Tropical parasitic itch in returned travellers and immigrants from endemic areas.

Itch is the most common skin symptom among tropical parasitic diseases (TPD), but there are limited data about its characteristics in these conditions. In dermatology practices and travellers' health clinics in the developed world, itch is a common complaint among travellers returning from endemic areas, as well among migrants arriving from endemic areas, where they may have been exposed to TPD. Studying aspects of pruritus among TPD may lead to improvements in prompt, accurate diagnosis and management of these conditions. This review examines the major itch-inducing TPDs, including schistosomiasis, echinococcosis, onchocerciasis, scabies, cutaneous larva migrans, larva currens, African trypanosomiasis, dracunculiasis and other causes of travel associated pruritus. We focus on the link between pruritus and other symptoms, aetiology, clinical staging and therapeutic options for these parasitic illnesses. Because some tropical parasitic diseases can present with significant pruritus, we attempt to identify aspects of the pruritus that are characteristic of-or unique to-specific conditions. These diagnostic insights may help clinicians create a rational and focused differential diagnosis and help determine optimal disease management pathways. In this sense, management involves treating the individual, seeking epidemiologically linked cases, preventing recurrences or relapses, and reducing spread of the disease.

Scalp dysesthesia: a neuropathic phenomenon.

Scalp dysesthesia is an abnormal sensation of the scalp in the absence of cutaneous disease. It is characterized by a burning and/or itching sensation and can be related to a variety of neurogenic or psychogenic causes. This condition is extremely bothersome and is also common- especially among the geriatric population, in women, in patients with diabetes mellitus, and patients with psychiatric history. However, despite its prevalence in many populations, there are limited data about its causes and characteristics. Given its limited cutaneous manifestations, it is also easily misdiagnosed and an underrecognized cause of scalp pruritus in the dermatological community. Therefore, education on scalp dysesthesia is paramount to helping physicians identify and provide appropriate treatment for these patients. This review focuses predominantly on the neurogenic causes (with a brief review of psychogenic itch) of scalp dysesthesia and the therapeutics that have been found to be effective for this condition. Neurogenic causes of scalp dysesthesia occur with damage to the central or peripheral pathways of itch sensation, resulting in modification and heightened sensitivity of nerves that result in abnormal sensations in the absence of or out of proportion to external stimuli. A comprehensive review of etiologies is provided here, ranging from lesions to the central nervous system caused by cervical spine disease, trigeminal trophic syndrome, tumor, stroke, and multiple sclerosis, to small-fiber neuropathies caused by diabetes, brow lifts, keloid, and burn scarring. Recently, there have also been reports of scalp dysesthesias associated with post-infectious COVID-19. Treatment options tailored toward disease severity and different causes of disease will also be discussed. By elucidating the different mechanisms and therapeutic treatments of scalp dysesthesia, we hope to provide clinicians with the tools to identify and treat this condition as well as encourage further research into its etiologies and therapeutics.

[Design and application method of a rapid cooling device for burns in field battle training].

At present, there is no special rapid cooling device for burn injury site in field battle training environment. To solve this problem, our research team designed a rapid cooling device for burns in field battle training. Based on the principle of rapid cooling of liquid nitrogen, the device monitors the temperature of the wound surface to regulate the release of liquid nitrogen so as to reduce the wound temperature. The device is simple in design, light in material, small in size, easy to carry, and can be used in various parts of the body. In addition, it is easy to operate and is expected to deliver a rapid cooling effect on the burn injury site to avoid the secondary damage caused by heat conduction to deep tissue.

LncRNA ASB16-AS1 promotes proliferation and inhibits apoptosis of non small cell lung cancer cells by activating the Wnt/ß catenin signaling pathway.

The article "LncRNA ASB16-AS1 promotes proliferation and inhibits apoptosis of non small cell lung cancer cells by activating the Wnt/ß catenin signaling pathway, by L.-J. Tan, J.-T. Liu, M. Yang, T. Ju, Y.-S. Zhang, published in Eur Rev Med Pharmacol Sci 2020; 24 (4): 1870-1876-DOI: 10.26355/eurrev_202002_20365-PMID: 32141556" has been withdrawn from the authors due to due to some inaccuracies (some data cannot be repeated by our further research). The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20365.

