Barley MLA3 recognizes the host-specificity effector Pwl2 from Magnaporthe oryzae.

Plant nucleotide-binding leucine-rich repeat (NLRs) immune receptors directly or indirectly recognize pathogen-secreted effector molecules to initiate plant defense. Recognition of multiple pathogens by a single NLR is rare and usually occurs via monitoring for changes to host proteins; few characterized NLRs have been shown to recognize multiple effectors. The barley (Hordeum vulgare) NLR gene Mildew locus a (Mla) has undergone functional diversification, and the proteins encoded by different Mla alleles recognize host-adapted isolates of barley powdery mildew (Blumeria graminis f. sp. hordei [Bgh]). Here, we show that Mla3 also confers resistance to the rice blast fungus Magnaporthe oryzae in a dosage-dependent manner. Using a forward genetic screen, we discovered that the recognized effector from M. oryzae is Pathogenicity toward Weeping Lovegrass 2 (Pwl2), a host range determinant factor that prevents M. oryzae from infecting weeping lovegrass (Eragrostis curvula). Mla3 has therefore convergently evolved the capacity to recognize effectors from diverse pathogens.

Tofacitinib in Acute Severe Ulcerative Colitis (TACOS): A Randomized Controlled Trial.

INTRODUCTION: Intravenous corticosteroids are the mainstay of treatment of patients hospitalized with acute severe ulcerative colitis (ASUC). However, 30%-40% of the patients are refractory to corticosteroids. We investigated whether addition of tofacitinib to corticosteroids improved the treatment responsiveness in patients with ASUC. METHODS: This single-center, double-blind, placebo-controlled trial randomized adult patients with ASUC (defined by the Truelove Witts severity criteria) to receive either tofacitinib (10 mg thrice daily) or a matching placebo for 7 days while continuing intravenous corticosteroids (hydrocortisone 100 mg every 6 hours). The primary end point was response to treatment (decline in the Lichtiger index by >3 points and an absolute score <10 for 2 consecutive days without the need for rescue therapy) by day 7. The key secondary outcome was the cumulative probability of requiring initiation of infliximab or undergoing colectomy within 90 days following randomization. All analyses were performed in the intention-to-treat population. RESULTS: A total of 104 patients were randomly assigned to a treatment group (53 to tofacitinib and 51 to placebo). At day 7, response to treatment was achieved in 44/53 (83.01%) patients receiving tofacitinib vs 30/51 (58.82%) patients receiving placebo (odds ratio 3.42, 95% confidence interval 1.37-8.48, P = 0.007). The need for rescue therapy by day 7 was lower in the tofacitinib arm (odds ratio 0.27, 95% confidence interval 0.09-0.78, P = 0.01). The cumulative probability of need for rescue therapy at day 90 was 0.13 in patients who received tofacitinib vs 0.38 in patients receiving placebo (log-rank P = 0.003). Most of the treatment-related adverse effects were mild. One patient, receiving tofacitinib, developed dural venous sinus thrombosis. DISCUSSION: In patients with ASUC, combination of tofacitinib and corticosteroids improved treatment responsiveness and decreased the need for rescue therapy.

Analysis and Prediction of COVID-19 Multivariate Data Using Deep Ensemble Learning Methods.

The global economy has suffered losses as a result of the COVID-19 epidemic. Accurate and effective predictive models are necessary for the governance and readiness of the healthcare system and its resources and, ultimately, for the prevention of the spread of illness. The primary objective of the project is to build a robust, universal method for predicting COVID-19-positive cases. Collaborators will benefit from this while developing and revising their pandemic response plans. For accurate prediction of the spread of COVID-19, the research recommends an adaptive gradient LSTM model (AGLSTM) using multivariate time series data. RNN, LSTM, LASSO regression, Ada-Boost, Light Gradient Boosting and KNN models are also used in the research, which accurately and reliably predict the course of this unpleasant disease. The proposed technique is evaluated under two different experimental conditions. The former uses case studies from India to validate the methodology, while the latter uses data fusion and transfer-learning techniques to reuse data and models to predict the onset of COVID-19. The model extracts important advanced features that influence the COVID-19 cases using a convolutional neural network and predicts the cases using adaptive LSTM after CNN processes the data. The experiment results show that the output of AGLSTM outperforms with an accuracy of 99.81% and requires only a short time for training and prediction.

Performance analysis of multiple-beam WDM free space laser-communication system using homodyne detection approach.

