Atopic Dermatitis: Managing the Itch.

Atopic dermatitis has a substantial impact on sleep, appearance, psychological well-being, and other qualities of life. The visual appearance of lichenification, cheilitis, hyperpigmentation, ichthyosis, and erythema can be socially stigmatizing, and treatment of these symptoms is challenging. In managing pruritus in patients, practitioners should assess and document pruritus through questionnaires at each routine visit. Initially, practitioners should advise patients to employ nonpharmaceutical treatments such as emollients with wet wraps, elimination of triggers, changing scratching habits, and psychological interventions. If these methods of treatment are not successful or if the disease presentation is severe, pharmacological therapies should be employed. This chapter describes the therapeutic ladder for pruritus in atopic dermatitis and discusses each treatment modality in further detail for practitioners to advise their patients.First-line topical pharmaceutical agents include topical glucocorticoids and topical calcineurin inhibitors. Second-line topical agents include coal tar, menthol, capsaicin, or doxepin. After the use of topical agents has been exhausted, primary systemic agents can be applied. These include sedating antihistamines, nonsedating antihistamines, oral glucocorticoids, or cyclosporine A. Finally, neuromodulating or immunomodulating agents can be attempted, including SSRI/SNRIs, TCAs, immunosuppressants, neural modulators, and opioid receptor modulators. Outside of pharmacological treatments, phototherapy has been shown to provide a dramatic improvement of pruritus in atopic dermatitis and can be used at any stage of treatment including as a first-line agent.

Thermal ablation in pancreatic cancer: A scoping review of clinical studies.

Background: Pancreatic cancer is a deadly cancer with a 5-year survival rate less than 10%. Only 20% of patients are eligible to receive surgery at diagnosis. Hence, new therapies are needed to improve outcomes for non-surgical candidates. Thermal ablation techniques can offer a non-invasive alternative to surgery. Aim: The aim of this review is to map the literature for the use of thermal ablative techniques: Radiofrequency ablation (RFA), High-intensity focused ultrasound (HIFU), Microwave ablation (MWA), and Laser ablation (LA) in the management of patients with PC. Methods: A search strategy was applied to PUBMED and EMBASE using keywords concerning pancreatic cancer, radiofrequency ablation, ultrasound ablation, laser ablation, and microwave ablation. The studies that fit this inclusion criteria were summarized in table format and results reviewed for interpretation. Results: 72 clinical studies were included. Most of the included studies related to RFA (n=35) and HIFU (n=27). The most common study design was retrospective (n=33). Only 3 randomized control trials (RCT) were included, all of which related to RFA. Safety outcomes were reported in 53 of the 72 studies, and survival outcomes were reported in 39. Statistically significant survival benefits were demonstrated in 11 studies. Conclusion: The evidence for the benefit of MWA and LA in PC patients is limited. RFA and HIFU are safe and feasible therapies to be used in PC patients. Further RCTs where thermal techniques are standardized and reported are necessary in the future to elucidate thermal ablation's clinical utility, and before an evidence-based decision on its routine use in PC management can be considered.

BASCULE syndrome in a child with prior asymptomatic COVID-19 infection.

BASCULE syndrome, characterized by Bier anemic spots, cyanosis, and an urticaria-like eruption, has been described as a benign vasomotor dermatosis that occurs in the setting of transient tissue hypoxia. It has been postulated that dermal ischemia triggers an exaggerated vasoconstrictive arteriolar reaction, which then causes a paradoxical urticarial rash by an unknown mechanism. In patients with COVID-19, there is evidence of angiocentric inflammation leading to vasoconstriction, endothelial damage, and thrombosis. We present a case of acute-onset BASCULE syndrome appearing after asymptomatic infection with COVID-19. BASCULE syndrome should be considered in the expanding spectrum of dermatologic manifestations associated with COVID-19.

Characterization of Vimentin-Immunoreactive Astrocytes in the Human Brain.