LncRNA ASB16-AS1 promotes proliferation and inhibits apoptosis of non small cell lung cancer cells by activating the Wnt/ß catenin signaling pathway.

OBJECTIVE: To detect the expression of long non-coding ribonucleic acid (lncRNA) ASB16-AS1 in non-small cell lung cancer (NSCLC) tissues and cells, and to explore the effect of lncRNA ASB16-AS1 on the biological functions of NSCLC cells. PATIENTS AND METHODS: The expression level of lncRNA ASB16-AS1 in NSCLC tissues and cells was detected via real-time fluorescence quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). The interference sequences of lncRNA ASB16-AS1 were designed and synthesized, and its transfection efficacy was detected by qRT-PCR. After knockdown of lncRNA ASB16-AS1, the proliferation, cell cycle, and apoptosis of NSCLC cells were detected via cell counting kit-8 (CCK-8) assay, colony formation assay, and flow cytometry, respectively. Moreover, the expression changes in the Wnt/ß catenin signaling pathway were detected via Western blotting. RESULTS: LncRNA ASB16-AS1 was upregulated in NSCLC tissues and cells compared with that in paracarcinoma tissues and 16HBE cells. The results of CCK-8 assay and colony formation assay revealed that the silence of lncRNA ASB16-AS1 attenuated the proliferative ability in NSCLC. The results of flow cytometry manifested that the silence of lncRNA ASB16-AS1 arrested the cell cycle in G0/1 phase, and accelerated the apoptosis rate. The key proteins in the Wnt/ß-catenin signaling pathway were regulated by lncRNA ASB16-AS1 in NSCLC. CONCLUSIONS: LncRNA ASB16-AS1 is upregulated in NSCLC tissues and cells, which promotes proliferation and inhibits apoptosis of NSCLC cells through the Wnt/ß-catenin signaling pathway.

The effect of postoperative radiotherapy on the survival of patients with resectable stage III-N2 non-small-cell lung cancer: a systematic review and meta-analysis.

In the potentially resectable cases of stage III-N2 non-small-cell lung cancer (NSCLC), the optimal post-operative treatment regimen for these patients is uncertain and post-operative radiation therapy (PORT) with chemotherapy is typically recommended. Our aim was to reassess the data of PORT on overall survival (OS) and disease-free survival (DFS) in stage III-N2 NSCLC, in order to figure out whether PORT might lead to a moderate improvement in local control and survival besides resection and adjuvant chemotherapy. A comprehensive search strategy was performed in EMBASE, PubMed, and Cochrane Library for relevant studies comparing PORT combined with adjuvant chemotherapy or adjuvant chemotherapy alone on OS and DFS in resectable stage III-N2 NSCLC. Data were extracted to estimate the effects of PORT on OS and DFS. Eleven studies with 8,928 patients were included. This meta-analysis demonstrated a trend in improving OS associated with the use of PORT (HR=0.88; 95% CI, 0.76 to 1.03; p=0.11) and a significantly difference of effect on DFS associated with the use of PORT (HR=0.78; 95% CI, 0.66 to 0.92; p=0.003). In a subgroup analysis on Caucasian patients, there was a statistically significant benefit (HR=0.88; 95% CI, 0.81 to 0.96; p=0.003) on OS for PORT. Our findings demonstrate that in the postoperative treatment for patients with stage III-N2 NSCLC, PORT is associated with improved OS and leads to a significantly increased DFS.

Establishing a model for childhood obesity in adolescent pigs.

