Expression and activity of N-myristoyltransferase in lung inflammation of cattle and its role in neutrophil apoptosis

N-myristoyltransferase (NMT) attaches a 14 carbon fatty acid, myristic acid, to the N-terminal glycine residue of proteins. NMT exists in two isoforms NMT1 and NMT2. Myristoylated proteins play critical roles in protein–protein interactions, cell signaling and oncogenesis. Although elevated expression of NMT1 has been described in colorectal carcinoma, its expression and roles in normal and inflamed lungs of the cattle are unknown. Therefore, we investigated the expression and activity of NMT in a bovine model of lung inflammation induced with Mannheimia hemolytica and in vitro in neutrophils and macrophages. Western blots revealed increased expression of NMT1 in lungs from infected animals compared to control animals. Total NMT activity was reduced in inflamed lungs compared to control animals (p < 0.05) along with increased expression of enolase, a putative inhibitor of NMT. NMT1 staining was observed in the septum, vascular endothelium and the epithelium in the lungs from control as well as infected calves. NMT1 expression was intense in neutrophils in the necrotic areas in the inflamed lungs. Immuno-electron microscopy localized NMT1 in cytoplasm and nuclei of endothelium, pulmonary intravascular macrophages and airway epithelium. Total NMT activity and NMT1 expression were increased in neutrophils and macrophages exposed to Escherichia coli LPS in vitro. NMT knockdown increased apoptosis in activated neutrophils. This is the first report demonstrating expression of NMT in normal and inflamed lungs and a novel role for NMT in regulation of neutrophil lifespan

A cluster-randomised trial comparing home-based primary health care and usual clinic care for epilepsy in a resource-limited country

OBJECTIVE: To ascertain whether home-based care with community and primary healthcare workers' support improves adherence to antiseizure medications, seizure control, and quality of life over routine clinic-based care in community samples of people with epilepsy in a resource-poor country. METHODS: Participants included consenting individuals with active epilepsy identified in a population survey in impoverished communities. The intervention included antiseizure medication provision, adherence reinforcement and epilepsy self- and stigma management guidance provided by a primary health care-equivalent worker. We compared the intervention group to a routine clinic-based care group in a cluster-randomised trial lasting 24 months. The primary outcome was antiseizure medication adherence, appraised from monthly pill counts. Seizure outcomes were assessed by monthly seizure aggregates and time to first seizure and impact by the Personal Impact of Epilepsy scale. RESULTS: Enrollment began on 25.09.2017 and was complete by 24.07.2018. Twenty-four clusters, each comprising ten people with epilepsy, were randomised to either home- or clinic-care. Home-care recepients were more likely to have used up their monthly-dispensed epilepsy medicine stock (Regression Coefficient: 0.585; 95% Confidence Intervals, 0.289 to 0.881; P=0.001) and had fewer seizures (Regression coefficient: -2.060; 95%CI, -3.335 to -0.785; P=0.002). More people from clinic-care (n=44; 37%) than home-care (n=23; 19%) exited the trial (P=0.003). The time to first seizure, adverse effects and the personal impact of epilepsy were similar in the two arms. SIGNIFICANCE: Home care for epilepsy compared to clinic care in resource-limited communities improves medication adherence and seizure outcomes and reduces the secondary epilepsy treatment gap

Triethyl­ammonium N′-(benzyl­sulfanylthio­carbonyl)-2-hydroxy­benzohydrazidate

In the title compound, C6H16N+·C15H13N2O2S2 −, the thione S atom is in a cis configuration with respect to the phenyl and benzene rings, while it adopts a trans configuration with respect to the carbonyl group. The dihedral angle between the benzene and phenyl rings is 78.81 (2)°. The mol­ecular conformation is stabilized by intra­molecular O—H⋯O and N—H⋯S hydrogen bonds, while inter­molecular N—H⋯O, N—H⋯N and weak C—H⋯O inter­actions help to stabilize the crystal structure

The transition between stochastic and deterministic behavior in an excitable gene circuit

We explore the connection between a stochastic simulation model and an ordinary differential equations (ODEs) model of the dynamics of an excitable gene circuit that exhibits noise-induced oscillations. Near a bifurcation point in the ODE model, the stochastic simulation model yields behavior dramatically different from that predicted by the ODE model. We analyze how that behavior depends on the gene copy number and find very slow convergence to the large number limit near the bifurcation point. The implications for understanding the dynamics of gene circuits and other birth-death dynamical systems with small numbers of constituents are discussed.Comment: PLoS ONE: Research Article, published 11 Apr 201

Tuberculosis Intestinal y Enfermedad de Crohn. Lo difícil del diagnóstico diferencial

