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Mr. Dickens is a principal at a local high school, who has been seeing you for the past 2 years about his chronic urticaria. He is typically a very pleasant and compliant patient. As an educator, Mr. Dickens values the patient education component of his visits with you, and is generally eager to share his experiences of living with a chronic skin condition. When he started with you, each urticarial episode lasted up to 12 h and occurred approximately every other day. Once aggressive therapy was instituted, his condition gradually improved to the point where he now experiences an episode every other week, with each one lasting no more than 1 h. Today is his regular 3-month follow-up, and the receptionist noted that he appeared quite unhappy.

Ms. Alvarez, a 58 year-old Hispanic woman, presented with 2 years of “infestation with bugs.” The episodes started when she stayed at her friend’s house and was reportedly exposed to dirty blankets and soiled linens. She had seen many physicians, both dermatologists and non-dermatologists. She brought in a bag full of topical medications including topical steroids, anti-fungal creams, anti-bacterial ointments, and moisturizers, none of which were of benefit. She had been treated twice with permethrine (Elimite®) by a dermatologist with only transient relief of symptoms. She described in great details the life cycle and the mating habits of these parasites. She also presented to you zip-lock bags of soiled materials containing tissue papers with brown stains suspended in cloudy water. She stated unequivocally that these specimens contain the “parasites” she has described.

Mrs. Jones is a 90-year-old Caucasian female, who was brought in to see you by her son for a 12-month history of chronic biting and stinging sensations all over her body. She had not observed any bugs to bite or sting her skin; however, the sensations she felt are those that could only be created by insects. As a result of being frequently bothered by these sensations, she repeatedly picked at her skin in places she was able to reach. She also reported retrieving several types of “materials” embedded in her skin. They often appeared as insect body parts and clear, coiled fibers, which she claimed “were shed from the bugs.” She had brought some of these objects in plastic zip-lock bags to the dermatology clinic and requested you to examine them as carefully as possible.

Ms. Daisy is a 65 year-old Caucasian new patient, who presented with a 2-year history of being infested with “parasites.” She brought with her numerous items such as impeccably prepared slides of these so-called parasite carcasses, professionally taken photographs of skin debris and other inanimate objects, and articles published in scientific journals as well as the popular press discussing parasitic infestation. She has already visited numerous dermatology practitioners and one parasitology specialist, who could not identify any ecto-parasites (i.e., those infesting visible parts of the body). Her medical history included well-controlled hypertension and chronic back pain.

Mrs. Wang is a 69 year-old Asian American woman presenting with a chief complaint of being “infested with parasites” for the past 5 months. She described crawling, stinging and biting sensations that occurred spontaneously all over her body. There were a few plastic zip-lock bags containing what she believes to the parasites and their eggs. From her expressions and demeanor, the patient appeared deeply worried about and quite preoccupied with her infestation. However, upon further questioning Mrs. Wang stated that she was not entirely convinced about the existence of live organisms in her skin. She was open to other explanations, but above all, just wanted to receive a good treatment.

Mr. Northwood is a 25 year-old Caucasian man, who presented with a chief complaint of being infested by “bugs.” He reported intense, bothersome sensations of crawling, stinging, and biting, which were felt frequently all over this body. He otherwise had a clean bill of health and denied any psychological stress or emotional issues. Upon further questioning, he admitted to regular, heavy use of cocaine for the past 2 years. After he had started experimenting with cocaine, he started to notice these symptoms, which were tolerable at the time. However, the sensations progressively worsened to the point where he could no longer resist the urge to scratch or to pick at his skin. His general practitioner could not determine the cause, and as a result, referred him to your psychodermatology clinic for help.

Ms. Ellington is 34 year-old Caucasian woman presenting with a 1-year history of excoriations on easily reachable areas of the face, neck, dorsal hands, lateral arms, and upper chest. She had been referred to the psychodermatology clinic with an initial diagnosis of “psychosis.” There were no primary skin lesions as noted on the previous physical exam in her records. During the interview, she clearly appeared both embarrassed and apologetic about picking at her skin. She showed no elaborate ideation regarding the reason for her behavior. However, after you asked, “can you tell me exactly what makes you pick your skin?” She reports an intense focal pain in her skin as the cause.

