Rapid symptom control in neuroleptic malignant syndrome with electroconvulsive therapy: A case report

Introduction: Neuroleptic malignant syndrome (NMS), thought to arise through dopamine antagonism, is life-threatening. While prompt diagnosis of NMS is critical, it may be obscured by other diagnoses, such as malignant catatonia, with overlapping, life-threatening symptoms. Initiation of dopamine-blocking agents such as antipsychotics and abrupt cessation of dopaminergic medications such as amantadine can precipitate NMS. Once NMS is suspected, deft medical management should ensue. Multiple case reports detail electroconvulsive therapy's (ECT's) effectiveness in the treatment of NMS. While this relationship is well-documented, there is less literature regarding comparative efficacy of ECT in the acute treatment of NMS-like states precipitated by withdrawal of dopamine agonists, such as amantadine. Case: We present a 52-year-old female with schizoaffective disorder bipolar type, with a history of a lorazepam-resistant catatonic episode the prior year that had responded to amantadine. She presented febrile with altered mental status, lead pipe rigidity, mutism, grasp reflex, stereotypy, autonomic instability, and a Bush-Francis Catatonia Rating Scale (BFCRS) of 24, suggesting malignant catatonia versus NMS. There was concern over a potentially abrupt cessation of her amantadine of which she had been prescribed for the past year. Interventions: Organic etiologies were ruled out, and a presumptive diagnosis of NMS was made with central dopaminergic depletion from abrupt dopamine agonist (amantadine) withdrawal as the suspected underlying etiology. After intravenous lorazepam and reinduction of amantadine failed to alleviate her symptoms, urgent ECT was initiated. Our patient received an index series of ECT of seven treatments. After ECT #1 she was no longer obtunded, after treatment #2 her symptoms of mutism, rigidity, stereotypy, and agitation showed improvement, and by ECT #3, the NMS had rapidly dissipated as evidenced by stable vital signs, lack of rigidity, and coherent conversation. Conclusion: Brisk identification of potentially life-threatening NMS and NMS-like states, including malignant catatonia, warrants a trial of ECT. ECT's theoretical mechanisms of action coincide with the theoretical pathophysiology of the conditions. It is a viable and safe treatment option for reducing mortality. With prompt initiation of ECT, we obtained rapid control of a condition with a potentially high mortality.info:eu-repo/semantics/publishedVersio

The Impact of Olfactory Disorders in the United Kingdom

Olfactory disorders are believed to affect 5% of the general population and have been shown to bear significant psychosocial consequences to sufferers. Although more common than blindness and profound deafness in the United Kingdom, the impact of these disorders has not been assessed to date and the plight of British patients has yet to be quantified. In 2012, a patient support organization, Fifth Sense, was founded to provide information and support to sufferers of chemosensory disorders. Following a recent members conference, a survey of the membership was conducted anonymously using a series of questions based on an existing olfactory disorders questionnaire. From 496 respondents, this has demonstrated high rates of depression (43%) and anxiety (45%), impairment of eating experience (92%), isolation (57%), and relationship difficulties (54%). Women appear to have significantly more issues than men in terms of social and domestic dysfunction relating to olfactory loss (P = 0.01). Qualitative disorders also affected more than 1 in 5 members with parosmia reported in 19% and phantosmia in 24%. This paper discusses the details of the British story of anosmia and other related disorders as depicted by those most affected

Recent Progress in Stimuli-Responsive Antimicrobial Electrospun Nanofibers

Electrospun nanofibrous membranes have garnered significant attention in antimicrobial applications, owing to their intricate three-dimensional network that confers an interconnected porous structure, high specific surface area, and tunable physicochemical properties, as well as their notable capacity for loading and sustained release of antimicrobial agents. Tailoring polymer or hybrid-based nanofibrous membranes with stimuli-responsive characteristics further enhances their versatility, enabling them to exhibit broad-spectrum or specific activity against diverse microorganisms. In this review, we elucidate the pivotal advancements achieved in the realm of stimuli-responsive antimicrobial electrospun nanofibers operating by light, temperature, pH, humidity, and electric field, among others. We provide a concise introduction to the strategies employed to design smart electrospun nanofibers with antimicrobial properties. The core section of our review spotlights recent progress in electrospun nanofiber-based systems triggered by single- and multi-stimuli. Within each stimulus category, we explore recent examples of nanofibers based on different polymers and antimicrobial agents. Finally, we delve into the constraints and future directions of stimuli-responsive nanofibrous materials, paving the way for their wider application spectrum and catalyzing progress toward industrial utilization