Astrocytes are commonly identified by their expression of the intermediate filament protein glial fibrillary acidic protein (GFAP). GFAP-immunoreactive (GFAP-IR) astrocytes exhibit regional heterogeneity in density and morphology in the mouse brain as well as morphological diversity in the human cortex. However, regional variations in astrocyte distribution and morphology remain to be assessed comprehensively. This was the overarching objective of this postmortem study, which mainly exploited the immunolabeling of vimentin (VIM), an intermediate filament protein expressed by astrocytes and endothelial cells which presents the advantage of more extensively labeling cell structures. We compared the densities of vimentin-immunoreactive (VIM-IR) and GFAP-IR astrocytes in various brain regions (prefrontal and primary visual cortex, caudate nucleus, mediodorsal thalamus) from male individuals having died suddenly in the absence of neurological or psychiatric conditions. The morphometric properties of VIM-IR in these brain regions were also assessed. We found that VIM-IR astrocytes generally express the canonical astrocytic markers Aldh1L1 and GFAP but that VIM-IR astrocytes are less abundant than GFAP-IR astrocytes in all human brain regions, particularly in the thalamus, where VIM-IR cells were nearly absent. About 20% of all VIM-IR astrocytes presented a twin cell morphology, a phenomenon rarely observed for GFAP-IR astrocytes. Furthermore VIM-IR astrocytes in the striatum were often seen to extend numerous parallel processes which seemed to give rise to large VIM-IR fiber bundles projecting over long distances. Moreover, morphometric analyses revealed that VIM-IR astrocytes were more complex than their mouse counterparts in functionally homologous brain regions, as has been previously reported for GFAP-IR astrocytes. Lastly, the density of GFAP-IR astrocytes in gray and white matter were inversely correlated with vascular density, but for VIM-IR astrocytes this was only the case in gray matter, suggesting that gliovascular interactions may especially influence the regional heterogeneity of GFAP-IR astrocytes. Taken together, these findings reveal special features displayed uniquely by human VIM-IR astrocytes and illustrate that astrocytes display important region- and marker-specific differences in the healthy human brain.

Regional sequence expansion or collapse in heterozygous genome assemblies.

High levels of heterozygosity present a unique genome assembly challenge and can adversely impact downstream analyses, yet is common in sequencing datasets obtained from non-model organisms. Here we show that by re-assembling a heterozygous dataset with variant parameters and different assembly algorithms, we are able to generate assemblies whose protein annotations are statistically enriched for specific gene ontology categories. While total assembly length was not significantly affected by assembly methodologies tested, the assemblies generated varied widely in fragmentation level and we show local assembly collapse or expansion underlying the enrichment or depletion of specific protein functional groups. We show that these statistically significant deviations in gene ontology groups can occur in seemingly high-quality assemblies, and result from difficult-to-detect local sequence expansion or contractions. Given the unpredictable interplay between assembly algorithm, parameter, and biological sequence data heterozygosity, we highlight the need for better measures of assembly quality than N50 value, including methods for assessing local expansion and collapse.

Atopic Dermatitis: Managing the Itch.

Atopic dermatitis has a substantial impact on sleep, appearance, psychological well-being, and other qualities of life. The visual appearance of lichenification, cheilitis, hyperpigmentation, ichthyosis, and erythema can be socially stigmatizing, and treatment of these symptoms is challenging. In managing pruritus in patients, practitioners should assess and document pruritus through questionnaires at each routine visit. Initially, practitioners should advise patients to employ non-pharmaceutical treatments such as emollients with wet wraps, elimination of triggers, changing scratching habits, and psychological interventions. If these methods of treatment are not successful or if the disease presentation is severe, pharmacological therapies should be employed. This chapter describes the therapeutic ladder for pruritus in atopic dermatitis and discusses each treatment modality in further detail for practitioners to advise their patients.First-line topical pharmaceutical agents include topical glucocorticoids and topical calcineurin inhibitors. Second-line topical agents include coal tar, menthol, capsaicin, or doxepin. After the use of topical agents has been exhausted, primary systemic agents can be applied. These include sedating antihistamines, non-sedating antihistamines, oral glucocorticoids, or cyclosporine A. Finally, neuromodulating or immunomodulating agents can be attempted, including SSRI/SNRIs, TCAs, immunosuppressants, neural modulators, and opioid receptor modulators. Outside of pharmacological treatments, phototherapy has been shown to provide a dramatic improvement of pruritus in atopic dermatitis and can be used at any stage of treatment including as a first-line agent.

Differential Regulation of Evoked and Spontaneous Release by Presynaptic NMDA Receptors.