Erica is a 19-year-old college student, who presented with a severe flare of her chronic plaque-type psoriasis. She describes the lesions as being very pruritic, to the point where she needs to take anti-allergy medication at night in order to fall asleep. The patient worries that she will fail her final examinations coming up next month in English Literature and Evolutionary Biology, two rather challenging courses. Despite tireless efforts to prepare for the exams, her self-assessment tests predict that she will score in the bottom half of each respective class, which is causing her significant distress. In addition, she is the captain of the cheerleading team at her university, and her responsibilities have doubled in the past few weeks due to her co-captain dropping out of the program.

Ms. Blackburn is an 83-year-old new patient, who presents with multiple lesions over her arms and legs. She relates a history of volunteering on and off for the past that she began volunteering at a community garden 6 weeks ago, and she has recently been bitten by ants. She states that the lesions from the ant bites have become progressively worse over the past few days. Her lesions have recently demonstrated crusting and weeping of yellow discharge. The patient has come to see the dermatologist because she is concerned about infection of the lesions. She also reports she has recently become very anxious and depressed, as her husband passed away 2 months ago. On physical examination, there are multiple excoriations over the extremities. In addition, during the interview, the patient constantly scratches at her arms and legs.

Ms. Bronte is a previously healthy 35 year-old woman, who presents to you as a new patient with sudden-onset generalized plaque-type psoriasis. She also complains of intermittent achy joints and a sensation of chest tightness that typically precedes each flare of psoriasis. She has received a thorough work-up from multiple specialists, including dermatology, rheumatology, and cardiology, at a respected medical institution prior to coming to you. In spite of having previously been diagnosed with psoriasis, she claims that her condition has not been fully diagnosed, and she worries about the risk of a cardiovascular event. Reports from cardiology and rheumatology revealed no obvious causes for her symptoms. The patient is sitting in front of you, appearing very anxious and distressed about her health, and pleads that you help control her psoriasis as well diagnose her heart and joint disease. In other words, she wants you to be her primary care physician (PCP).

International audience; The broadcast of periodic messages is a key functionality in vehicular ad hoc networks. In the emerging vehicular networks, IEEE 802.11p is the standard of choice to support the PHY and MAC layer functionalities. The broadcast process in IEEE 802.11p is based on the CSMA mechanism where a device transmitting a packet senses the channel for ongoing transmissions and performs a random back-off before accessing the channel. Without RTS/CTS mechanisms, carrier sensing is expected to provide a protection region around the transmitter where no other transmitters are allowed. The point process characterizing the concurrent transmitters is expected to enforce a minimum separation between concurrent transmitters. However, at increasing densities, the CSMA behavior breaks down to an ALOHA-like transmission pattern where concurrent transmitters are distributed as a Poisson point process, indicating the lack of protection around transmitters. In this paper, we model the CSMA mechanism as a slotted system and analytically characterize the critical node/packet arrival density where the CSMA mechanism approaches an ALOHAlike behavior. Further, we use tools from stochastic geometry to establish closed-form expressions for the performance metrics of the broadcast mechanism in the ALOHA regime. Finally, using ns2 (an unslotted asynchronous simulator), we compare the theoretical results with simulations

Autoinflammation is characterized by aberrant regulation of the innate immune system and often manifests as periodic fevers and systemic inflammation involving multiple organs, including the skin. Mutations leading to abnormal behavior or activity of the interleukin 1 beta (IL-1s)-processing inflammasome complex have been found in several rare autoinflammatory syndromes, for which anticytokine therapy such as IL-1 or tumor necrosis factor-alfa inhibition may be effective. It is becoming clear that features of autoinflammation also affect common dermatoses, some of which were previously thought to be solely autoimmune in origin (eg, vitiligo, systemic lupus erythematosus). Recognizing the pathogenetic role of autoinflammation can open up new avenues for the targeted treatment of complex, inflammatory dermatoses.

Recent genome-wide association studies (GWAS) have identified multiple genetic risk factors for psoriasis, but data on their association with age of onset have been marginally explored. The goal of this study was to evaluate known risk alleles of psoriasis for association with age of psoriasis onset in three well-defined case-only cohorts totaling 1,498 psoriasis patients. We selected 39 genetic variants from psoriasis GWAS and tested these variants for association with age of psoriasis onset in a meta-analysis. We found that rs10484554 and rs12191877 near HLA-C and rs17716942 near IFIH1 were associated with age of psoriasis onset with false discovery rate < 0.05. The association between rs17716942 and age of onset was not replicated in a fourth independent cohort of 489 patients (). The imputed HLA-C*06:02 allele demonstrated a much stronger association with age of psoriasis onset than rs10484554 and rs12191877. We conclude that despite the discovery of numerous psoriasis risk alleles, HLA-C*06:02 still plays the most important role in determining the age of onset of psoriasis. Larger studies are needed to evaluate the contribution of other risk alleles, including IFIH1, to age of psoriasis onset.

