Short peptidoglycan recognition protein 5 modulates immune response to bacteria in Indian major carp, Cirrhinusmrigala.

Peptidoglycan recognition proteins (PGRPs) function in host antibacterial responses by recognizing bacterial peptidoglycan (PGN). In the present study, a short pgrp5 (named mpgrp5) was identified in Cirrhinus mrigala (mrigal). The full-length cDNA of the mpgrp5 gene was 1255 bp, containing an open reading frame of 746 bp encoding a protein of 248 amino acids. The predicted protein contained the typical Pgrp/amidase domain, conserved Zn2+, and PGN binding residues. The phylogenetic analysis revealed that the mpgrp5 is closely related to Pgrps reported in Labeo rohita, Cyrinus carpio, and Ctenopharyngodon idella. The ontogenetic expression of mpgrp5 was highest at 7 days post-hatching (dph) and its possible maternal transfer. mpgrp5 was constitutively expressed in all tissues examined, with the highest expression observed in the intestine. Furthermore, mpgrp5 was found upregulated in mrigal post-challenge in a time-dependent manner at 6hpi in the liver (3.16 folds, p < 0.05) and kidney (2.79 folds, p < 0.05) and at 12hpi in gill (1.90 folds, p < 0.01), skin (1.93 folds, p < 0.01), and intestine, (2.71 folds, p < 0.05) whereas at 24hpi in spleen (4.0 folds, p < 0.01). Our results suggest that mpgrp5 may play an important role in antibacterial immune response from early life stages in mrigal.

Evaluation of a Case Series of Patients With Generalized Pustular Psoriasis in the United States.

IMPORTANCE: Generalized pustular psoriasis (GPP) is a chronic, orphan disease with limited epidemiological data. OBJECTIVE: To describe the clinical characteristics, treatments, longitudinal disease course, and disease-specific health care utilization among patients with GPP across the United States. DESIGN, SETTING, AND PARTICIPANTS: A retrospective longitudinal case series involving 95 adults who met the European Rare and Severe Psoriasis Expert Network consensus definition for GPP and were treated at 20 US academic dermatology practices between January 1, 2007, and December 31, 2018. MAIN OUTCOMES AND MEASURES: The primary outcome is to describe the patient characteristics, associated medical comorbidities, treatment patterns complications, and GPP-specific health care utilization. RESULTS: Sixty-seven of 95 patients (70.5%) were women (mean age, 50.3 years [SD, 16.1 years]). In the initial encounter, 35 patients (36.8%) were hospitalized and 64 (67.4%) were treated with systemic therapies. In total, more than 20 different systemic therapies were tried. During the follow-up period, 19 patients (35.8%) reported hospitalizations at a median rate of 0.5 hospitalizations per year (IQR, 0.4-1.6). Women had a decreased risk of an emergency department or hospital encounter (odds ratio, 0.19; 95% CI, 0.04-0.83). CONCLUSIONS AND RELEVANCE: Generalized pustular psoriasis is a rare, chronic disease without standard treatment and is associated with continued health care utilization over time.

Evaluation of a Case Series of Patients With Palmoplantar Pustulosis in the United States.

IMPORTANCE: Palmoplantar pustulosis (PPP) is a is a chronic, orphan disease with limited epidemiological data. OBJECTIVE: To describe the clinical characteristics, treatments, longitudinal disease course, and health care utilization in adults with PPP across the US. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, longitudinal case series from 20 academic dermatology practices in the US included a consecutive sample of 197 adults who met the European Rare and Severe Psoriasis Expert Network consensus definition for PPP between January 1, 2007, and December 31, 2018. Data analysis was performed June 2020 to December 2020. MAIN OUTCOMES AND MEASURES: The primary outcome was to describe the patient characteristics, associated medical comorbidities, treatment patterns, complications, and PPP-specific health care utilization. RESULTS: Of 197 patients, 145 (73.6%) were female, and the mean (SD) age at presentation was 53.0 (12.6) years, with a mean (SD) follow-up time of 22.1 (28.0) months. On initial presentation, 95 (48.2%) patients reported skin pain, and 39 (19.8%) reported difficulty using hands and/or feet. Seventy patients (35.5%) were treated with systemic treatments, and use of more than 20 different systemic therapies was reported. In patients with at least 6 months of follow-up (n = 128), a median (IQR) of 3.7 (4-10) dermatology visits per year were reported; 24 (18.8%) patients had 5 or more visits during the study period. CONCLUSIONS AND RELEVANCE: In this case series, PPP was associated with persistent symptoms, continued health care utilization, and a lack of consensus regarding effective treatments, emphasizing the unmet medical need in this population. Additional research is necessary to understand treatment response in these patients.