Presynaptic NMDA receptors (preNMDARs) control synaptic release, but it is not well understood how. Rab3-interacting molecules (RIMs) provide scaffolding at presynaptic active zones and are involved in vesicle priming. Moreover, c-Jun N-terminal kinase (JNK) has been implicated in regulation of spontaneous release. We demonstrate that, at connected layer 5 pyramidal cell pairs of developing mouse visual cortex, Mg2+-sensitive preNMDAR signaling upregulates replenishment of the readily releasable vesicle pool during high-frequency firing. In conditional RIM1αß deletion mice, preNMDAR upregulation of vesicle replenishment was abolished, yet preNMDAR control of spontaneous release was unaffected. Conversely, JNK2 blockade prevented Mg2+-insensitive preNMDAR signaling from regulating spontaneous release, but preNMDAR control of evoked release remained intact. We thus discovered that preNMDARs signal differentially to control evoked and spontaneous release by independent and non-overlapping mechanisms. Our findings suggest that preNMDARs may sometimes signal metabotropically and support the emerging principle that evoked and spontaneous release are distinct processes. VIDEO ABSTRACT.

Eruptive milia during isotretinoin therapy.

Isotretinoin (13-cis-retinoic acid) is a synthetic vitamin A derivative that is effective in the treatment of recalcitrant, nodulocystic acne. To our knowledge, there are no reports in the medical literature of milia as a side effect of isotretinoin. We report a case of eruptive facial milia in the setting of isotretinoin treatment for acne.

Differences in mRNA populations of short and long bovine conceptuses on Day 15 of gestation.

The majority of pregnancy loss in cattle occurs between Days 8 and 16 of gestation, coincident with the initiation of conceptus elongation and the onset of maternal recognition of pregnancy. Differences in conceptus length on the same day of gestation may be related to an inherent lack of developmental competency or may simply be a consequence of asynchrony with the maternal environment. The objective of this work was to characterize differential patterns of mRNA expression between short and long bovine conceptuses recovered on Day 15 of gestation. Embryos were produced from super-ovulated Holstein donor cows, and groups of Grade-1 and Grade-3 compact morulas were transferred into recipient heifers at Day 6.5 of their cycle. Conceptuses were recovered at Day 15 of gestation, and measured to assess overall length and area. Total RNA was extracted and analyzed on individual GeneChip Bovine Genome Arrays (Affymetrix, Santa Clara, CA). Gene expression was compared between conceptuses derived from the transfer of Grade-1 versus Grade-3 embryos; no differences were identified in the profiles of Day-15 conceptuses of these different embryo grades. When gene expression was compared between conceptuses classified as either short (mean length of 4.2 ± 0.1 mm [standard error]) or long (24.7 ± 1.9 mm) upon recovery at Day 15 of gestation, a total of 348 genes were differentially expressed. Of these, 221 genes were up-regulated and 127 were down-regulated in long compared to short conceptuses. In summary, differences in gene expression were identified between conceptuses recovered on Day 15 of gestation, based on their length. These data may be used to identify genes and cellular pathways involved in enhanced conceptus elongation that could serve as markers of successful pregnancy. Mol. Reprod. Dev. 83: 424-441, 2016. © 2016 Wiley Periodicals, Inc.

TonB-dependent heme iron acquisition in the tsetse fly symbiont Sodalis glossinidius.

Sodalis glossinidius is an intra- and extracellular symbiont of the tsetse fly (Glossina sp.), which feeds exclusively on vertebrate blood. S. glossinidius resides in a wide variety of tsetse tissues and may encounter environments that differ dramatically in iron content. The Sodalis chromosome encodes a putative TonB-dependent outer membrane heme transporter (HemR) and a putative periplasmic/inner membrane ABC heme permease system (HemTUV). Because these gene products mediate iron acquisition processes by other enteric bacteria, we characterized their regulation and physiological role in the Sodalis/tsetse system. Our results show that the hemR and tonB genes are expressed by S. glossinidius in the tsetse fly. Furthermore, transcription of hemR in Sodalis is repressed in a high-iron environment by the iron-responsive transcriptional regulator Fur. Expression of the S. glossinidius hemR and hemTUV genes in an Escherichia coli strain unable to use heme as an iron source stimulated growth in the presence of heme or hemoglobin as the sole iron source. This stimulation was dependent on the presence of either the E. coli or Sodalis tonB gene. Sodalis tonB and hemR mutant strains were defective in their ability to colonize the gut of tsetse flies that lacked endogenous symbionts, while wild-type S. glossinidius proliferated in this same environment. Finally, we show that the Sodalis HemR protein is localized to the bacterial membrane and appears to bind hemin. Collectively, this study provides strong evidence that TonB-dependent, HemR-mediated iron acquisition is important for the maintenance of symbiont homeostasis in the tsetse fly, and it provides evidence for the expression of bacterial high-affinity iron acquisition genes in insect symbionts.

