Treatment of Isolated Gastric Crohn's Disease with Inhaled Corticosteroids

Isolated gastric Crohn's disease is unusual and a rare cause of pyloric outlet obstruction. If medical therapy is ineffective, patients may require surgery to relieve gastric outlet obstruction. Herein we describe a patient with isolated gastric Crohn's disease with pyloric outlet obstruction who was steroid-dependent and had a relapse despite receiving biologic and immunomodulatory therapy, but ultimately responded to topical treatment with inhaled corticosteroids

Discovery of Cyclotron Resonance Features in the Soft Gamma Repeater SGR 1806-20

We report evidence of cyclotron resonance features from the Soft Gamma Repeater SGR 1806-20 in outburst, detected with the Rossi X-ray Timing Explorer in the spectrum of a long, complex precursor that preceded a strong burst. The features consist of a narrow 5.0 keV absorption line with modulation near its second and third harmonics (at 11.2 keV and 17.5 keV respectively). The line features are transient and are detected in the harder part of the precursor. The 5.0 keV feature is strong, with an equivalent width of ~ 500 eV and a narrow width of less than 0.4 keV. Interpreting the features as electron cyclotron lines in the context of accretion models leads to a large mass-radius ratio (M/R > 0.3 M_sun/km) that is inconsistent with neutron stars or that requires a low (5-7)x10^{11} G magnetic field that is unlikely for SGRs. The line widths are also narrow compared with those of electron cyclotron resonances observed so far in X-ray pulsars. In the magnetar picture, the features are plausibly explained as ion cyclotron resonances in an ultra-strong magnetic field that have recently been predicted from magnetar candidates. In this view, the 5.0 keV feature is consistent with a proton cyclotron fundamental whose energy and width are close to model predictions. The line energy would correspond to a surface magnetic field of 1.0x10^{15} G for SGR 1806-20, in good agreement with that inferred from the spin-down measure in the source.Comment: Published in the 2002 July 20 issue of the Astrophysical Journal Letters, 574, L5

Discovery of a New Transient Magnetar Candidate: XTE J1810-197

We report the discovery of a new X-ray pulsar, XTE J1810-197. The source was serendipitously discovered on 2003 July 15 by the Rossi X-ray Timing Explorer (RXTE) while observing the soft gamma repeater SGR 1806-20. The pulsar has a 5.54 s spin-period and a soft spectrum (photon index ~ 4). We detect the source in earlier RXTE observations back to 2003 January. These show that a transient outburst began between 2002 November 17 and 2003 January 23 and that the pulsar has been spinning down since then, with a high rate Pdot ~ 10^-11 s/s showing significant timing noise, but no evidence for Doppler shifts due to a binary companion. The rapid spin-down rate and slow spin-period imply a super-critical magnetic field B=3x10^14 G and a young characteristic age < 7600 yr. These properties are strikingly similar to those of anomalous X-ray pulsars and soft gamma repeaters, making the source a likely new magnetar. A follow-up Chandra observation provided a 2".5 radius error circle within which the 1.5 m Russian-Turkish Optical Telescope RTT150 found a limiting magnitude of R_c=21.5, in accord with other recently reported limits. The source is present in archival ASCA and ROSAT data as well, at a level 100 times fainter than the \~ 3 mCrab seen in 2003. This suggests that other X-ray sources that are currently in a state similar to the inactive phase of XTE J1810-197 may also be unidentified magnetars awaiting detection via a similar activity.Comment: Submitted to ApJL; 4 pages; 4 figure

A new low molecular mass alkaline cyclodextrin glucanotransferase from Amphibacillus sp. NRC-WN isolated from an Egyptian soda lake

