4-<it>O</it>-methylhonokiol (0.5 and 1 mg/kg in 0.05% ethanol) prevents memory dysfunction and amyloidogenesis on AD model mice by intraperitoneal LPS (250 μg/kg daily 7 times) injection. In addition, LPS-treated cultured astrocytes and microglial BV-2 cells were investigated for anti-neuroinflammatory and anti-amyloidogenic effect of 4-<it>O</it>-methylhonkiol (0.5, 1 and 2 μM).</p> <p>Results</p> <p>Oral administration of 4-<it>O</it>-methylhonokiol ameliorated LPS-induced memory impairment in a dose-dependent manner. In addition, 4-<it>O</it>-methylhonokiol prevented the LPS-induced expression of inflammatory proteins; inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as activation of astrocytes (expression of glial fibrillary acidic protein; GFAP) in the brain. In <it>in vitro </it>study, we also found that 4-<it>O</it>-methylhonokiol suppressed the expression of iNOS and COX-2 as well as the production of reactive oxygen species, nitric oxide, prostaglandin E₂, tumor necrosis factor-α, and interleukin-1β in the LPS-stimulated cultured astrocytes. 4-<it>O</it>-methylhonokiol also inhibited transcriptional and DNA binding activity of NF-κB via inhibition of IκB degradation as well as p50 and p65 translocation into nucleus of the brain and cultured astrocytes. Consistent with the inhibitory effect on neuroinflammation, 4-<it>O</it>-methylhonokiol inhibited LPS-induced Aβ_1-42generation, β- and γ-secretase activities, and expression of amyloid precursor protein (APP), BACE1 and C99 as well as activation of astrocytes and neuronal cell death in the brain, in cultured astrocytes and in microglial BV-2 cells.</p> <p>Conclusion</p> <p>These results suggest that 4-<it>O</it>-methylhonokiol inhibits LPS-induced amyloidogenesis via anti-inflammatory mechanisms. Thus, 4-<it>O</it>-methylhonokiol can be a useful agent against neuroinflammation-associated development or the progression of AD.</p

Giant Planet Formation and Migration

© 2018, The Author(s). Planets form in circumstellar discs around young stars. Starting with sub-micron sized dust particles, giant planet formation is all about growing 14 orders of magnitude in size. It has become increasingly clear over the past decades that during all stages of giant planet formation, the building blocks are extremely mobile and can change their semimajor axis by substantial amounts. In this chapter, we aim to give a basic overview of the physical processes thought to govern giant planet formation and migration, and to highlight possible links to water delivery.S.-J. Paardekooper is supported by a Royal Society University Research Fellowship. A. Johansen is supported by the Knut and Alice Wallenberg Foundation, the Swedish Research Council (grant 2014-5775) and the European Research Council (ERC Starting Grant 278675-PEBBLE2PLANET)

Development and Validation of Prediction Models for Severe Complications After Acute Ischemic Stroke: A Study Based on the Stroke Registry of Northwestern Germany

Background The treatment of stroke has been undergoing rapid changes. As treatment options progress, prediction of those under risk for complications becomes more important. Available models have, however, frequently been built based on data no longer representative of today's care, in particular with respect to acute stroke management. Our aim was to build and validate prediction models for 4 clinically important, severe outcomes after stroke. Methods and Results We used German registry data from 152 710 patients with acute ischemic stroke obtained in 2016 (development) and 2017 (validation). We took into account potential predictors that were available at admission and focused on in-hospital mortality, intracranial mass effect, secondary intracerebral hemorrhage, and deep vein thrombosis as outcomes. Validation cohort prediction and calibration performances were assessed using the following 4 statistical approaches: logistic regression with backward selection, l1-regularized logistic regression, k-nearest neighbor, and gradient boosting classifier. In-hospital mortality and intracranial mass effects could be predicted with high accuracy (both areas under the curve, 0.90 [95% CI, 0.90-0.90]), whereas the areas under the curve for intracerebral hemorrhage (0.80 [95% CI, 0.80-0.80]) and deep vein thrombosis (0.73 [95% CI, 0.73-0.73]) were considerably lower. Stroke severity was the overall most important predictor. Models based on gradient boosting achieved better performances than those based on logistic regression for all outcomes. However, area under the curve estimates differed by a maximum of 0.02. Conclusions We validated prediction models for 4 severe outcomes after acute ischemic stroke based on routinely collected, recent clinical data. Model performance was superior to previously proposed approaches. These predictions may help to identify patients at risk early after stroke and thus facilitate an individualized level of care

Useful Visual Outcomes after Treatment of Bacillus cereus Endophthalmitis

Purpose:Bacillus cereus endophthalmitis occurring after penetrating ocular trauma has been almost always associated with a poor visual outcome. The purpose of our study was to review and report patients who had useful visual acuity outcomes. Methods: The study group consisted of five patients from a single medical center with penetrating ocular trauma and endophthalmitis caused by B. cereus. The study population was derived from a review of the microbiology records, clinical records, and operative reports of patients with culture-proven, post-traumatic endophthalmitis over a 15-year period. Patients were only included if the final visual acuity outcomes were 20/200 or better. Results: All five patients had penetrating ocular injuries, and four patients had a retained intraocular foreign body. Endophthalmitis was diagnosed preoperatively in three patients and intraoperatively in two patients. All patients underwent pars plana vitrectomy and injection of intravitreal and periocular antibiotics. Postoperatively, a rhegmatogenous retinal detachment developed in three patients between 4 weeks and 12 months after the injury (average, 19 weeks); all retinal detachments were reattached with additional vitreoretinal surgery. Final postoperative visual acuities were 20/200 (two patients), 20/30 (one patient), and 20/25 (two patients). The postoperative follow-up time interval ranged from 12 months to 30 months (average, 19.2 months). Conclusion: The current series adds further support to the observation that certain eyes with post-traumatic B. cereus endophthalmitis may be associated with preservation of anatomic integrity and restoration of useful visual acuity