Ceftaroline in complicated skin and skin-structure infections

Ceftaroline is an advanced-generation cephalosporin antibiotic recently approved by the US Food and Drug Administration for the treatment of complicated skin and skin-structure infections (cSSSIs). This intravenous broad-spectrum antibiotic exerts potent bactericidal activity by inhibiting bacterial cell wall synthesis. A high affinity for the penicillin-binding protein 2a (PBP2a) of methicillin-resistant Staphylococcus aureus (MRSA) makes the drug especially beneficial to patients with MRSA cSSSIs. Ceftaroline has proved in multiple well-conducted clinical trials to have an excellent safety and efficacy profile. In adjusted doses it is also recommended for patients with renal or hepatic impairment. Furthermore, the clinical effectiveness and high cure rate demonstrated by ceftaroline in cSSSIs, including those caused by MRSA and other multidrug-resistant strains, warrants its consideration as a first-line treatment option for cSSSIs. This article reviews ceftaroline and its pharmacology, efficacy, and safety data to further elucidate its role in the treatment of cSSSIs

Bitten to the Bone: A Case of Anxiety-Induced Osteomyelitis

Onychophagia is a habitual nail-biting disorder, usually associated with mental or emotional diseases. It affects 20-30% of the population in all age groups. Human bites have the potential to become serious injuries due to high virulence in the human oral flora and may often require hospital admission, antibiotics and even debridement in the operating room. Thus, repetitive nail biting has the potential to be limb-threatening if not treated early and appropriately. We present a 49-year-old Spanish-speaking gentleman, with a past medical history of repetitive nail biting secondary to severe anxiety, major depression disorder, bilateral hand neuropathy secondary to diabetes mellitus (DM) type 2 who was initially admitted to the hospital due to cellulitis of the fingers with suspected osteomyelitis in the right hand. Anxiety was being treated by psychiatrist with paroxetine however, given no improvement and prolonged follow-ups, the primary care physician (PCP) added hydroxyzine and scheduled alprazolam in an attempt to minimize symptoms. Despite these efforts, patient continued with nail biting. On initial physical exam, the patient had a lack of fingernails and multiple wounds at various stages of healing across all digits. The distal and middle phalanges of the third right digit showed increased erythema and swelling and band tightening. Patient was started on broad-spectrum antibiotics. Initial radiography of the right hand was concerning for osteomyelitis which was later confirmed with Magnetic Resonance Imaging (MRI). Infectious disease specialist agreed on a course of cefepime, vancomycin and metronidazole. On admission, hand surgeon did not see a need for amputation and patient was treated conservatively. Due to minimal improvement after six days on IV antibiotics, patient underwent fasciotomy of the flexor compartment of the right middle finger after patient rejected hand surgeon\u27s recommendation for amputation. He was discharged to a skilled nursing facility where he was to continue intravenous antibiotics for an additional four weeks. The vulnerable patient population of South Texas is predominately Hispanic, Spanish-speaking and uninsured. It is imperative to treat psychiatric disorders early to prevent complications, however, given the low numbers of psychiatrists in the Rio Grande Valley and even fewer who speak Spanish it is not unusual to find an appointment in more than six months. In this case, we observe how a trivial everyday behavior can lead to limb-threatening complications if not treated early and appropriately

IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome

Expansion of the polyglutamine repeat within the protein Huntingtin (Htt) causes Huntington's disease, a neurodegenerative disease associated with aging and the accumulation of mutant Htt in diseased neurons. Understanding the mechanisms that influence Htt cellular degradation may target treatments designed to activate mutant Htt clearance pathways. We find that Htt is phosphorylated by the inflammatory kinase IKK, enhancing its normal clearance by the proteasome and lysosome. Phosphorylation of Htt regulates additional post-translational modifications, including Htt ubiquitination, SUMOylation, and acetylation, and increases Htt nuclear localization, cleavage, and clearance mediated by lysosomal-associated membrane protein 2A and Hsc70. We propose that IKK activates mutant Htt clearance until an age-related loss of proteasome/lysosome function promotes accumulation of toxic post-translationally modified mutant Htt. Thus, IKK activation may modulate mutant Htt neurotoxicity depending on the cell's ability to degrade the modified species