Background: Cyclodextrin glucanotransferase (CGTase) is one of the most industrially important enzymes used in the commercial production of cyclodextrins (CDs). Alkaliphilic bacteria have attracted much interest in the last few decades because of their ability to produce extracellular enzymes that are active and stable at high pH values. Here, we report the isolation of a new CGTase from alkaliphilic bacteria collected from Egyptian soda lakes and describe the purification and biochemical characterization of this CGTase. Results: Screening for CGTase-producing alkaliphilic bacteria from sediment and water samples collected from Egyptian soda lakes located in the Wadi Natrun valley resulted in the isolation of a potent CGTase-producing alkaliphilic bacterial strain, designated NRC-WN. Strain NRC-WN was belonging to genus Amplibacullus by 16S rDNA sequence analysis (similarity: ca. 98%). Among the tested nitrogen and carbon sources, peptone (0.15%, w/v) and soluble starch (0.4%, w/v) allowed maximal CGTase production by Amphibacillus sp. NRC-WN. CGTase was successfully purified from Amphibacillus sp. NRC-WN up to 159.7-fold through a combination of starch adsorption and anion exchange chromatography, resulting in a yield of 84.7%. SDS-PAGE analysis indicated that the enzyme was purified to homogeneity and revealed an estimated molecular mass of 36 kDa, which makes it one of the smallest CGTases reported in the literature. The purified enzyme exhibited maximum activity at 50oC and was stable up to 70oC, retaining 93% of its initial activity after treatment for 1 hr. Furthermore, Ca2+ ions (10 mM) significantly enhanced the thermal stability of the CGTase. The purified enzyme was active and stable over a wide pH range, showing maximal activity at pH 9.5. The enzyme was significantly stimulated by Zn2+, Ca2+ and Co2+ but was completely inhibited in the presence of Fe3+ and mercaptoethanol. The Km and Vmax values of the purified CGTase were estimated to be 0.0434 mg/ml and 3,333.3 mg \u3b2-CD/ml/min, respectively. \u3b2-CD was the predominant product of starch degradation by the Amphibacillus sp. NRC-WN CGTase, followed by \u3b1-and \u3b3-CDs. Conclusions: A new low molecular mass alkaline CGTase was purified from a newly identified alkaliphilic Amphibacillus sp. NRC-WN isolate from the Egyptian soda lakes. The enzyme showed promising thermal and pH stability and a high affinity toward starch as a natural substrate

HEPATITIS C VIRUS GENOTYPING IN CHRONIC HEPATITIS C PATIENTS

Chronic hepatitis C virus infection is a massive worldwide healthcare burden with estimated costs in the USA alone of over $5 billon per annum. The virus has a 9.5kb positive sense single-stranded RNA genome with striking heterogeneity between isolates, which has led to it being divided into 6 genotypes and more than 50 subtypes and many quasispecies that has been arisen due to the infidelity of the viral polymerase, which lacks of a proofreading function. The virus exists as a range of related but not identical species at the quasispecies. In each infected individual, HCV circulates as a quasispecies in which the population consists of a number of closely related but distinct genetic species. The distribution of the genotype might be influenced by the mode of transmission and racial group. The only current effective treatment is combination therapy with pegylated interferon plus ribavirin (peg-IFNα + RBV) for 24–48 weeks based for genotypes 1 and 4 is 48 weeks, whereas the treatment for genotypes 2 and 3 is completed in 24 weeks. It has proved effective in up to 50% of those infected with HCV genotype 1 and 4 and it varies with other genotypes. HCV genotype is consider to be a clinically important parameter for determining both; the potential response and the duration of treatment.

Unveiling the interplay between NSAID-induced dysbiosis and autoimmune liver disease in children: insights into the hidden gateway to autism spectrum disorders. Evidence from ex vivo, in vivo, and clinical studies