OBJECTIVE: Rising worldwide prevalence of obesity and metabolic diseases in children has accentuated the importance of developing prevention and management strategies. The objective of this study was to establish a model for childhood obesity using high-fat feeding of adolescent pigs, as pigs have a longer developmental period and are physiologically more similar to humans than rodents. METHODS: Crossbred pigs were fed a high-fat diet (HFD) or low-fat diet (n = 6/treatment) from postnatal day 49 to 84. On postnatal day 84, an oral glucose tolerance test was performed, jugular blood sampled to determine lipopolysaccharide levels and plasma lipids, intestinal digesta collected to characterize microbial and metabolite composition and back fat and intestinal tissue assayed for gene expression. RESULTS: Five-week HFD increased weight gain and back fat thickness, caused dyslipidaemia and impaired glucose tolerance and increased expression of genes in back fat suggesting inflammation. HFD pigs had distinct proximal colon microbiota with 48% reduction (P < 0.05) in Bacteroidetes and increased expression of pro-inflammatory genes interleukin-18 and tumour necrosis factor in ileum (P < 0.05). CONCLUSIONS: These findings indicate that adolescent pigs should be considered a suitable model for childhood obesity, because short-term HFD feeding is sufficient to induce obesity and glucose intolerance, recapitulating disease characteristics in adolescent pigs.

Resilience is decreased in irritable bowel syndrome and associated with symptoms and cortisol response.

BACKGROUND: Irritable bowel syndrome (IBS) is a stress-sensitive disorder associated with early adverse life events (EALs) and a dysregulated hypothalamic-pituitary-adrenal (HPA) axis. Resilience is the ability to recover and adapt positively to stress but has not been well studied in IBS. The aims of this study are to compare resilience in IBS and healthy controls (HCs) and to assess its relationships with IBS symptom severity, quality of life (QOL), EALs, and HPA axis response. METHODS: Two hundred fifty-six subjects (154 IBS, 102 HCs) completed questionnaires for resilience (Connor-Davidson Resilience Scale [CD-RISC] and Brief Resilience Scale [BRS]), IBS symptoms, IBS-QOL, and EALs. Ninety-six of these subjects had serial serum adrenocorticotropic hormone (ACTH) and cortisol levels to exogenous corticotrophin-releasing hormone (CRH) and ACTH measured. The relationship between IBS status, resilience, and other variables of interest was assessed by regression analysis after adjusting for demographics and neuroticism, a predictor of resilience. KEY RESULTS: Resilience was significantly lower in IBS compared to HCs (CD-RISC: 72.16±14.97 vs 77.32±12.73, P=.003; BRS: 3.29±0.87 vs 3.93±0.69, P<.001); however, only BRS was significant after controlling for neuroticism (P=.001). Lower BRS scores were associated with greater IBS symptom severity (P=.002), poorer IBS-QOL (P<.001), and a higher number of EALs (P=.01). There was a significant interaction between BRS resilience and IBS status for ACTH-stimulated cortisol response (P=.031); more resilient IBS subjects had lower cortisol response, and more resilient HCs had higher cortisol response. CONCLUSIONS AND INFERENCES: Lower resilience is associated with IBS status, worse IBS symptom severity, lower IBS-QOL, greater EALs, and stress hyperresponsiveness.

Separation of Two Distinct O-Glycoforms of Human IgA1 by Serial Lectin Chromatography Followed by Mass Spectrometry O-Glycan Analysis.

Human immunoglobulin A1 (IgA1), which carries four to six mucin-type O-glycans (O-glycans) on its hinge region (HR), is the most abundant O-glycoprotein in plasma or serum. While normal O-glycans from hematopoietic-originated cells are core 1-based complex structures, many reports showed that the IgA1 from patients with IgA nephropathy (IgAN) carries undergalactosylated or truncated O-glycans such as the Tn antigen and its sialylated version the SialylTn (STn) antigen on the HR. Yet, there is still a debate whether Tn/STn on the HR of IgA1 is specific to the IgA1 from patients with IgAN since these antigens have also been seen in serum IgA1 of healthy individuals. An additional question is whether the O-glycans at all sites on the two HRs of one IgA1 molecule are homogeneous (either all normal or all Tn/STn) or heterogeneous (both normal and Tn/STn O-glycans). To address these questions, we conducted a systematic study on the O-glycans of plasma IgA1 from both IgAN patients and healthy controls using serial HPA and PNA lectin chromatography followed by western blotting and further analysis of O-glycans from HPA-bound and PNA-bound IgA1 fractions by mass spectrometry. Unexpectedly, we found that a variable minor fraction of IgA1 from both IgAN patients and healthy controls had Tn/STn antigens, and that the O-glycoprotein IgA1 molecules from most samples had only two distinct O-glycoforms: one major glycoform with homogeneous normal core 1-based O-glycans and one minor glycoform with homogeneous Tn/STn antigens. These results raised a serious question about the role of Tn/STn antigens on IgA1 in pathogenesis of IgAN, and there is a demand for a practical methodology that any laboratory can utilize to analyze the O-glycans of IgA1. Herein, we describe the methodology we developed in more detail. The method could also be applied to the analysis of any other O-glycosylated proteins.