3D characterization of CdSe nanoparticles attached to carbon nanotubes

The crystallographic structure of CdSe nanoparticles attached to carbon nanotubes has been elucidated by means of high resolution transmission electron microscopy and high angle annular dark field scanning transmission electron microscopy tomography. CdSe rod-like nanoparticles, grown in solution together with carbon nanotubes, undergo a morphological transformation and become attached to the carbon surface. Electron tomography reveals that the nanoparticles are hexagonal-based with the (001) planes epitaxially matched to the outer graphene layer.Comment: 7 pages, 8 figure

ACR guidance document on MR safe practices: 2013

Because there are many potential risks in the MR environment and reports of adverse incidents involving patients, equipment and personnel, the need for a guidance document on MR safe practices emerged. Initially published in 2002, the ACR MR Safe Practices Guidelines established de facto industry standards for safe and responsible practices in clinical and research MR environments. As the MR industry changes the document is reviewed, modified and updated. The most recent version will reflect these changes. J. Magn. Reson. Imaging 2013;37:501–530. © 2013 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96674/1/24011_ftp.pd

Managing a mega-project to explore and enhance careers: insights from Global Entrepreneurial Talent Management 3

Contemporary careers are changing and face many challenges. This creates a need for innovative cross-cultural and multidisciplinary research. In this chapter, twenty-three participants in a European/South Korean research mega-project provide an overview of their diverse experiences of trans-national, trans-sectoral, and trans-generational work. First, the project’s architects explore the context and rationale in five countries, selection of partners, securing funding and the underpinning principles of ‘strategic entrepreneurship’ and ‘multi-sociation’. Key workstream leaders then outline the project content, including diplomacy in research design, reflecting gender, ensuring impact, capturing learning, communicating to various audiences. Major aspects of Implementation are described: quality management, managing academics and risk, transnational and trans-sectorial working (between academia and industry), novel methodologies and finally the career implications for PhD students involved. These are honest and pragmatic reflections on the way to best practice

APOE E4 is associated with impaired self-declared cognition but not disease risk or age of onset in Nigerians with Parkinson's disease

The relationship between APOE polymorphisms and Parkinson's disease (PD) in black Africans has not been previously investigated. We evaluated the association between APOE polymorphic variability and self-declared cognition in 1100 Nigerians with PD and 1097 age-matched healthy controls. Cognition in PD was assessed using the single item cognition question (item 1.1) of the MDS-UPDRS. APOE genotype and allele frequencies did not differ between PD and controls (p > 0.05). No allelic or genotypic association was observed between APOE and age at onset of PD. In PD, APOE ε4/ε4 conferred a two-fold risk of cognitive impairment compared to one or no ε4 (HR: 2.09 (95% CI: 1.13-3.89; p = 0.02)), while APOE ε2 was associated with modest protection against cognitive impairment (HR: 0.41 (95% CI 0.19-0.99, p = 0.02)). Of 773 PD with motor phenotype and APOE characterized, tremor-dominant (TD) phenotype predominated significantly in ε2 carriers (87/135, 64.4%) compared to 22.2% in persons with postural instability/gait difficulty (PIGD) (30/135) and 13.3% in indeterminate (ID) (18/135, 13.3%) (p = 0.037). Although the frequency of the TD phenotype was highest in homozygous ε2 carriers (85.7%), the distribution of motor phenotypes across the six genotypes did not differ significantly (p = 0.18). Altogether, our findings support previous studies in other ethnicities, implying a role for APOE ε4 and ε2 as risk and protective factors, respectively, for cognitive impairment in PD