Autism spectrum disorders (ASD) represent a diverse group of neuropsychiatric conditions, and recent evidence has suggested a connection between ASD and microbial dysbiosis. Immune and gastrointestinal dysfunction are associated with dysbiosis, and there are indications that modulating the microbiota could improve ASD-related behaviors. Additionally, recent findings highlighted the significant impact of microbiota on the development of autoimmune liver diseases, and the occurrence of autoimmune liver disease in children with ASD is noteworthy. In the present study, we conducted both an in vivo study and a clinical study to explore the relationship between indomethacin-induced dysbiosis, autoimmune hepatitis (AIH), and the development of ASD. Our results revealed that indomethacin administration induced intestinal dysbiosis and bacterial translocation, confirmed by microbiological analysis showing positive bacterial translocation in blood cultures. Furthermore, indomethacin administration led to disturbed intestinal permeability, evidenced by the activation of the NLRP3 inflammasomes pathway and elevation of downstream biomarkers (TLR4, IL18, caspase 1). The histological analysis supported these findings, showing widened intestinal tight junctions, decreased mucosal thickness, inflammatory cell infiltrates, and collagen deposition. Additionally, the disturbance of intestinal permeability was associated with immune activation in liver tissue and the development of AIH, as indicated by altered liver function, elevated ASMA and ANA in serum, and histological markers of autoimmune hepatitis. These results indicate that NSAID-induced intestinal dysbiosis and AIH are robust triggers for ASD existence. These findings were further confirmed by conducting a clinical study that involved children with ASD, autoimmune hepatitis (AIH), and a history of NSAID intake. Children exposed to NSAIDs in early life and complicated by dysbiosis and AIH exhibited elevated serum levels of NLRP3, IL18, liver enzymes, ASMA, ANA, JAK1, and IL6. Further, the correlation analysis demonstrated a positive relationship between the measured parameters and the severity of ASD. Our findings suggest a potential link between NSAIDs, dysbiosis-induced AIH, and the development of ASD. The identified markers hold promise as indicators for early diagnosis and prognosis of ASD. This research highlights the importance of maintaining healthy gut microbiota and supports the necessity for further investigation into the role of dysbiosis and AIH in the etiology of ASD.Peer Reviewe

Leveraging technology-driven strategies to untangle omics big data: circumventing roadblocks in clinical facets of oral cancer

Oral cancer is one of the 19most rapidly progressing cancers associated with significant mortality, owing to its extreme degree of invasiveness and aggressive inclination. The early occurrences of this cancer can be clinically deceiving leading to a poor overall survival rate. The primary concerns from a clinical perspective include delayed diagnosis, rapid disease progression, resistance to various chemotherapeutic regimens, and aggressive metastasis, which collectively pose a substantial threat to prognosis. Conventional clinical practices observed since antiquity no longer offer the best possible options to circumvent these roadblocks. The world of current cancer research has been revolutionized with the advent of state-of-the-art technology-driven strategies that offer a ray of hope in confronting said challenges by highlighting the crucial underlying molecular mechanisms and drivers. In recent years, bioinformatics and Machine Learning (ML) techniques have enhanced the possibility of early detection, evaluation of prognosis, and individualization of therapy. This review elaborates on the application of the aforesaid techniques in unraveling potential hints from omics big data to address the complexities existing in various clinical facets of oral cancer. The first section demonstrates the utilization of omics data and ML to disentangle the impediments related to diagnosis. This includes the application of technology-based strategies to optimize early detection, classification, and staging via uncovering biomarkers and molecular signatures. Furthermore, breakthrough concepts such as salivaomics-driven non-invasive biomarker discovery and omics-complemented surgical interventions are articulated in detail. In the following part, the identification of novel disease-specific targets alongside potential therapeutic agents to confront oral cancer via omics-based methodologies is presented. Additionally, a special emphasis is placed on drug resistance, precision medicine, and drug repurposing. In the final section, we discuss the research approaches oriented toward unveiling the prognostic biomarkers and constructing prediction models to capture the metastatic potential of the tumors. Overall, we intend to provide a bird’s eye view of the various omics, bioinformatics, and ML approaches currently being used in oral cancer research through relevant case studies

The involvement of antioxidant, stress, and immune-related genes in the responsive mechanisms of common carp (Cyprinus carpio) to hypersalinity exposure