Identification and characterization of PhbF: A DNA binding protein with regulatory role in the PHB metabolism of Herbaspirillum seropedicae SmR1

<p>Abstract</p> <p>Background</p> <p><it>Herbaspirillum seropedicae </it>SmR1 is a nitrogen fixing endophyte associated with important agricultural crops. It produces polyhydroxybutyrate (PHB) which is stored intracellularly as granules. However, PHB metabolism and regulatory control is not yet well studied in this organism.</p> <p>Results</p> <p>In this work we describe the characterization of the PhbF protein from <it>H. seropedicae </it>SmR1 which was purified and characterized after expression in <it>E. coli</it>. The purified PhbF protein was able to bind to eleven putative promoters of genes involved in PHB metabolism in <it>H. seropedicae </it>SmR1. <it>In silico </it>analyses indicated a probable DNA-binding sequence which was shown to be protected in DNA footprinting assays using purified PhbF. Analyses using <it>lacZ </it>fusions showed that PhbF can act as a repressor protein controlling the expression of PHB metabolism-related genes.</p> <p>Conclusions</p> <p>Our results indicate that <it>H. seropedicae </it>SmR1 PhbF regulates expression of <it>phb</it>-related genes by acting as a transcriptional repressor. The knowledge of the PHB metabolism of this plant-associated bacterium may contribute to the understanding of the plant-colonizing process and the organism's resistance and survival <it>in planta</it>.</p

Computational modelling of cancerous mutations in the EGFR/ERK signalling pathway

This article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2009 Orton et al.BACKGROUND: The Epidermal Growth Factor Receptor (EGFR) activated Extracellular-signal Regulated Kinase (ERK) pathway is a critical cell signalling pathway that relays the signal for a cell to proliferate from the plasma membrane to the nucleus. Deregulation of the EGFR/ERK pathway due to alterations affecting the expression or function of a number of pathway components has long been associated with numerous forms of cancer. Under normal conditions, Epidermal Growth Factor (EGF) stimulates a rapid but transient activation of ERK as the signal is rapidly shutdown. Whereas, under cancerous mutation conditions the ERK signal cannot be shutdown and is sustained resulting in the constitutive activation of ERK and continual cell proliferation. In this study, we have used computational modelling techniques to investigate what effects various cancerous alterations have on the signalling flow through the ERK pathway. RESULTS: We have generated a new model of the EGFR activated ERK pathway, which was verified by our own experimental data. We then altered our model to represent various cancerous situations such as Ras, B-Raf and EGFR mutations, as well as EGFR overexpression. Analysis of the models showed that different cancerous situations resulted in different signalling patterns through the ERK pathway, especially when compared to the normal EGF signal pattern. Our model predicts that cancerous EGFR mutation and overexpression signals almost exclusively via the Rap1 pathway, predicting that this pathway is the best target for drugs. Furthermore, our model also highlights the importance of receptor degradation in normal and cancerous EGFR signalling, and suggests that receptor degradation is a key difference between the signalling from the EGF and Nerve Growth Factor (NGF) receptors. CONCLUSION: Our results suggest that different routes to ERK activation are being utilised in different cancerous situations which therefore has interesting implications for drug selection strategies. We also conducted a comparison of the critical differences between signalling from different growth factor receptors (namely EGFR, mutated EGFR, NGF, and Insulin) with our results suggesting the difference between the systems are large scale and can be attributed to the presence/absence of entire pathways rather than subtle difference in individual rate constants between the systems.This work was funded by the Department of Trade and Industry (DTI), under their Bioscience Beacon project programme. AG was funded by an industrial PhD studentship from Scottish Enterprise and Cyclacel

Inhaled tobramycin solution-associated recurrent eosinophilia and severe persistent bronchospasm in a patient with cystic fibrosis: a case report

BACKGROUND: Delivery of tobramycin by inhalation to the lungs of patients with cystic fibrosis (CF) who are infected with Pseudomonas aeruginosa has been proven to be effective and safe. The aerosol administration allows high concentrations of tobramycin to be delivered to the site of infection with limited systemic absorption. In rare patients, systemic absorption of inhaled tobramycin may be significant enough to produce toxic effects, such as renal and vestibular toxicities. CASE PRESENTATION: We report a patient with CF who developed recurrent eosinophilia and severe persistent bronchospasm following repeated administration of preservative-free tobramycin by inhalation, beginning at 16 months of age. Also, he developed similar signs and symptoms when he was administered tobramycin intravenously on one occasion at 5 1/2 years. The patient had a history of environmental allergies. Temporal sequence of his signs and symptoms after each administration of tobramycin (similar to re-challenge testing), and his improvement after discontinuation of the drug strongly suggest an adverse drug reaction. CONCLUSION: Hypersensitivity reaction should be considered in patients who develop recurrent eosinophilia and deterioration of pulmonary function following the use of tobramycin by inhalation or by intravenous administration