Patient education is a fundamental part of caring for patients. A practice gap exists, where patients want more information, while health care providers are limited by time constraints or difficulty helping patients understand or remember. To provide patient-centered care, it is important to assess the needs and goals, health beliefs, and health literacy of each patient. This allows health care providers to individualize education for patients. The use of techniques, such as gaining attention, providing clear and memorable explanations, and assessing understanding through "teach-back," can improve patient education. Verbal education during the office visit is considered the criterion standard. However, handouts, visual aids, audiovisual media, and Internet websites are examples of teaching aids that can be used as an adjunct to verbal instruction. Part II of this 2-part series on patient-physician interaction reviews the importance and need for patient education along with specific guidelines and techniques that can be used.

The motivation for developing patient-centered communication stems from a desire to enhance the quality of patient care, fulfill professional competency requirements, reduce medical errors, and improve health outcomes and patient satisfaction. Patient-centered communication skills can optimize the physician-patient relationship without significantly prolonging office visits. We propose a series of practical and generally effective techniques for verbal and nonverbal communication. We also suggest a targeted approach for specific difficult conversations that may occur frequently in the practice of dermatology.

Psoriasis is a chronic inflammatory skin disease that is characterized by thickened red plaques covered with silvery scales. Excimer laser therapy is a cutting-edge advancement in UVB phototherapy. In contrast to traditional phototherapy, the 308 nm excimer laser only targets psoriasis plaques, while it spares uninvolved skin. It allows for treatment with a supra-erythmogenic dose of UVB irradiation. Targeted UVB therapy is a possible treatment especially for many who have failed topical treatments, systemic therapy, and traditional phototherapy. For safe and effective psoriasis treatment, a combination of therapies may be used, including a combination of laser treatment with topical medications. We present two cases demonstrating effective treatment with excimer laser in conjunction with clobetasol spray and calcitriol ointment for 12 weeks. Long-term near-clearance of psoriasis was sustained after 6 months and one-year follow up periods without further therapy.

Psoriasis is a chronic, inflammatory skin condition with negative impacts both physical and psychological. Scalp psoriasis, especially around the hairline, can cause significant impairment in quality of life due to its visibility. Options for treatment of facial psoriasis, including hairline involvement, are the use of low potency topical steroids, calcineurin inhibitors, and vitamin D analogues. Though the use of excimer laser for scalp psoriasis has been reported, there are no cases or studies specifically examining excimer laser phototherapy for the treatment of hairline psoriasis. We present a case of rapid improvement of hairline psoriasis using a regimen of 308 nm excimer laser with clobetasol spray and recommend an algorithm for the optimal treatment of scalp psoriasis utilizing currently available antipsoriatic therapies.

Transition-metal catalysis is out-grown from dry-boxes where the use of inert gas atmosphere and the exclusion of moisture have been essential. Such a restriction undoubted- ly imposes limitations in the application of these reactions in organic synthesis and in the recycling of the catalysts. This article discusses some recent advances of rhodium-catalyzed carbon-carbon bond formations under the natural conditions of air and water.

Human short-chain acyl-CoA dehydrogenase (hSCAD) catalyzes the first matrix step in the mitochondrial beta-oxidation cycle for substrates with four and six carbons. Previous studies have shown that the act of substrate/product binding induces a large enzyme potential shift in acyl-CoA dehydrogenases. The objective of this work was to examine the thermodynamic regulation of this process through direct characterization of the electrochemical properties of hSCAD using spectroelectrochemical methodology. A large amount of substrate activation was observed in the enzymatic reaction of hSCAD (+33 mV), the greatest magnitude measured in any acyl-CoA dehydrogenase to date. To examine the role of the substrate as well as the product in electron transfer by hSCAD, a catalytic base mutation (E368Q) was constructed. The E368Q mutation inactivates the reductive and oxidative pathways such that the individual effects of substrate and product binding on the redox potential can be investigated. Optimal substrate (butyryl-CoA) was seen to shift the flavin redox potential slightly more positive (+38 mV) than did optimal product (crotonyl-CoA) (+31 mV), a finding opposite of that observed in another short-chain enzyme, bacterial SCAD. These results indicate that substrate redox activation occurs in hSCAD leading to a large enzyme midpoint potential shift. Substrate binding in hSCAD appears to make a larger contribution than does product to thermodynamic modulation.