La tuberculosis (TB) es la infección más prevalente del mundo y afecta a un tercio de la población mundial, predominantemente a países subdesarrollados, representando la TB intestinal la sexta causa en frecuencia de afectación tuberculosa extrapulmonar. La enfermedad de Crohn (EC) es una enfermedad inflamatoria crónica intestinal que surge de la interacción de factores inmunológicos, ambientales y genéticos. El diagnóstico diferencial entre TB intestinal y EC puede resultar un reto, sobre todo en pacientes inmunodeprimidos y en aquellos procedentes de áreas endémicas de TB, debido a los cambios en la epidemiología de ambas patologías

Peeling and aspiration of elschnig pearls! An effective alternative to Nd:YAG laser capsulotomy!

To evaluate the efficacy of peeling and aspiration of Elschnig pearls. Retrospective study in a medical college hospital. Records of 217 eyes which underwent surgical peeling and aspiration for membranous PCO between 2006 and 2009, was reviewed. Peeling and aspiration was fashioned with a blunt tipped 20G cannula after stabilizing anterior chamber with anterior chamber maintainer. Post-operative vision and complications were analyzed. Mc Nemar and Chi square tests. The mean age was 56.84 years. 85.71% patients achieved best corrected visual acuity (BCVA) of 20/20 at 3 m. Recurrence of pearls, uveitis and cystoid macular edema were the most common causes of reduced vision. Peeling and aspiration of pearls seem to be a viable alternative to Neodymium yttrium garner aluminium (Nd: YAG) laser capsulotomy for membranous PCO

N-myristoyltransferase: A potential novel diagnostic marker for colon cancer

Abstract Background Colon cancer is the second leading cause of cancer deaths in the western world. If detected early, colorectal cancer is one of the most treatable forms of cancer. Unfortunately, very few people are screened. N-myristoyltransferase (NMT) catalyzes myristoylation of various proteins including oncoproteins. We have demonstrated earlier the alteration of NMT activity during the progression of colorectal cancer and established NMT as a putative therapeutic target for cancer. Methods Peripheral blood samples and bone marrow were collected from the colon cancer patients and azoxymethane induced colonic tumor rats and their controls respectively. NMT activity and expression was determined as reported earlier. Immunohistochemical studies were carried out using standard procedures. Results In this study we demonstrate for the first time altered expression and localization of NMT in the peripheral blood and bone marrow in colon cancer patients. Immunohistochemical analysis revealed weak to negative staining for NMT in peripheral blood mononuclear cells (PBMC) of controls, whereas strong positivity was observed in PBMC colon cancer patients. In addition, we observed that NMT was localized mostly in the nuclei of the bone marrow (BM) mononuclear cells of the colon cancer patients, whereas NMT remained cytoplasmic in the control bone marrow specimens. Conclusion The strikingly different NMT expression offers the basis of a potential adjunct investigative tool for screening or diagnosis of patients at risk for or suspected of having colon cancer. Furthermore, altered localization of NMT in BM of tumor bearing hosts may serve as an added investigative tool for the diagnostic purpose.</p

Safety and efficacy of personalized versus standard initial dosing of thiopurines: Systematic review and meta-analysis of randomized trials

Pretherapy assessment of specific genetic polymorphism (TPMT, NUDT15, FTO, RUNX1, etc) or enzyme levels (for TPMT) may help personalize the dose of thiopurines and avoid adverse effects. A systematic review of randomized controlled trials (RCTs) comparing personalized versus standard strategy for initial thiopurine dosing was performed. The electronic databases were searched on 27 September 2022. The outcomes were overall adverse effects, myelotoxicity, drug interruptions, and therapeutic efficacy with either strategy. The certainty of evidence was assessed using GRADE methodology. We included six randomized trials, done dominantly in patients with inflammatory bowel disease (IBD). The personalized strategies were genotype testing in 4 trials (TPMT in three trials, NUDT15 in two) and enzyme levels for TPMT in two trials. The pooled risk of myelotoxicity in personalized dosing was lower [RR = 0.72 (95%CI, 0.55–0.94, I2 = 0%)]. The pooled risk of pancreatitis (RR = 1.10I, 0.78–1.56, I2 = 0%), hepatotoxicity (RR = 1.13, 0.69–1.88, I2 = 45), and GI intolerance (RR = 1.01, 0.92–1.10, I2 = 0) were similar in two groups. The pooled risk of drug interruption in individualized dosing was similar to the standard dosing group (RR = 0.97, I2 = 68%). Personalized testing-based initial thiopurine dosing is protective against myelotoxicity as compared to standard weight-based dosing.</p