A free space optical module is used in laser communication to transport a signal from the transmitter to the receiver. Free Space Optical Communication (FSOC) is a Line of Sight connectivity that sends a highly narrow beamwidth. FSOC provides high bandwidth and data rates greater than 10 Gbps. Although FSOC technology has several advantages, it is inefficient for long-distance transmission because of many constraints caused by atmospheric variables. In FSOC connections, turbulence-induced scintillation is a severe problem that significantly reduces link performance. Keeping this problem in mind, the objective of this study is to enhance FSOC performance in terms of energy efficiency, spectral efficiency and long-distance transmission. To achieve this, a study is employed using a hybrid combination of Higher-order Gaussian filter (HGF), post-amplification and a homodyne detection method. Precisely, the simulative study of 32-channel wavelength division multiplexing (WDM) FSOC has used channel model Gamma-Gamma with single-beam (SB), dual-beam (DB), four multiple-beam (MB4) and eight multiple-beam (MB8) techniques. The proposed framework has achieved a Channel capacity of more than 320 Gbps. The transmission range enhancement of 112% and reduction in transmitted power of 100% are achieved, which are considerably more significant compared with state-of-the-art literature studies. The OptiSystem platform is used to gather the outcomes. The performance is based on parametric analysis of bit error rate (BER), Quality (Q) factor and eye height.

Inflammatory bowel disease (IBD)-disk accurately predicts the daily life burden and parallels disease activity in patients with IBD.

BACKGROUND/AIMS: The inflammatory bowel disease (IBD)-disk is a validated, visual, 10-item, self-administered questionnaire used to evaluate IBD-related disability. The present study aimed to evaluate IBD-disk in assessment of IBD daily life burden and its relation with disease activity. METHODS: A cross-sectional study was conducted between June 2021 and December 2021. Patients with IBD were asked to complete the IBD-disk and a visual analogue scale of IBD daily-life burden (scored from 0-10, score >5 indicative of high burden). The internal consistency of IBD-disk, correlation with IBD daily life burden and disease activity (assessed by partial Mayo score and Harvey Bradshaw Index in patients with ulcerative colitis [UC] and Crohn's disease [CD], respectively) and diagnostic performance of IBD-disk to detect high burden were analyzed. RESULTS: Out of the 546 patients (mean age 40.33±13.74 years, 282 [51.6%] males) who completed the IBD-disk, 464 (84.98%) had UC and the remaining (n=82, 15.02%) had CD. A total of 311 patients (291 UC and 20 CD; 56.95%) had active disease. The mean IBD-disk total score and IBD daily life burden were 18.39±15.23 and 2.45±2.02, respectively. The IBD-disk total score correlated strongly with the IBD daily life burden (ρ=0.94, P<0.001), moderately with partial Mayo score (ρ=0.50) and weakly with Harvey Bradshaw Index (ρ=0.34). The IBD-disk total score >30 predicted high IBD daily-life burden. CONCLUSIONS: The IBD-disk accurately predicts the daily life burden and parallels disease activity in patients with IBD and can be applied in clinical practice. (Intest Res, Published online).

Clinical spectrum of elderly-onset inflammatory bowel disease in India.

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) is increasingly being recognized in elderly patients. Data on clinical spectrum of elderly-onset IBD patients is lacking from India. METHODS: A cross-sectional retrospective analysis of a prospectively maintained database of patients diagnosed with IBD was conducted at 2 centers in India. The clinical spectrum of elderly-onset IBD including demographic profile (age and sex), clinical presentation, disease characteristics (disease behavior and severity, extent of disease), and treatment were recorded and compared with adult-onset IBD. RESULTS: During the study period, 3,922 (3,172 ulcerative colitis [UC] and 750 Crohn's disease [CD]) patients with IBD were recorded in the database. A total of 186 patients (4.74%; 116 males [62.36%]) had elderly-onset IBD (69.35% UC and 30.64% CD). Diarrhea, blood in stools, nocturnal frequency and pain abdomen were the commonest presentations for UC, whereas pain abdomen, weight loss and diarrhea were the most frequent symptoms in CD. For both elderly onset UC and CD, majority of the patients had moderately severe disease. Left-sided colitis was the commonest disease location in UC. Isolated ileal disease and inflammatory behavior were the most common disease location and behavior, respectively in CD. 5-Aminosalicylates were the commonest prescribed drug for both elderly onset UC and CD. Thiopurines and biologics were used infrequently. Prevalence of colorectal cancer was higher in elderly onset IBD. CONCLUSIONS: Elderly onset IBD is not uncommon in India. Both the elderly onset UC and CD were milder, with no significant differences in disease characteristics (disease extent, location and behavior) when compared to adult-onset IBD. Colorectal cancer was more common in elderly onset IBD.

International Multicentre Study of Candida auris Infections.

