Clinical Observations IN INDIA DURING THE WAR.

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Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection.

Hospital infection control measures are crucial to tuberculosis (TB) control strategies within settings caring for human immunodeficiency virus (HIV)-positive patients, as these patients are at heightened risk of developing TB. Pyrazinamide (PZA) is a potent drug that effectively sterilizes persistent Mycobacterium tuberculosis bacilli. However, PZA resistance associated with mutations in the nicotinamidase/pyrazinamidase coding gene, pncA, is increasing. A total of 794 patient isolates obtained from four sites in Lima, Peru, underwent spoligotyping and drug resistance testing. In one of these sites, the HIV unit of Hospital Dos de Mayo (HDM), an isolation ward for HIV/TB coinfected patients opened during the study as an infection control intervention: circulating genotypes and drug resistance pre- and postintervention were compared. All other sites cared for HIV-negative outpatients: genotypes and drug resistance rates from these sites were compared with those from HDM. HDM patients showed high concordance between multidrug resistance, PZA resistance according to the Wayne method, the two most common genotypes (spoligotype international type [SIT] 42 of the Latino American-Mediterranean (LAM)-9 clade and SIT 53 of the T1 clade), and the two most common pncA mutations (G145A and A403C). These associations were absent among community isolates. The infection control intervention was associated with 58-92% reductions in TB caused by SIT 42 or SIT 53 genotypes (odds ratio [OR] = 0.420, P = 0.003); multidrug-resistant TB (OR = 0.349, P < 0.001); and PZA-resistant TB (OR = 0.076, P < 0.001). In conclusion, pncA mutation typing, with resistance testing and spoligotyping, was useful in identifying a nosocomial TB outbreak and demonstrating its resolution after implementation of infection control measures

Larger portions make me eat more : awareness of the external factors that influence food intake

There is consistent evidence that the amount of food people consume can be influenced by external factors, such as food portion size or the amount of food others are eating. However research studies to date have suggested that people are generally unaware of the influence that these external factors have on food intake. In the present research we directly tested whether consumers are aware of how external factors can affect their food intake. In Study 1 we re-analysed data from a study in which an effect of portion size on food intake was observed and post-consumption, participants were asked whether they believed portion size had influenced their food intake. In Study 2 participants were asked to indicate whether several different external factors known to increase food intake would be likely to increase, decrease or have no effect on how much they would eat in hypothetical scenarios. In Study 1, a large proportion of participants (56%) believed that their food intake was influenced by portion size. In Study 2, a large proportion of participants accurately identified that external factors known to affect eating behaviour would be likely to increase their food intake: portion size (73%), social influence (40%), food variety (75%), and distraction (59%). Together these results suggest that consumers show awareness of the influence that external factors have on their food intake

On traces for H(curl,Ω) in Lipschitz domains

AbstractWe study tangential vector fields on the boundary of a bounded Lipschitz domain Ω in R3. Our attention is focused on the definition of suitable Hilbert spaces corresponding to fractional Sobolev regularities and also on the construction of tangential differential operators on the non-smooth manifold. The theory is applied to the characterization of tangential traces for the space H(curl,Ω). Hodge decompositions are provided for the corresponding trace spaces, and an integration by parts formula is proved

The mechanisms of melatonin action in shielding photosynthesis during heat stress

The escalating global climate shifts lead to several negative impacts, including a continuous increase in average temperatures, imposing significant consequences on plant physiology, biochemical dynamics, and molecular processes. Central to these ramifications is the process of photosynthesis, pivotal for carbohydrate synthesis and essential for sustaining growth amidst normal or stressful environmental conditions. Exposure to heat stress (HS) negatively affects the photosynthetic potential, primarily due to the increased synthesis of reactive oxygen species, disrupting the optimal functionality of the photosynthetic apparatus. Melatonin (MLT) has emerged as a multifaceted signaling molecule exhibiting promising capabilities in mitigating the adverse effects of abiotic stress including HS on plants. While a substantial body of literature addresses the enhancement of plant resilience to various environmental stresses using MLT, the present review specifically focuses on the impact of MLT on photosynthesis during HS. It emphasizes MLT’s role in regulating chlorophyll synthesis and degradation, regulating stomatal movement, safeguarding photosynthetic proteins, and sustaining the photosynthetic process under HS. This could be achieved by various mechanisms including enhancing the transcription of photosystem genes, activating antioxidant defenses, promoting the xanthophyll cycle, and modulating enzymes involved in photosynthesis and carbohydrate metabolism. Consequently, this review aims to enhance our understanding of how MLT mediates the protection of the photosynthesis process under HS, offering insights for the development of heat-tolerant crops

Metallochaperones Are Needed for Mycobacterium tuberculosis and Escherichia coli Nicotinamidase-Pyrazinamidase Activity.