Salinity stress is one of the marked influencing factors on the ecophysiology of aquaculture and is considered an important reason for the retreat of the fish industry. The current study is an endeavor to elucidate the molecular mechanisms that underlie the response to salinity stress in common carp. Fish (Average weight 5 ± 2 g) were randomly distributed into two groups; the 1st is a control was exposed to tap water (0.2 ppt salinity) and the 2nd is a treated was exposed to hypersalinity (10 ppt salinity) for five days. Serum biochemical indicators including total protein, albumin, globulins, A/G ratio, blood glucose, cortisone, Na+, K+, and Cl- levels were evaluated. Besides, Tumor necrosis factor-α, interleukin-1β, corticotropin-releasing hormone, and catalase enzyme mRNA expression levels were assessed in lymphoid and immunocompetent organs (liver and spleen) and osmoregulatory organs (kidney and gills) by using Real-time qPCR. Hypersalinity adversely affected the biochemical markers; total protein, albumin, and globulins decreased significantly; however, blood glucose, serum cortisol, and sodium markedly increased in fish exposed to hypersalinity compared with the control. In addition, from the molecular point of view, all the evaluated genes were upregulated at a high expression rate in the liver compared with other studied organs after the salinity challenge. On the contrary, hypersalinity modulated the expression of immune-related genes (Tumor necrosis factor-α and interleukin-1β) in the kidney and spleen and upregulated corticotropin-releasing hormone mRNA in all studied organs except gills. In conclusion, the obtained data clarified the molecular and biochemical mechanisms of salinity stress on the liver, kidney, spleen, and gills. Furthermore, it strongly suggests the implication of neural, endocrine, and immune systems in the responsive mechanisms to the salinity stress in carp

Unveiling the interplay between NSAID-induced dysbiosis and autoimmune liver disease in children: insights into the hidden gateway to autism spectrum disorders. Evidence from ex vivo, in vivo, and clinical studies

Autism spectrum disorders (ASD) represent a diverse group of neuropsychiatric conditions, and recent evidence has suggested a connection between ASD and microbial dysbiosis. Immune and gastrointestinal dysfunction are associated with dysbiosis, and there are indications that modulating the microbiota could improve ASD-related behaviors. Additionally, recent findings highlighted the significant impact of microbiota on the development of autoimmune liver diseases, and the occurrence of autoimmune liver disease in children with ASD is noteworthy. In the present study, we conducted both an in vivo study and a clinical study to explore the relationship between indomethacin-induced dysbiosis, autoimmune hepatitis (AIH), and the development of ASD. Our results revealed that indomethacin administration induced intestinal dysbiosis and bacterial translocation, confirmed by microbiological analysis showing positive bacterial translocation in blood cultures. Furthermore, indomethacin administration led to disturbed intestinal permeability, evidenced by the activation of the NLRP3 inflammasomes pathway and elevation of downstream biomarkers (TLR4, IL18, caspase 1). The histological analysis supported these findings, showing widened intestinal tight junctions, decreased mucosal thickness, inflammatory cell infiltrates, and collagen deposition. Additionally, the disturbance of intestinal permeability was associated with immune activation in liver tissue and the development of AIH, as indicated by altered liver function, elevated ASMA and ANA in serum, and histological markers of autoimmune hepatitis. These results indicate that NSAID-induced intestinal dysbiosis and AIH are robust triggers for ASD existence. These findings were further confirmed by conducting a clinical study that involved children with ASD, autoimmune hepatitis (AIH), and a history of NSAID intake. Children exposed to NSAIDs in early life and complicated by dysbiosis and AIH exhibited elevated serum levels of NLRP3, IL18, liver enzymes, ASMA, ANA, JAK1, and IL6. Further, the correlation analysis demonstrated a positive relationship between the measured parameters and the severity of ASD. Our findings suggest a potential link between NSAIDs, dysbiosis-induced AIH, and the development of ASD. The identified markers hold promise as indicators for early diagnosis and prognosis of ASD. This research highlights the importance of maintaining healthy gut microbiota and supports the necessity for further investigation into the role of dysbiosis and AIH in the etiology of ASD