Background:Candida auris has emerged globally as a multi-drug resistant yeast and is commonly associated with nosocomial outbreaks in ICUs. Methods: We conducted a retrospective observational multicentre study to determine the epidemiology of C. auris infections, its management strategies, patient outcomes, and infection prevention and control practices across 10 centres from five countries. Results: Significant risk factors for C. auris infection include the age group of 61-70 years (39%), recent history of ICU admission (63%), diabetes (63%), renal failure (52%), presence of CVC (91%) and previous history of antibiotic treatment (96%). C. auris was commonly isolated from blood (76%). Echinocandins were the most sensitive drugs. Most common antifungals used for treatment were caspofungin (40%), anidulafungin (28%) and micafungin (15%). The median duration of treatment was 20 days. Source removal was conductedin 74% patients. All-cause crude mortality rate after 30 days was 37%. Antifungal therapy was associated with a reduction in mortality (OR:0.27) and so was source removal (OR:0.74). Contact isolation precautions were followed in 87% patients. Conclusions:C. auris infection carries a high risk for associated mortality. The organism is mainly resistant to most azoles and even amphotericin-B. Targeted antifungal therapy, mainly an echinocandin, and source control are the prominent therapeutic approaches.

Exclusive enteral nutrition for induction of remission in anti-tumor necrosis factor refractory adult Crohn's disease: the Indian experience.

BACKGROUND/AIMS: Exclusive enteral nutrition (EEN) is recommended for induction of remission in pediatric Crohn's disease (CD). However, it is not currently recommended for inducing remission in adults. This report describes the use of 12-week EEN for induction of remission in anti-tumor necrosis factor (anti-TNF) refractory adult CD. METHODS: This is a retrospective analysis of adults with moderate to severe active (Crohn's Disease Activity Index [CDAI] >220) anti-TNF refractory CD, who received EEN for 12 weeks between April 2018 and March 2019 at Dayanand Medical College and Hospital, Ludhiana, India. Primary outcomes included achievement of clinical remission and fistula healing at 12 weeks. Improvement in inflammatory markers and nutritional status were the secondary end points. RESULTS: Out of 23 patients who received anti-TNF agents, 7 (30.4%) were refractory and were offered EEN as a salvage therapy. Six patients (66.7% females, mean age 25.6±6.5 years) consented. Four patients (66.6%) achieved clinical remission (CDAI <150). Mean CDAI of patients decreased significantly after 12 weeks of EEN (388.8±74.8 vs. 160.0±25.2, P<0.001). Perianal fistulas showed clinical response (drainage decreased by >50%), though none achieved remission. Entero-enteric fistulae showed complete healing. Mean body mass index improved from 15.6±3.1 to 18.9±1.9 kg/m2 at week 12 (P=0.003). Hemoglobin and serum albumin also improved from 8.2±1.1 g/dL and 2.8±0.3 g/dL at baseline to 12.6±0.6 g/dL and 3.6±0.5 g/dL post-EEN respectively (P<0.001 and P=0.006 respectively). CONCLUSIONS: EEN appears to be an effective and well tolerated therapy for induction of remission in anti-TNF refractory adult CD. More data from prospective trials with larger number of patients is required.

Acceptability, tolerability, and safety of fecal microbiota transplantation in patients with active ulcerative colitis (AT&S Study).

BACKGROUND AND AIM: Fecal microbiota transplantation (FMT) targets gut microbiome dysbiosis and is an emerging therapy for ulcerative colitis (UC). Although initial results with FMT in patients with active UC are encouraging, data regarding its acceptability, tolerability, and safety are scant. METHODS: A retrospective analysis of patients with active UC (Mayo clinic score ≥ 4), who received multisession FMT (at weeks 0, 2, 6, 10, 14, 18, and 22) via colonoscopy between June 2016 and June 2018, was performed. Patient acceptability, tolerability, and immediate and long-term safety of the therapy were assessed. RESULTS: Of the 129 patients with active UC who were offered FMT, 101 patients consented, giving acceptability of 78.3%. Fecal slurry retention time improved with each session (3.27 ± 1.06 h for the first session vs 5.12 ± 0.5 h for the seventh session). Abdominal discomfort, flatulence, abdominal distension, borborygmi, and low-grade fever (30.8%, 15.9%, 9.8%, 7.9%, and 7.6%, respectively) were the most common post-procedural short-term adverse events. Long-term adverse events included new-onset urticaria (n = 2, 4.3%), arthritis/arthralgia (n = 3, 6.5%), depression (n = 1, 2.2%), partial sensorineural hearing loss (n = 1, 2.2%), and allergic bronchitis (n = 1, 2.2%). Thirteen (12.9%) patients dropped out because of adverse events. CONCLUSION: Fecal microbiota transplantation appears to be a safe and well-tolerated procedure, with good acceptability in patients with active UC.

Effect of pretreatment regimens of 1-aminobenzotriazole on metabolism and gastric emptying of probe compounds in rat.

