Reticulated phototoxic eruption in a patient on long-term diltiazem therapy

Diltiazem hydrochloride is a commonly prescribed medication in the treatment of cardiovascular disease. A case of diltiazem-induced hyperpigmentation in a patient after significant sun exposure is reported. The morphological appearance was reticulated and slate-gray to blue in color. The pathogenesis of the hyperpigmentation is discussed and possible treatment options are reviewed.     

Differential regional effects of methamphetamine on dopamine transport

Multiple high-dose methamphetamine administrations cause long-lasting (>1 week) deficits in striatal dopaminergic neuronal function. This stimulant likewise causes rapid (within 1 h) and persistent (at least 48 h) decreases in activities of striatal: 1) dopamine transporters, as assessed in synaptosomes; and 2) vesicular monoamine transporter -2 (VMAT-2), as assessed in a non-membrane-associated (referred to herein as cytoplasmic) vesicular subcellular fraction. Importantly, not all brain areas are vulnerable to methamphetamine-induced long-lasting deficits. Similarly, the present study indicates that methamphetamine exerts differential acute effects on monoaminergic transporters according to brain region. In particular, results revealed that in the nucleus accumbens, methamphetamine rapidly, but reversibly (within 24 h), decreased plasmalemmal dopamine transporter function, without effect on plasmalemmal dopamine transporter immunoreactivity. Methamphetamine also rapidly and reversibly (within 48 h) decreased cytoplasmic VMAT-2 function in this region, with relatively little effect on cytoplasmic VMAT-2 immunoreactivity. In contrast, methamphetamine did not alter either dopamine transporter or VMAT-2 activity in the hypothalamus. Noteworthy, the nucleus accumbens and hypothalamus did not display the persistent long-lasting striatal dopamine depletions caused by the stimulant. Taken together, these data suggest that deficits in plasmalemmal and vesicular monoamine transporter activity lasting greater than 24-48 h may be linked to the long-lasting dopaminergic deficits caused by methamphetamine and appear to be region specific.     

Induced Microphase Separation in Hybrid Composite Polymer Electrolytes Based on Poly(acrylonitrile‐r‐butadienes) and Ionic Liquids

Novel hybrid, composite polymer electrolytes (HCPEs) based on poly(acrylonitrile‐r‐butadiene) (PAN‐r‐PB), CN‐modified silica nanoparticles (CN‐MSNs), Li triflate, and ionic liquids (ILs) are synthesized. Using a combination of methods, it is demonstrated that these materials segregate into PAN‐rich and PB‐rich phases, the behavior of which changes depending on the IL type. The incorporation of ILs containing hexyl and octyl substituents at the imidazolium rings leads to a higher mobility of the PB‐rich phase and a decrease of the density of the neighboring PAN‐rich phase, allowing an improvement of the Li ion conductivity. However, with an increase of the substituent length from decyl to dodecyl, ordering of the hydrophobic tails in the PB‐rich phase leads to both stiffening of the latter and corresponding ordering of the ionic pairs of ILs, resulting in a decreased conductivity. The results of this work are broadly applicable for controlling the structure and properties of polymeric materials exhibiting microphase segregation.

     

Change in Work–Time Control and Work–Home Interference Among Swedish Working Men and Women: Findings from the SLOSH Cohort Study

Purpose

The aim is to study the influence of change in work–time control (WTC) on work–home interference (WHI) while adjusting for other work-related factors, demographics, changes at work and WHI at baseline among women and men. An additional aim was to explore sex differences in the relation between change in WTC and WHI.

Methods

The study included working participants of the Swedish Longitudinal Occupational Survey of Health (SLOSH) study of the third (2010) and fourth (2012) waves (n?=?5440). Based on a seven-item index, four groups of WTC were formed: stable high (40 %), stable low (42 %), increasing (9 %), or decreasing (9 %) WTC over the 2 years. WHI was measured by four items and individuals were categorised in whether suffering or not suffering of WHI. Sex-stratified logistic regression analyses with 95 % confidence intervals (CI) were used to estimate the odds of experiencing WHI by change in WTC.

Results

Controlling for demographics and work-related factors, women with stable low (OR?=?1.46; 95 % CI 1.14–1.88) and women and men with decreasing WTC (women OR?=?1.99; 95 % CI 1.38–2.85; men OR?=?1.80; 95 % CI 1.18–2.73) had higher odds of WHI than those with a stable high WTC. Additionally, adjusting for changes at work and WHI at baseline did not alter the results substantially. Interaction analysis did not reveal any significant sex difference in the relation between WTC and WHI.

Conclusions

For both women and men decreased and for women only, low control over working hours resulted in WHI also after adjusting for work-related factors and demographics.