Clinical, Hormonal, and Genetic Evaluation of Idiopathic Nonobstructive Azoospermia and Klinefelter Syndrome Patients.

To investigate the clinical, hormonal, and genetic factors in infertile men with idiopathic nonobstructive azoospermia (NOA) or azoospermic Klinefelter syndrome (KFS), a total of 556 and 96 patients, respectively, were included in this study. All patient samples were analyzed cytogenetically. Serum reproductive hormone levels were measured. Microdeletions in the azoospermia factor (AZF) region of the Y chromosome were detected by multiplex PCR using 16 specific sequence-tagged sites. FSH and LH levels in both NOA and KFS patients were significantly higher than the normal range, and the testosterone level in KFS patients was significantly lower. Ninety-two (95.8%) of the KFS patients showed non-mosaic 47,XXY karyotypes and 47,XXY,inv(9)(p11.1q13); the other KFS patients had mosaic karyotypes of 47,XXY/46,XY, 47,XXY/46,XX, and 47,XXY/48,XXXY/46,XX. Among the 556 idiopathic NOA patients with normal karyotypes, 67 (12.05%) had microdeletions in the AZF region of the Y chromosome. Microdeletions were most frequently detected in the AZFc region, followed by AZFa, AZFb, AZFbc, and partial AZFc deletions. However, Y chromosome microdeletions were not found in any of the azoospermic KFS patients. In view of the hormonal and genetic abnormalities in infertile men with idiopathic NOA and with azoospermic KFS, genetic testing for karyotype, Y chromosome microdeletions, and hormonal parameters is advocated.

Next-generation sequencing of Chinese stage IV lung cancer patients reveals an association between EGFR mutation status and survival outcome.

Large-scale genomic characterization of non-small cell lung cancer (NSCLC) has revealed several putative oncogenic driver mutations that may constitute druggable therapeutic targets. However, there are little data to suggest that such gene alterations have clinical relevance. Over 12 consecutive months, tumor biopsy samples from 80 patients with stage IV NSCLC were analyzed for mutations in selected exons of 508 cancer-related genes using next-generation sequencing. From 85 specimens referred for genomic characterization, 80 (94%) specimens were successfully genotyped, and all had identifiable somatic alterations. Epidermal growth factor receptor (EGFR) and TP53 genes contained the highest frequency of observed mutations (65% and 40%, respectively) in the stage IV NSCLC cases. Notably, patients with EGFR mutations showed a significantly shorter survival time compared with patients expressing wild-type EGFR (p = 0.0053). Moreover, of the 32 patients harboring EGFR mutations, EGFR-L858R mutant patients showed a significantly shorter survival time compared with patients with other EGFR mutations (p = 0.036). In conclusion, tumors from stage IV NSCLC patients harbor characteristic gene alterations, of which EGFR L858R in particular appears to be a poor prognostic factor for overall survival.

MMP-9 is increased in the pathogenesis of gastric cancer by the mediation of HER2.