Comparing Simple Scoring With IRT Scoring of Personality Measures: The Navy Computer Adaptive Personality Scales.

This article analyzes data from U.S. Navy sailors (N = 8,956), with the central measure being the Navy Computer Adaptive Personality Scales (NCAPS). Analyses and results from this article extend and qualify those from previous research efforts by examining the properties of the NCAPS and its adaptive structure in more detail. Specifically, this article examines item exposure rates, the efficiency of item use based on item response theory (IRT)-based Expected A Posteriori (EAP) scoring, and a comparison of IRT-EAP scoring with much more parsimonious scoring methods that appear to work just as well (stem-level scoring and dichotomous scoring). The cutting-edge nature of adaptive personality testing will necessitate a series of future efforts like this: to examine the benefits of adaptive scoring schemes and novel measurement methods continually, while pushing testing technology further ahead.

Salmonella enterica in commercial swine feed and subsequent isolation of phenotypically and genotypically related strains from fecal samples.

The purpose of this study was to determine the occurrence and genotypic relatedness of Salmonella enterica isolates recovered from feed and fecal samples in commercial swine production units. Of 275 feed samples, Salmonella was detected in 10 feed samples that originated from 8 of 36 (22.2%) barns, with a prevalence of 3.6% (10/275 samples). In fecal samples, a prevalence of 17.2% was found at the early finishing stage (1,180/6,880 samples), with a significant reduction in prevalence (7.4%) when pigs reached market age (392/5,321 samples). Of the 280 Salmonella isolates systematically selected for further characterization, 50% of the feed isolates and 55.3% of the isolates of fecal origin showed similar phenotypes based on antimicrobial resistance patterns and serogrouping. About 44% of the isolates were multidrug resistant. Pulsed-field gel electrophoresis (PFGE) genotyping grouped the 46 representative isolates into five genotypic clusters, of which four of the clusters consisted of genotypically related isolates recovered from feed and fecal samples. The occurrence of genotypically related and, in some cases, clonal strains, including multidrug-resistant isolates in commercially processed feed and fecal samples, suggests the high significance of commercial feed as a potential vehicle of Salmonella transmission.

Capsule endoscopy in clinical practice.

Capsule endoscopy is a new technology that is changing the diagnostic endoluminal approach to a variety of disorders and conditions. Initially introduced for the evaluation of the small bowel, endoscopic imaging now can visualize the esophagus and the colon. Any assessment of a new technology should focus on its feasibility, patient tolerance and acceptance, safety, and value in terms of diagnostic or therapeutic use. Since the introduction of capsule endoscopy in 2000, considerable data have become available regarding these issues. This article will review the clinical applications and issues concerning capsule endoscopy utilization.

Do gastroenterologists notify polyp patients that family members should have screening?

OBJECTIVE: The objective of this study was to determine whether patients found to have adenomatous polyps or cancer were notified that their relatives should have screening, due to an increased risk of developing colorectal cancer. METHODS: Consecutive (n = 121) colonoscopy patients from December of 1999 to October of 2001 found to have adenomatous colon polyps or colon cancer formed the study group. Charts were reviewed for documentation of relative notification, and when documentation was not present, study subjects were contacted by telephone. RESULTS: Overall, 71% had data that were able to be evaluated; the remaining 29% were unable to be contacted because of changes of address or phone numbers. Adenomatous polyps were seen in 95%, and cancer seen in 5%. Overall, 30% of the patients were notified: 23 of 82 (28%) in the polyp group and 3 of 4 (75%) in the cancer group. Advanced adenomas or multiple adenomas were noted in 28 of the 82 (34%). Of those, 8 of 28 (29%) were notified. CONCLUSIONS: Gastroenterologists should be aware of the need for increased attention to family notification, especially in those with advanced adenomas or multiple adenomas. Template notification letters may complement the polyp surveillance programs that many colonoscopists use.