Mycobacterium tuberculosis nicotinamidase-pyrazinamidase (PZAse) is a metalloenzyme that catalyzes conversion of nicotinamide-pyrazinamide to nicotinic acid-pyrazinoic acid. This study investigated whether a metallochaperone is required for optimal PZAse activity. M. tuberculosis and Escherichia coli PZAses (PZAse-MT and PZAse-EC, respectively) were inactivated by metal depletion (giving PZAse-MT-Apo and PZAse-EC-Apo). Reactivation with the E. coli metallochaperone ZnuA or Rv2059 (the M. tuberculosis analog) was measured. This was repeated following proteolytic and thermal treatment of ZnuA and Rv2059. The CDC1551 M. tuberculosis reference strain had the Rv2059 coding gene knocked out, and PZA susceptibility and the pyrazinoic acid (POA) efflux rate were measured. ZnuA (200 μM) achieved 65% PZAse-EC-Apo reactivation. Rv2059 (1 μM) and ZnuA (1 μM) achieved 69% and 34.3% PZAse-MT-Apo reactivation, respectively. Proteolytic treatment of ZnuA and Rv2059 and application of three (but not one) thermal shocks to ZnuA significantly reduced the capacity to reactivate PZAse-MT-Apo. An M. tuberculosis Rv2059 knockout strain was Wayne positive and susceptible to PZA and did not have a significantly different POA efflux rate than the reference strain, although a trend toward a lower efflux rate was observed after knockout. The metallochaperone Rv2059 restored the activity of metal-depleted PZAse in vitro Although Rv2059 is important in vitro, it seems to have a smaller effect on PZA susceptibility in vivo. It may be important to mechanisms of action and resistance to pyrazinamide in M. tuberculosis Further studies are needed for confirmation.IMPORTANCE Tuberculosis is an infectious disease caused by the bacterium Mycobacterium tuberculosis and remains one of the major causes of disease and death worldwide. Pyrazinamide is a key drug used in the treatment of tuberculosis, yet its mechanism of action is not fully understood, and testing strains of M. tuberculosis for pyrazinamide resistance is not easy with the tools that are presently available. The significance of the present research is that a metallochaperone-like protein may be crucial to pyrazinamide's mechanisms of action and of resistance. This may support the development of improved tools to detect pyrazinamide resistance, which would have significant implications for the clinical management of patients with tuberculosis: drug regimens that are appropriately tailored to the resistance profile of a patient's individual strain lead to better clinical outcomes, reduced onward transmission of infection, and reduction of the development of resistant strains that are more challenging and expensive to treat

Vertical flow in the Southern Ocean estimated from individual moorings

In this study, we demonstrate that oceanic vertical velocities can be estimated from individual mooring measurements, even for non-stationary flow. This result is obtained under three assumptions: i. weak diffusion (Péclet number ≫1), ii. weak friction (Reynolds number ≫1), and iii. small inertial terms (Rossby number ≪1). The theoretical framework is applied to a set of 4 moorings located in the Southern Ocean. For this site, the diagnosed vertical velocities are highly variable in time, their standard deviation being one-to-two orders of magnitude greater than their mean. We demonstrate that the time-averaged vertical velocities are largely induced by geostrophic flow, and can be estimated from the time-averaged density and horizontal velocities. This suggests that local time-mean vertical velocities are primarily forced by the time-mean ocean dynamics, rather than by e.g. transient eddies or internal waves. We also show that, in the context of these four moorings, the time-mean vertical flow is consistent with stratified Taylor column dynamics in the presence of a topographic obstacle

Antioxidant Therapy Does Not Reduce Pain in Patients with Chronic Pancreatitis: The ANTICIPATE Study

Background & Aims: We investigated whether antioxidant therapy reduces pain and improves quality of life in patients with chronic pancreatitis. Methods: We performed a double-blind, randomized, controlled trial that compared the effects of antioxidant therapy with placebo in 70 patients with chronic pancreatitis. Patients provided 1 month of baseline data and were followed up for 6 months while receiving either Antox version 1.2 (Pharma Nord, Morpeth, UK) or matched placebo (2 tablets, 3 times/d). The primary analysis was baseline-adjusted change in pain score at 6 months, assessed by an 11-point numeric rating scale. Secondary analyses included alternative analyses of clinic and diary pain scores, scores on quality-of-life tests (the EORTC-QLQ-C30, QLQ-PAN28, EuroQOL EQ-5D, and EQ visual analog score), levels of antioxidants, use of opiates, and adverse events. Analyses, reported by intention to treat, were prospectively protocol-defined. Results: After 6 months, pain scores reported to the clinic were reduced by 1.97 from baseline in the placebo group and by 2.33 in the antioxidant group but were similar between groups (−0.36; 95% confidence interval, −1.44 to 0.72; P = .509). Average daily pain scores from diaries were also similar (3.05 for the placebo group, 2.93 for the antioxidant group, a difference of 0.11; 95% confidence interval, 1.05–0.82; P = .808). Measures of quality of life were similar between groups, as was opiate use and number of hospital admissions and outpatient visits. Blood levels of vitamin C and E, β-carotene, and selenium were increased significantly in the antioxidant group. Conclusi1ons: In patients with painful chronic pancreatitis of predominantly alcoholic origin, antioxidant therapy did not reduce pain or improve quality of life, despite causing a sustained increase in blood levels of antioxidants. Trial registration: ISRCTN-21047731

Appraisal of the Role of Gaseous Signaling Molecules in Thermo-Tolerance Mechanisms in Plants

: A significant threat to the ongoing rise in temperature caused by global warming. Plants have many stress-resistance mechanisms, which is responsible for maintaining plant homeostasis. Abiotic stresses largely increase gaseous molecules' synthesis in plants. The study of gaseous signaling molecules has gained attention in recent years. The role of gaseous molecules, such as nitric oxide (NO), hydrogen sulfide (H2S), carbon dioxide (CO2), carbon monoxide (CO), methane (CH4), and ethylene, in plants under temperature high-temperature stress are discussed in the current review. Recent studies revealed the critical function that gaseous molecules play in controlling plant growth and development and their ability to respond to various abiotic stresses. Here, we provide a thorough overview of current advancements that prevent heat stress-related plant damage via gaseous molecules. We also explored and discussed the interaction of gaseous molecules. In addition, we provided an overview of the role played by gaseous molecules in high-temperature stress responses, along with a discussion of the knowledge gaps and how this may affect the development of high-temperature-resistant plant species