Does location matter? Geographic variations in healthcare resource use for atopic dermatitis in the United States.

BACKGROUND: It is unknown which region of the U.S. offers the best and worst access to care for atopic dermatitis (AD). METHODS: We conducted a cross-sectional study using the Medical Expenditure Panel Survey (MEPS) from 1996 to 2015 to compare healthcare resource use and cost of AD among U.S. census regions. We conducted multivariable regression analyses adjusting for clinicodemographic factors to evaluate regional differences in healthcare resource use and cost per patient per year (PPPY) in terms of ambulatory visits, ED visits, and medications directly attributable to AD. RESULTS: An estimated total of 6,348,578 (95% CI: 5,944,553-6,752,803) AD patients (weighted) were pooled. Compared to the remainder of the country, Midwest AD patients utilized the fewest ambulatory visits (0.55 versus 0.75 visits PPPY; p = .035). The proportion of patients with ≥1 ED visits was highest in the Midwest (7.1%), followed by the South (5.4%), Northeast (4.8%), and West (1.4%). Within the Midwest AD population, those with no ambulatory visits per year utilized nearly three times more ED visits when compared with those with one or more ambulatory visits per year (0.11 versus 0.04 visits PPPY; p = .019). CONCLUSION: Our results suggest that Midwest AD patients have differential access to outpatient care, which may be resulting in higher ED usage.

Erythema elevatum et diutinum as a systemic disease.

Erythema elevatum et diutinum (EED) is a rare, chronic dermatosis. It has been associated with extracutaneous findings, including arthralgias, scleritis, panuveitis, peripheral ulcerative keratitis, oral and penile ulcers, and neuropathy. Additionally, EED is connected with various systemic diseases, including HIV, IgA paraproteinemia, myelomas, neutrophilic dermatoses, and inflammatory bowel diseases. The presence of such extracutaneous manifestations in EED patients suggests that EED may be a multiorgan entity. Extracutaneous manifestations in EED may involve deposition of circulating immune complexes; thus, patients with EED should be evaluated for systemic manifestations to ensure targeted management.

Economic burden of cutaneous infections in children and adults with atopic dermatitis.

BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) is a chronic, inflammatory disease affecting both children and adults. AD is associated with multiple comorbidities and complications. In particular, AD patients are susceptible to developing cutaneous infections. Studies show that comorbidities have contributed significantly to increased health care utilization and costs in AD. However, evidence regarding the degree to which this increased health care utilization and expenditure in AD is attributable to cutaneous infections is lacking. The aim of this study was to assess the impact of skin infections on health care utilization and expenditures among patients with atopic dermatitis. METHODS: This cross-sectional study examined health care utilization and expenditures for AD patients of all ages with and without skin infections in the United States using the nationally representative 1996-2015 Medical Expenditure Panel Survey (MEPS) data. RESULTS: In this study, a total of 4 825 668 (weighted) patients had a diagnosis of AD (mean age 5.7). Of these, 776 753 patients (16%) experienced skin infections (mean age 4.4). Compared to AD patients without skin infections, those with skin infections had more frequent visits to ambulatory clinics (P = 0.001) and the emergency department (P = 0.011), and increased hospitalization (P = 0.010), after adjustments for demographic and clinical factors. AD patients with skin infections were also given 3.3 more prescriptions (P < 0.0001). AD patients with skin infections incurred significantly greater health care costs, which included an additional $351/patient/year for ambulatory visits (P < 0.0001) and an additional $177/patient/year for prescription medications (P < 0.0001). CONCLUSIONS: Atopic dermatitis patients with cutaneous infections incurred significantly greater health care utilization and expenditures than those without cutaneous infections.

Association Between Atopic Dermatitis and Suicidality: A Systematic Review and Meta-analysis.