The acyl-CoA dehydrogenases (ACDs) are a family of flavoenzymes involved in the metabolism of fatty acids and branched-chain amino acids. The ACDs share a similar structure and a common dehydrogenation mechanism in which a catalytic glutamate extracts a proton from an acyl-CoA substrate. The resulting charge-transfer complex subsequently passes electrons to electron-transferring flavoprotein (ETF). We previously generated catalytic residue mutants of human short-chain acyl-CoA dehydrogenase (SCAD) and isovaleryl-CoA dehydrogenase (IVD) that were difficult to characterize by traditional methods. In the present study, we developed a novel surface plasmon resonance-based assay to measure substrate binding to these mutants. Replacement of the catalytic glutamate in either SCAD or IVD with glycine resulted in a several-fold reduction in affinity for substrate. Circular dichroism studies substantiated our earlier findings that both SCAD E368G and IVD E254G are unable to form a charge-transfer complex with substrate/product. The CD spectra of IVD E254G also indicated a perturbation of the flavin environment, a finding supported by molecular modeling that predicted a shift in the conformation of a conserved tryptophan that lies in close proximity to the flavin. Lastly, competitive inhibition studies using the ETF fluorescence reduction assay suggested that SCAD E368G and IVD E254G do not effectively compete with the wild-type enzymes for the physiological electron acceptor ETF.

Thiopurine S -methyltransferase (TPMT) catalyzes the S-methylation of thiopurine drugs. TPMT genetic polymorphisms represent a striking example of the potential clinical value of pharmacogenetics. Subjects homozygous for TPMT * 3A , the most common variant allele for low activity, an allele that encodes a protein with two changes in amino acid sequence, are at greatly increased risk for life-threatening toxicity when treated with standard doses of thiopurines. These subjects have virtually undetectable levels of TPMT protein. In this study, we tested the hypothesis that TPMT * 3A might result in protein misfolding and aggregation. We observed that TPMT * 3A forms aggresomes in cultured cells and that it aggregates in vitro , functional mechanisms not previously described in pharmacogenetics. Furthermore, there was a correlation among TPMT half-life values in rabbit reticulocyte lysate, aggresome formation in COS-1 cells, and protein aggregation in vitro for the three variant allozymes encoded by alleles that include the two TPMT * 3A single-nucleotide polymorphisms. These observations were compatible with a common structural explanation for all of these effects, a conclusion supported by size-exclusion chromatography and CD spectroscopy. The results of these experiments provide insight into a unique pharmacogenetic mechanism by which common polymorphisms affect TPMT protein function and, as a result, therapeutic response to thiopurine drugs.

The acyl-CoA dehydrogenases are a family of mitochondrial flavoproteins involved in the catabolism of fatty and amino acids. Isobutyryl-CoA dehydrogenase (IBD) is involved in the catabolism of valine and catalyzes the conversion of isobutyryl-CoA to methacrylyl-CoA. The crystal structure of IBD with and without substrate has been determined to 1.76-A resolution. The asymmetric unit contains a homotetramer with substrate/product bound in two monomers. The overall structure of IBD is similar to those of previously determined acyl-CoA dehydrogenases and consists of an NH2-terminal alpha-helical domain, a medial beta-strand domain and a C-terminal alpha-helical domain. The enzyme-bound ligand has been modeled in as the reaction product, methacrylyl-CoA. The location of Glu-376 with respect to the C-2-C-3 of the bound product and FAD confirms Glu-376 to be the catalytic base. IBD has a shorter and wider substrate-binding cavity relative to short-chain acyl-CoA dehydrogenase, permitting the optimal binding of the isobutyryl-CoA substrate. The dramatic lateral expansion of the binding cavity seen in isovaleryl-CoA dehydrogenase is not observed in IBD. The conserved tyrosine or phenylalanine that defines a side of the binding cavity in other acyl-CoA dehydrogenases is replaced by a leucine (Leu-375) in the current structure. Substrate binding changes the position of some residues lining the binding pocket as well as the position of the loop containing the catalytic glutamate and subsequent helix. Three clinical mutations have been modeled to the structure. The mutations do not affect substrate binding but instead appear to disrupt protein folding and/or stability.

