Ophthalmoplegia and Slurred Speech in an Intravenous Drug User

A 35-year-old heroin user presented with acute, progressive diplopia and slurred speech. Krishna and colleagues discuss the diagnosis and management of this patient

Physicians’ Preferences for Bone Metastases Drug Therapy in the United States

AbstractObjectiveSeveral characteristics of bone-targeted agents are considered when making treatment decisions. This study evaluated physicians’ therapy preferences for preventing skeletal-related events (SREs) in patients with bone metastases secondary to solid tumors.MethodsA Web-enabled, discrete-choice experiment online survey was conducted among physicians who treated patients with bone metastases and solid tumors in the United States. Respondents chose between pairs of hypothetical medications defined by combinations of six attributes at varying levels for two hypothetical patients. Preference weights for attribute levels were estimated using a random-parameters logit model.ResultsIn total, 200 physicians completed the survey. Their mean age was 52 years, 57% were in practice for more than 15 years, 37% were oncologists, and 65% treated 10 or fewer patients with bone metastases weekly. Out-of-pocket cost to patients was the most important attribute overall. Among clinical outcomes, time to first SRE and risk of renal impairment were the most important attributes. Statistically significant preferences were observed for all attribute levels for time to first SRE, risk of renal impairment, and mode of administration. Predicted choice probability analysis showed that physicians preferred a hypothetical medication with attributes similar to those of denosumab over one with attributes similar to those of zoledronic acid.ConclusionsPhysicians indicated that clinical attributes are important when considering bone-targeting therapy for bone metastases, but consistent with the current health care landscape, patient out-of-pocket cost was the most important. With health care costs being increasingly shifted to patients, physicians require accurate information about co-pays and assistance programs to avoid patients receiving less costly, yet potentially inferior, treatment

ECAL Front-End Monitoring in the CMS experiment

The CMS detector at LHC is equipped with a high precision lead tungstate crystal electromagnetic calorimeter (ECAL). The front-end boards and the photodetectors are monitored using a network of DCU (Detector Control Unit) chips located on the detector electronics. The DCU data are accessible through token rings controlled by an XDAQ based software component. Relevant parameters are transferred to DCS (Detector Control System) and stored into the Condition DataBase. The operational experience from the ECAL commissioning at the CMS experimental cavern is discussed and summarized

Photochemistry of ketones adsorbed on size/shape selective zeolites. A supramolecular approach to persistent carbon centered radicals

2H NMR, EPR, computational and product analyses of the photolysis of 2,4-diphenylpentan-3-one (DPP) adsorbed on MFI size/shape selective zeolites are consistent with supramolecular structural changes as a function of surface coverage that provide a novel method for the generation of persistent diffusing organic free radicals

A systematic review to explore the effectiveness of physical health and psychosocial interventions on anxiety, depression and quality of life in people living with blood cancer

Problem identification. Anxiety and depression are more prevalent in hematological cancer patients who experience unpredictable illness trajectories and aggressive treatments compared to solid tumor patients. Efficacy of psychosocial interventions targeted at blood cancer patients is relatively unknown. This systematic review examined trials of physical health and psychosocial interventions intending to improve levels of anxiety, depression, and/or quality of life in adults with hematological cancers. Literature search. PubMed and CINAHL databases were used to perform a systematic review of literature using PRISMA guidelines. Data evaluation/synthesis. Twenty-nine randomized controlled trials of 3232 participants were included. Thirteen studies were physical therapy, nine psychological, five complementary, one nutritional and one spiritual therapy interventions. Improvements were found in all therapy types except nutritional therapy. Conclusions. Interventions that included personal contact with clinicians were more likely to be effective in improving mental health than those without. Implications for psychosocial oncology. Various psychosocial interventions can be offered but interactive components appear crucial for generating long-standing improvements in quality of life, anxiety and depression

Sorting nexin-27 regulates AMPA receptor trafficking through the synaptic adhesion protein LRFN2

The endosome-associated cargo adaptor sorting nexin-27 (SNX27) is linked to various neuropathologies through sorting of integral proteins to the synaptic surface, most notably AMPA receptors. To provide a broader view of SNX27-associated pathologies, we performed proteomics in rat primary neurons to identify SNX27-dependent cargoes, and identified proteins linked to excitotoxicity, epilepsy, intellectual disabilities, and working memory deficits. Focusing on the synaptic adhesion molecule LRFN2, we established that SNX27 binds to LRFN2 and regulates its endosomal sorting. Furthermore, LRFN2 associates with AMPA receptors and knockdown of LRFN2 results in decreased surface AMPA receptor expression, reduced synaptic activity, and attenuated hippocampal long-term potentiation. Overall, our study provides an additional mechanism by which SNX27 can control AMPA receptor-mediated synaptic transmission and plasticity indirectly through the sorting of LRFN2 and offers molecular insight into the perturbed function of SNX27 and LRFN2 in a range of neurological conditions