Human epidermal growth factor receptor 2 (HER2) overexpression is not only closely associated with the tumor growth, but is also related to tumor invasion. We here aimed to investigate the mechanism of HER2 mediation in the pathogenesis of gastric cancer. The human gastric cancer cell lines SGC-7901, MKN-45, AGS, the immortalized cell line GES-1 derived from normal gastric mucosa. Cell transfection and selection of stable cell lines and the gene and protein levels of HER2 and Matrix metalloproteinase-9 (MMP-9) were examined to determine the molecular relationship between them in the pathogenesis of gastric cancer. The human gastric cancer cell lines SGC-7901, MKN-45, AGS, the immortalized cell line GES-1 derived from normal gastric mucosa. Cell transfection and selection of stable cell lines and the gene and protein levels of HER2 and MMP-9 were examined to determine the molecular relationship between them in the pathogenesis of gastric cancer. We demonstrated that vector-based shRNA significantly knocked down the expression of HER2 and considerably inhibited both the migration and invasion of gastric cancer cells. HER2 knockdown resulted in the downregulation of the expression of MMP-9, whereas HER2 overexpression improved the transcription of MMP-9 through the activation of an MMP-9 promoter. The promoter region of MMP-9 between -2500 and -2000 bp was found to be crucial for the upregulation of HER2-mediated transcription. Furthermore, a truncated promoter (-70 to +63) did not display any transcriptional activity. Cell invasion activity was almost completely inhibited when MMP-9 was knocked down. Conversely, the overexpression of MMP-9 partly rescued the invasion ability of cell strains with knockdown HER2. These findings help further understanding of the molecular mechanisms through which HER2 promotes malignancy, and suggest that targeting both HER2 and MMP-9 may be required to effectively block HER2 signaling in gastric cancer therapy.

A semiautomated approach for artefact removal in serial tissue cryosections.

Thinly sliced serial tissue sections of an organ can be imaged using optical microscopy at a resolution detailing individual cells. When the tissue sections are first subjected to in situ hybridization or immunohistochemistry, these data sets can be analysed for changes in gene expression and gene products. Such spatial information is important for understanding the functional effects of experimental or environmental challenges to the organism. However, a critical step in analysing these data sets is mitigating artefacts that result from the preparation of the tissue sections. In this paper, we describe an automated method with manual validation tools that together enable detecting and addressing artefacts including dust particles and air bubbles.

Semi-isometric registration of line features for flexible fitting of protein structures.

In this paper, we study a registration problem that is motivated by a practical biology problem - fitting protein structures to low-resolution density maps. We consider registration between two sets of lines features (e.g., helices in the proteins) that have undergone not a single, but multiple isometric transformations (e.g., hinge-motions). The problem is further complicated by the presence of symmetry in each set. We formulate the problem as a clique-finding problem in a product graph, and propose a heuristic solution that includes a fast clique-finding algorithm unique to the structure of this graph. When tested on a suite of real protein structures, the algorithm achieved high accuracy even for very large inputs containing hundreds of helices.

Use of sequential ASE extraction to evaluate the bioavailability of DDT and its metabolites to wheat roots in soils with various organic carbon contents.

An accelerated solvent extraction (ASE) procedure using water, n-hexane and a mixture of n-hexane and acetone as solvents in sequence was developed and tested to evaluate the bioavailability of DDT and its metabolites including p,p'-DDT, o,p'-DDT, p,p'-DDE, and p,p'-DDD (SigmaDDTs) to wheat uptake from soils characterized by varied organic carbon contents. Results indicated that the extractability of SigmaDDTs with water was enhanced considerably in the presence of water soluble organic carbon (WSOC), while the amount of SigmaDDTs extracted with n-hexane was negatively correlated to the content of water insoluble organic carbon (WIOC). The interaction between SigmaDDTs and WIOC also reduced the bioavailability of the pesticides to wheat roots during uptake. There was a good positive correlation between the amount of SigmaDDTs extracted by n-hexane and the amount of SigmaDDTs accumulated in wheat roots, suggesting some potential for the use of the n-hexane ASE-extracted fraction as an indicator of SigmaDDTs' bioavailability to plant uptake. As such, the three sequentially extracted fractions may be viewed as representing the mobile, bioavailable, and fixed pools of SigmaDDTs in the soil.

Automated characterization of gene expression patterns with an atlas of the mouse brain.