Importance: Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with numerous psychiatric comorbidities. However, the association between AD and suicidality has not been well established. Objective: To synthesize the available literature to evaluate the association between AD and suicidality. Data Source: The protocol was prospectively registered in the PROSPERO database (CRD42018105291). Study Selection: Per PRISMA guidelines, PubMed, Embase, PsycINFO, and Cochrane databases were systematically searched for relevant articles published from 1946 to May 25, 2018. The search criteria for PubMed were as follows: (dermatitis, atopic [MeSH] OR eczema [MeSH]) AND (suicidal ideation [MeSH] OR suicide, attempted [MeSH] OR suicide [MeSH] OR suicidality OR suicidal behavior). The search criteria for Embase, PsycINFO, and Cochrane were as follows: (atopic dermatitis OR eczema) AND (suicidal ideation OR suicide attempt OR suicide OR suicidality OR suicidal behavior). Data Extraction and Synthesis: This systematic review and meta-analysis performed in an academic medical setting included observational studies that evaluated suicidal ideation, suicide attempts, and completed suicide among patients with AD. Main Outcome and Measure: The quality of included studies was assessed using the Newcastle-Ottawa Scale for observational studies. Results: The analysis identified 15 studies with a total of 4 770 767 participants, of whom 310 681 were patients with AD (52.7% female) and 4 460 086 served as controls (50.9% female). In the meta-analyses, patients with AD were 44% more likely to exhibit suicidal ideation (pooled odds ratio, 1.44; 95% CI, 1.25-1.65) and 36% more likely to attempt suicide (pooled odds ratio, 1.36; 95% CI, 1.09-1.70) compared with patients without AD. Studies investigating completed suicides in patients with AD had inconsistent results. Conclusions and Relevance: Results of this study suggest that patients with AD are at significantly increased risk of suicidal ideation and suicide attempts. It is important for dermatology providers to be aware of this risk, screen for suicidality in patients with AD, and make mental health referrals when necessary.

Preliminary investigations on the role of Drp-1 dependent mitochondrial fission in attenuating RLR downstream signaling during nervous necrosis virus infection.

Member of the dynamin family of large GTPases, dynamin-related protein 1 (Drp1) dependent mitochondrial fission is an intricate process regulating both cellular and organ dynamics. Present study shows that NNV perturbs mitochondrial dynamics by promoting Drp-1 dependent mitochondrial fission, which attenuates MAVS mediated downstream signaling. NNV infected SISS cells revealed induction in Drp1 expression and subsequent translocation into mitochondria. The level of MAVS expression was up-regulated over a period of 24 hpi and declined with the progression of NNV infection at 48 and 72 hpi confirmed by western blot and mRNA transcript analysis. Drp-1 displayed its association with fragmented mitochondria and the transcript abundance was significant post infection along with Mff. Expression levels of IRF-3 IFN-1 and Mx followed a similar pattern with abundant expression at 48 hpi and diminished expression during the further period. Importantly, silencing of Drp1 caused significant elevation in the RLR downstream molecules and reduction in viral RNA expression. These results suggest that NNV-induced mitochondrial fission serve to attenuate host RLR signaling. This provides an illustration of host-pathogen interaction in which the virus evades innate immunity by enhancing mitochondrial fission and perturbs MAVS, and the downstream molecules.

Removal of gadolinium, a neutron poison from the moderator system of nuclear reactors.

Gadolinium as gadolinium nitrate is used as neutron poison in the moderator system for regulating and controlling the power generation of Pressurized Heavy Water Reactors (PHWR) and proposed to be used in Advanced Heavy Water Reactors (AHWR) owing to its high neutron absorption cross section. Removal of the added gadolinium nitrate (Gd3+ and NO3-) from the system after its intended use is done using ion exchange resins. In the present investigation, attempts have been made to optimize the ion exchange process for generation of low radioactive waste and maximize utilization of the ion exchange resins by employing different types of resins and different modes of operation. The investigations revealed that use of mixed bed (MB) resin column consisting of Strong Acid Cation (SAC) resin and Strong Base Anion (SBA) resin followed by SAC resin column is efficient in removing the Gd3+ and NO3- from the system besides maintaining the pH of the moderator system in the desirable regime, where gadolinium does not get precipitated as its hydroxide.

Molecular characterization, ontogeny and expression profiling of mitochondrial antiviral signaling adapter, MAVS from Asian seabass Lates calcarifer, Bloch (1790).