A case of polyarteritis nodosa limited to the right calf muscles, fascia, and skin: a case report

<p>Abstract</p> <p>Introduction</p> <p>Limited polyarteritis nodosa is a rare benign disease that usually responds well to systemic corticosteroid treatment. We report a case limited to calf muscles, fascia, and skin treated with local corticosteroid therapy directed to the affected areas by ultrasound guidance.</p> <p>Case presentation</p> <p>A 36-year-old Caucasian woman presented with a 10-month history of progressive right calf pain and swelling, which were unresponsive to treatment with non-steroidal anti-inflammatory drugs and physiotherapy. An examination revealed a swollen tender right calf with indurated overlying skin. Laboratory investigations showed an erythrocyte sedimentation rate of 24 mm/hour and a C-reactive protein of 15 mg/dl. Full blood count, renal profile, and creatinine kinase level were normal. A full autoantibody screen and hepatitis B and C serology results were negative. A chest X-ray was unremarkable. Magnetic resonance imaging of the right leg revealed increased signal intensity in T2-weighted images and this was suggestive of extensive inflammatory changes of the gastrocnemius muscle and, to a lesser extent, the soleus muscle. There were marked inflammatory changes throughout the gastrocnemius muscle and the subcutaneous tissue circumferentially around the right lower leg. A biopsy of affected skin, muscle, and fascia showed histopathological features consistent with polyarteritis nodosa, including small-vessel vasculitis with fibrinoid changes in the vessel wall and intense perivascular and focal mural chronic inflammatory changes. Our patient declined treatment with oral steroids. She received a course of ultrasound-guided injections of steroid (Depo-Medrone, methylprednisolone) in the involved muscle area and commenced maintenance azathioprine with a good response.</p> <p>Conclusions</p> <p>Limited polyarteritis nodosa is rare and affects middle-aged individuals. In most cases, treatment with moderate- to high-dose corticosteroids gives symptomatic relief within one week. Resistant cases require treatment with cytotoxics or intravenous immunoglobulins. This case demonstrates response to local targeted steroid therapy as an alternative to systemic steroids.</p

MicroRNA inhibition using antimiRs in acute human brain tissue sections

Antisense inhibition of microRNAs is an emerging preclinical approach to pharmacoresistant epilepsy. A leading candidate is an "antimiR" targeting microRNA-134 (ant-134), but testing to date has used rodent models. Here, we develop an antimiR testing platform in human brain tissue sections. Brain specimens were obtained from patients undergoing resective surgery to treat pharmacoresistant epilepsy. Neocortical specimens were submerged in modified artificial cerebrospinal fluid (ACSF) and dissected for clinical neuropathological examination, and unused material was transferred for sectioning. Individual sections were incubated in oxygenated ACSF, containing either ant-134 or a nontargeting control antimiR, for 24 h at room temperature. RNA integrity was assessed using BioAnalyzer processing, and individual miRNA levels were measured using quantitative reverse transcriptase polymerase chain reaction. Specimens transported in ACSF could be used for neuropathological diagnosis and had good RNA integrity. Ant-134 mediated a dose-dependent knockdown of miR-134, with approximately 75% reduction of miR-134 at 1 μmol L-1 and 90% reduction at 3 μmol L-1 . These doses did not have off-target effects on expression of a selection of three other miRNAs. This is the first demonstration of ant-134 effects in live human brain tissues. The findings lend further support to the preclinical development of a therapy that targets miR-134 and offer a flexible platform for the preclinical testing of antimiRs, and other antisense oligonucleotide therapeutics, in human brain

Exercise and other nonpharmacological strategies to reduce blood pressure in older adults: a systematic review and meta-analysis

The incidence of hypertension increases with advancing age and represents a significant burden of disease. Lifestyle modification represents the first-line intervention in treatment algorithms; however, the majority of evidence for this comes from studies involving young participants using interventions that may not always be feasible in the elderly. This manuscript presents a systematic review of all randomized controlled trials involving participants with a mean age of 65 or over investigating nonpharmacological strategies to reduce blood pressure (BP). Fifty-three randomized controlled trials were included. The majority of interventions described aerobic exercise training, dynamic resistance exercise training, or combined aerobic and dynamic resistance exercise training (COM), with limited studies reporting isometric exercise training or alternative lifestyle strategies. Aerobic exercise training, dynamic resistance exercise training, COM, and isometric exercise training all elicited significant reductions in both systolic and diastolic BP, with no additional benefit of COM compared with single modality exercise training. Three months of traditional exercise-based lifestyle intervention may produce a reduction in BP of approximately 5 mmHg systolic and 3 mmHg diastolic in older individuals, similar to that expected in younger individuals