Short chain acyl-CoA dehydrogenase (SCAD) is a homotetrameric flavoenzyme that catalyzes the first intramitochondrial step in the beta-oxidation of fatty acids. Two polymorphisms in the coding region of the SCAD gene, 511CT (R147W) and 625GA (G185S), have been shown to be associated with an increased level of ethylmalonic acid excretion in urine, a clinical characteristic of SCAD deficiency. To characterize the biochemical consequences of these variations, in vitro site-directed mutagenesis and prokaryotic expression were used to produce the corresponding SCAD variant proteins. Both variant proteins were unstable when produced in Escherichia coli, but could be rescued and subsequently purified by coexpressing them with the bacterial chaperonin GroEL/ES. The k(cat)/K(m) values of the green wild-type, R147W, and G185S SCAD enzymes coexpressed with GroEL/ES were 33, 30, and 10 microM(-)(1) s(-)(1), respectively. There were minimal differences in the kinetic parameters measured for the green, degreened, and wild-type enzymes coexpressed with GroEL/ES, and the R147W variant when butyryl-CoA was used as a substrate. The catalytic efficiency of the G185S variant enzyme, however, was reduced compared to that of the wild-type enzyme. The thermal and guanidine HCl stability of the purified enzymes as determined by fluorescence, far-UV CD spectroscopy, and incubation-induced rest activity showed the following order of relative stability: wild-type enzymeR147WG185S. Near-UV CD spectroscopy indicated that these impairments are caused by decreased flexibility in the tertiary conformation of the two mutant enzymes. The common SCAD polymorphisms may lead to clinically relevant alterations in enzyme function.

Patient education is a fundamental part of caring for patients. A practice gap exists, where patients want more information, while health care providers are limited by time constraints or difficulty helping patients understand or remember. To provide patient-centered care, it is important to assess the needs and goals, health beliefs, and health literacy of each patient. This allows health care providers to individualize education for patients. The use of techniques, such as gaining attention, providing clear and memorable explanations, and assessing understanding through "teach-back," can improve patient education. Verbal education during the office visit is considered the criterion standard. However, handouts, visual aids, audiovisual media, and Internet websites are examples of teaching aids that can be used as an adjunct to verbal instruction. Part II of this 2-part series on patient–physician interaction reviews the importance and need for patient education along with specific guidelines and techniques that can be used.

Background & Aims: Diabetic gastroparesis (delayed gastric emptying) is a well-recognized complication of diabetes that causes considerable morbidity and makes glucose control difficult. Interstitial cells of Cajal, which express the receptor tyrosine kinase Kit, are required for normal gastric emptying. We proposed that Kit expression is lost during diabetic gastroparesis due to increased levels of oxidative stress caused by low levels of heme oxygenase-1 (HO-1), an important cytoprotective molecule against oxidative injury. Methods: Gastric emptying was measured in nonobese diabetic mice and correlated with levels of HO-1 expression and activity. Endogenous HO-1 activity was increased by administration of hemin and inhibited by chromium mesoporphyrin. Results: In early stages of diabetes, HO-1 was up-regulated in gastric macrophages and remained up-regulated in all mice that were resistant to development of delayed gastric emptying. In contrast, HO-1 did not remain up-regulated in all the mice that developed delayed gastric emptying; expression of Kit and neuronal nitric oxide synthase decreased markedly in these mice. Loss of HO-1 up-regulation increased levels of reactive oxygen species. Induction of HO-1 by hemin decreased reactive oxygen species, rapidly restored Kit and neuronal nitric oxide synthase expression, and completely normalized gastric emptying in all mice. Inhibition of HO-1 activity in mice with normal gastric emptying caused a loss of Kit expression and development of diabetic gastroparesis. Conclusions: Induction of the HO-1 pathway prevents and reverses cellular changes that lead to development of gastrointestinal complications of diabetes. Reagents that induce this pathway might therefore be developed as therapeutics.

Cardiomyopathy is an important cause of morbidity and mortality in children. Deficiency of very-long-chain acyl-CoA dehydrogenase (VLCAD), one of several nuclear encoded mitochondrial enzymes that catalyze the initial step in the beta-oxidation of straight chain fatty acids, often presents with cardiomyopathy and/or sudden death. How VLCAD deficiency causes cardiomyopathy is unclear, but appears to be related to the accumulation of toxic long-chain acyl-carnitine species rather than a block in energy metabolism. A recent report of a 5-year-old with VLCAD deficiency note resolution of her hypertrophic cardiomyopathy while on a strict low fat diet supplemented with medium chain triglycerides and carnitine. While dietary therapy for VLCAD deficiency has been beneficial to some, many people to not respond. Intercurrent illness with diminished oral intake, exercise, or fasting all increase demand for fatty acid metabolism and can potentially trigger catastrophic events even while on dietary therapy.