1-Aminobenzotriazole (ABT) is a mechanism-based inactivator of major cytochrome P450 (CYP) enzymes, which is used in multiple mechanistic studies. The purpose was to evaluate the effect of 2 and 16-h pretreatment regimens of ABT on the exposures of triazolam in rat. Another objective was to evaluate the effect of ABT on gastric emptying of acetaminophen. Plasma area under the curve (AUC) of triazolam was increased by 101-fold and 81-fold for the rats pretreated with ABT at 2 and 16 h, respectively, compared to control rats. Time to reach maximum concentration was 0.3, 4.8 and 3.7 h in control, 2 and 16-h pretreatment animals, respectively. In the case of acetaminophen, where Tmax was not delayed, the mean absorption time (MAT) in control, 2 and 16 h ABT pretreatment groups were 0.3, 4.6 and 2.9 h, respectively, suggesting delayed absorption. This hypothesis was further supported by GastroPlusTM simulation. In summary, extent of triazolam absorption was increased to a similar extent with both 2 and 16 h ABT pretreatment regimens, suggesting that either of the regimen can be used to increase parent exposures in rat. With ABT pretreatment, delayed absorption of triazolam and acetaminophen was observed, as suggested by delay in Tmax and MAT, respectively.

A comparative study of various topical nonsteroidal anti-inflammatory drugs to steroid drops for control of post cataract surgery inflammation.

BACKGROUND: Postoperative inflammation continues to be a cause of patient discomfort, delayed recovery, and in some cases, suboptimal visual results. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) and steroid are commonly used in the management and prevention of noninfectious ocular inflammation following cataract surgery. AIMS: The aim was to study the safety and efficacy of various NSAIDs drops for control of postoperative inflammation following cataract surgery and compare with steroid eye drops in a patient following cataract surgery. SUBJECTS AND METHODS: Totally, 200 patients undergoing phacoemulsification with posterior chamber intraocular lens implantation were randomly assigned to receive either nepafenac 0.1% 3 times daily, bromfenac 0.09% twice daily, ketorolac 0.5% 4 times daily for 1 month or 1% prednisolone eye drops as their postoperative anti-inflammatory medication with 50 cases in each group. The patients were examined at the 1st day (baseline), 1st week, 2nd week, and 4th week after surgery. Postoperative inflammation was evaluated subjectively by intraocular pressure, slit-lamp assessment of signs of inflammation, including conjunctival hyperemia, ocular pain, and aqueous cells and flare. STATISTICAL ANALYSIS: Statistical analysis was performed by the SPSS program for Windows, version 17.0. RESULTS AND CONCLUSIONS: In our study, we found that prednisolone 1% was more effective in controlling postoperative intraocular inflammation in terms of reducing anterior chamber cells and flare. We found that ketorolac 0.5% and nepafenac 0.1% were equally effective in controlling postoperative ocular pain and inflammation. All four drugs are effective in controlling post cataract surgery ocular inflammation. Intraocular inflammation is best controlled with prednisolone 1%, while ocular pain and hyperemia are better controlled with NSAIDs in the early postoperative periods.

Case report on an infant presenting with hypoglycemia, and milky serum.

A 4-month-old male baby who presented in a moribund condition with seizures was found to have hepatomegaly, hypoglycemia and milky serum. Serum triglycerides were markedly elevated (3 168 mg/dL) with cholesterol being 257 mg/dL and high density lipoprotein levels were low (19 mg/dL). The possibility of glycogen storage disease type I was considered in the diagnosis. Infants with glycogen storage disease type I may present like sepsis. The association of hepatomegaly, hypoglycemia and abnormal lipid profile stated above should alert the physician to consider glycogen storage disease type I in the diagnosis.

Paramagnetism-based refinement strategy for the solution structure of human alpha-parvalbumin.

In the frame of a research aimed at the detailed structural characterization of human calcium-binding proteins of the EF-hand family, the solution structure of human alpha-parvalbumin has been solved by NMR and refined with the help of substitution of the Ca(2+) ion in the EF site with the paramagnetic Dy(3+) ion. A simple (1)H-(15)N HSQC spectrum allowed the NH assignments based on the properties of Dy(3+). This allowed us to exploit pseudocontact shifts and residual dipolar couplings for solution structure refinement. The backbone and heavy atom RMSD are 0.55 +/- 0.08 and 1.02 +/- 0.08 A, respectively, and decrease to 0.39 +/- 0.05 and 0.90 +/- 0.06 A upon refinement with paramagnetism-based restraints. The RMSD for the metal itself in the EF site in the refined structure is 0.26 +/- 0.12 A. Backbone NH R(1), R(2), and NOE measured at two temperatures show the protein to be relatively rigid. The NH orientations are well determined by the paramagnetism-based restraints. This allows us to detect small but significant local structural differences with the orthologue protein from rat, whose X-ray structure is available at 2.0 A resolution. All differences are related to local changes in the amino acidic composition.