Mitochondrial antiviral signaling protein (MAVS), an innate immune signaling adapter coordinates the signals received from two independent cytosolic pathogen recognition receptors (RIG-1 and MDA5) to induce antiviral genes. In the present study the MAVS gene of Lates calcarifer (LcMAVS) was cloned and characterized. The complete cDNA sequence of LcMAVS was 3160 bp and encodes a poly peptide of 577 amino acids. Structural analysis of LcMAVS revealed an N-terminal CARD-like domain, central proline-rich domain and a C-terminal transmembrane domain. Phylogenetic analysis indicated that LcMAVS exhibited the closest relationship to P. olivaceous MAVS. LcMAVS was ubiquitously expressed in all tested tissues of healthy fish viz., brain, gill, heart, liver, spleen, kidney and intestine, with highest transcript level in spleen. The mRNA transcript level of LcMAVS in different developmental stages showed constitutive expression in all the stages tested suggesting the maternal transfer of the gene. Significant up regulation in MAVS expression was observed post nervous necrosis virus (NNV) challenge in vivo in all the selected tissues. Further, time course analysis showed that LcMAVS transcripts significantly increased in the brain and spleen tissues after NNV infection. These findings provide useful information for further elucidating the function of LcMAVS in antiviral innate immune response against NNV in Asian seabass.

Expression Profiling of WSSV ORF 199 and Shrimp Ubiquitin Conjugating Enzyme in WSSV Infected Penaeus monodon.

White spot syndrome virus (WSSV) is one of the major viral pathogens affecting shrimp aquaculture. Four proteins, WSSV199, WSSV 222, WSSV 249 and WSSV 403, from WSSV are predicted to encode a RING-H2 domain, which in presence of ubiquitin conjugating enzyme (E2) in shrimp can function as viral E3 ligase and modulate the host ubiquitin proteasome pathway. Modulation of host ubiquitin proteasome pathway by viral proteins is implicated in viral pathogenesis. In the present study, a time course expression profile analysis of WSSV Open Reading Frame (ORF) 199 and Penaeus monodon ubiquitin conjugating enzyme (PmUbc) was carried out at 0, 3, 6, 12, 24, 48 and 72 h post WSSV challenge by semi-quantitative RT-PCR as well as Real Time PCR. EF1α was used as reference control to normalize the expression levels. A significant increase in PmUbc expression at 24 h post infection (h.p.i) was observed followed by a decline till 72 h.p.i. Expression of WSSV199 was observed at 24 h.p.i in WSSV infected P. monodon. Since the up-regulation of PmUbc was observed at 24 h.p.i where WSSV199 expression was detected, it can be speculated that these proteins might interact with host ubiquitination pathway for viral pathogenesis. However, further studies need to be carried out to unfold the molecular mechanism of interaction between host and virus to devise efficient control strategies for this chaos in the shrimp culture industry.

Effect of Emblica officinalis, Phyllanthus amarus and Picrorrhiza kurroa on N-nitrosodiethylamine induced hepatocarcinogenesis.

Extracts of Emblica officinalis (EO), Phyllanthus amarus (P. amarus) and Picrorrhiza kurroa (P. kurroa) significantly inhibited hepatocarcinogenesis induced by N-nitrosodiethylamine (NDEA) in a dose dependent manner. The anticarcinogenic activity of these extracts were evaluated by their effect on tumour incidence, levels of carcinogen metabolizing enzymes, levels of liver cancer markers and liver injury markers. Animals treated with NDEA alone showed 100% tumour incidence and significantly elevated tissue levels of drug metabolizing enzymes such as glutathione S-transferase (GST) and aniline hydroxylase (AH). Treatment of extracts significantly reduced these levels. Levels of gamma-glutamyl transpeptidase (GGT) were also found to be elevated both in serum and tissues of tumour bearing animals, while they were significantly reduced in the treated group. Similar reduction was seen in tissue levels of reduced glutathione. Serum levels of lipid peroxide (LPO), alkaline phosphatase (ALP) and glutamate pyruvate transaminase (OPT), which are markers of liver injury, were also elevated. Morphology of liver tissue and levels of marker enzymes indicated that these extracts offered protection against chemical carcinogenesis.