     

The genetics,structure and function of the M1 aminopeptidase oxytocinase subfamily and their therapeutic potential in immune-mediated disease

The oxytocinase subfamily of M1 aminopeptidases plays an important role in processing and trimming of peptides for presentation on major histocompatibility (MHC) Class I molecules. Several large-scale genomic studies have identified association of members of this family of enzymes, most notably ERAP1 and ERAP2, with immune-mediated diseases including ankylosing spondylitis, psoriasis and birdshot chorioretinopathy. Much is now known about the genetics of these enzymes and how genetic variants alter their function, but how these variants contribute to disease remains largely unresolved. Here we discuss what is known about their structure and function and highlight some of the knowledge gaps that affect development of drugs targeting these enzymes.     

Orthodontic management of the patientundergoing mandibular distraction osteogenesis

Distraction osteogenesis is a gradual incremental bone-lengthening technique that requires very precise treatment planning and surgical execution. Subtle variation in the position of the corticotomy/osteotomy or in the position of the distraction device will affect the ultimate position of the tooth-bearing (distal) segment. Other functional and/or anatomic factors (that at this time are not well understood) also have an influence on the direction in which the tooth-bearing segment moves during distraction. These factors combine to create a discrepancy between the planned direction and the actual or observed direction of distraction. The charge for the orthodontist is to plan, as carefully as possible and in concert with the surgeon, the direction (vector) in which the tooth-bearing segment will travel during distraction. Further, the orthodontist must be able to modify the position that the tooth-bearing segment takes by exerting orthopedic and orthodontic forces and by making adjustments to the distraction device. In addition, the orthodontist must prepare the dentition before distraction, manage the dentition during distraction, and finish the occlusion after distraction in a manner that is different from more traditional jaw-respositioning techniques.     

Postexposure immunoprophylaxis of primary isolates by an antibody to HIV receptor complex

mAb B4 is a monoclonal antibody directed against HIV receptor complex. The antibody had broad neutralizing activity against HIV and provided postexposure prophylaxis to hu-peripheral blood leukocyte (PBL)-severe combined immunodeficient mice and chimpanzees. B4 recognized a complex receptor site for HIV on the T cell surface that includes CD4 and also may be influenced by interaction with HIV coreceptors. mAb B4 preferentially neutralized primary HIV-1 isolates compared with T cell line-adapted strains, including syncytium-inducing and non-syncytium-inducing phenotypes, representatives from HIV-1 subtypes A-G, as well as HIV-2, simian immunodeficiency virus, and chimeric simian/human immunodeficiency virus (SHIV). Neutralization was demonstrated in both pre- and postinfection models. The administration of mAb B4 after infectious challenge totally interrupted the infection of hu-PBL-severe combined immunodeficient mice by PBL-grown HIV-1 and the infection of chimpanzees by chimp-adapted HIV-1. This mode of protection suggested that the anti-HIV receptor antibody is efficacious for prophylaxis after exposure to HIV and for prevention of maternal transmission and may be an effective antiretroviral agent for treatment.     

Classification of otitis media and surgical principles.

Otitis media is an important disease of children and adults and is caused by multiple interrelated factors, including infection, eustachian tube dysfunction, allergy, and barotrauma. This article includes a pertinent review of the literature regarding otitis media. The pathogenesis, classification, and treatment of otitis media in children and adults are also reviewed in this article. Additionally, therapy is discussed with emphasis on the surgical options appropriate at each stage.     

Optimizing clinical phenotyping to better delineate the complex relationship between type 2 diabetes and Alzheimer’s disease

Alzheimer’s disease (AD) is the most common form of dementia, and its prevalence is increasing rapidly. According to the Alzheimer’s Association, over 5 million adults in the United States over the age of 65 years currently have AD, and this number is expected to exceed 13 million by 2050 in the absence of novel, preventative strategies. Epidemiologic studies have implicated the presence of type 2 diabetes mellitus (T2DM) specifically at midlife as a key modifiable risk factor for AD, and AD may increase risk of dysglycemia and T2DM. However, data have been inconsistent with regard to the magnitude of AD risk attributable to T2DM, and the pathways underlying this apparent relationship remain poorly understood. Elucidating the impact of T2DM on AD risk and progression requires greater attention to the myriad facets of T2DM pathophysiology, its comorbid conditions, and attendant treatment modalities, all of which may differentially impact the relationships among T2DM, cognitive decline, and AD. This mini‐review will summarize the discrete facets of T2DM that may influence AD risk and highlight the importance of careful clinical phenotyping in both epidemiologic and interventional studies to better delineate the key pathways and mechanisms linking T2DM and AD.