A spatio-temporal map of gene activity in the brain would be an important contribution to the understanding of brain development, disease, and function. Such a resource is now possible using high-throughput in situ hybridization, a method for transcriptome-wide acquisition of cellular resolution gene expression patterns in serial tissue sections. However, querying an enormous quantity of image data requires computational methods for describing and organizing gene expression patterns in a consistent manner. In addressing this, we have developed procedures for automated annotation of gene expression patterns in the postnatal mouse brain.

The efficacy of oral vaccination of mice with alginate encapsulated outer membrane proteins of Pasteurella haemolytica and One-Shot.

The goal of this study was to examine the efficacy of oral delivery of alginate encapsulated outer membrane proteins (OMP) of Pasteurella haemolytica and a commercial One-Shot vaccine in inducing protection in mice against lethal challenge with virulent P. haemolytica. We examined two alginate microsphere formulations and compared them with oral unencapsulated and subcutaneously administered vaccines. Alginate microspheres were made by the emulsion-cross-linking technique. They were examined for size, hydrophobicity, and antigen loading efficiency before they were used in the study. Mice were vaccinated by administering 200 microg of antigens in 200 microl of microspheres suspension orally or subcutaneously. One group of mice received blank microspheres and a second group was given unencapsulated antigen orally. A third and a fourth group received different formulations of alginate encapsulated antigens by oral administration. Three groups received subcutaneous inoculations (alginate encapsulated, non-adjuvanted and unencapsulated antigens, and adjuvanted One-Shot), and one group received water (naïve group). Mice were vaccinated orally for four consecutive days and challenged with P. haemolytica 5 weeks after the first vaccination. Weekly serum and feces samples were assayed for antigen specific antibodies. The number of dead mice in each group 4 days post challenge was used to compare the efficacy of the various vaccination groups. The mean volume sizes of blank alginate microsphere formulations A, and AA were 15.9, 16 and 9.2 microm, respectively. Hydrophobicity of the microspheres was evaluated by measuring contact angle on a glass slide coated with the microspheres. The contact angles on A and AA were 37.8 and 74.3 degrees, respectively. Antigen concentration in a 1:1 w/w suspension of microspheres in water was 0.9 mg/ml. Rate of death for the blank group was 42.8% whereas for groups vaccinated with antigens encapsulated in A and AA the death rates were 40 and 33.33%, respectively. The death rate in mice vaccinated with unencapsulated antigens was 55.6%. Groups vaccinated by subcutaneous inoculation showed the lowest death rate. These results show that encapsulating OMP and One-Shot in alginate microspheres improves their performance as an oral vaccine.

Opposing changes in N-acetylglucosaminyltransferase-V and -III during the cell cycle and all-trans retinoic acid treatment of hepatocarcinoma cell line.

The changes in N-acetylglucosaminyltransferase-V and -III (GnT-V, GnT-III) during the cell-cycle of synchronized 7721 human hepatocarcinoma cell line were investigated. Using an HPLC method to assay GnT and flow cytometry (FCM) for cell cycle analysis, it was found that GnT-V showed the highest activity, but GnT-III reached the lowest activity when G(2)/M cells were most abundant. In contrast, GnT-V declined to the minimum while GnT-III elevated to maximum when G(0)/G(1) cells were most predominant. The opposing changes were more obvious when the activities of GnT-V and GnT-III were expressed as relative activities (activity of GnT-V or GnT-III/the sum of activities of GnT-V plus GnT-IV plus GnT-III). These opposing changes of GnT-V and GnT-III during the cell cycle might result from the different regulatory mechanisms of GnT-V and GnT-III expression in the cell cycle. The alterations in the structures of cell surface N-glycans were compatible with the changes of the activities of GnTs. The results from immunocytochemistry and Northern blot showed that the protein and mRNA contents of GnT-V were not significantly changed during the cell cycle. The activity of a cell cycle regulating protein kinase, p34(cdc2) kinase, correlated to the activity of GnT-V. These findings suggested that the change of GnT-V activity in cell cycle was not the consequence of the alteration of gene transcription or enzyme protein synthesis, but might be caused by the post-translational regulation. The decrease in GnT-V and the corresponding increase in GnT-III activities were also found after the cells were treated with all-trans retinoic acid (ATRA), and the mechanism of this might be different from that in the cell cycle.