Nitrogen uptake and internal recycling in Zostera marina exposed to oyster farming: eelgrass potential as a natural biofilter

Oyster farming in estuaries and coastal lagoons frequently overlaps with the distribution of seagrass meadows, yet there are few studies on how this aquaculture practice affects seagrass physiology. We compared in situ nitrogen uptake and the productivity of Zostera marina shoots growing near off-bottom longlines and at a site not affected by oyster farming in San Quintin Bay, a coastal lagoon in Baja California, Mexico. We used benthic chambers to measure leaf NH4 (+) uptake capacities by pulse labeling with (NH4)-N-15 (+) and plant photosynthesis and respiration. The internal N-15 resorption/recycling was measured in shoots 2 weeks after incubations. The natural isotopic composition of eelgrass tissues and vegetative descriptors were also examined. Plants growing at the oyster farming site showed a higher leaf NH4 (+) uptake rate (33.1 mmol NH4 (+) m(-2) day(-1)) relative to those not exposed to oyster cultures (25.6 mmol NH4 (+) m(-2) day(-1)). We calculated that an eelgrass meadow of 15-16 ha (which represents only about 3-4 % of the subtidal eelgrass meadow cover in the western arm of the lagoon) can potentially incorporate the total amount of NH4 (+) excreted by oysters (similar to 5.2 x 10(6) mmol NH4 (+) day(-1)). This highlights the potential of eelgrass to act as a natural biofilter for the NH4 (+) produced by oyster farming. Shoots exposed to oysters were more efficient in re-utilizing the internal N-15 into the growth of new leaf tissues or to translocate it to belowground tissues. Photosynthetic rates were greater in shoots exposed to oysters, which is consistent with higher NH4 (+) uptake and less negative delta C-13 values. Vegetative production (shoot size, leaf growth) was also higher in these shoots. Aboveground/belowground biomass ratio was lower in eelgrass beds not directly influenced by oyster farms, likely related to the higher investment in belowground biomass to incorporate sedimentary nutrients

Safety, immunogenicity, and transplacental antibody transport of conjugated and polysaccharide pneumococcal vaccines administered to pregnant women with HIV: a multicentre randomised controlled trial

Background: Pneumococcus remains an important cause of morbidity in pregnant women with HIV and their infants. We compared the safety and immunogenicity of PCV-10 and PPV-23 with placebo administered in pregnancy. Methods: This double-blind, multicentre, randomised controlled trial was done at eight outpatient clinics in Brazil. Eligible participants were adult women with HIV who were pregnant at a gestational age between 14 weeks and less than 34 weeks and who were taking antiretroviral therapy at study entry. Participants were randomly assigned (1:1:1) to receive either PCV-10, PPV-23, or placebo. Participants and study teams were unaware of treatment allocation. Antibodies against seven vaccine serotypes in PCV-10 and PPV-23 were measured by ELISA. The primary outcomes were maternal and infant safety assessed by the frequency of adverse events of grade 3 or higher; maternal seroresponse (defined as ≥2-fold increase in antibodies from baseline to 28 days after immunisation) against five or more serotypes; and infant seroprotection (defined as anti-pneumococcus antibody concentration of ≥0·35 μg/mL) against five or more serotypes at 8 weeks of life. The study was powered to detect differences of 20% or higher in the primary immunological outcomes between treatment groups. This trial is registered with ClinicalTrials.gov, NCT02717494. Findings: Between April 1, 2016, and Nov 30, 2017, we enrolled 347 pregnant women with HIV, of whom 116 were randomly assigned to the PCV-10 group, 115 to the PPV-23 group, and 116 to the placebo group. One participant in the PCV-10 group did not receive the vaccine and was excluded from subsequent analyses. The frequency of adverse events of grade 3 or higher during the first 4 weeks was similar in the vaccine and placebo groups (3% [90% CI 1–7] for the PCV-10 group, 2% [0–5] for the PPV-23 group, and 3% [1–8] for the placebo group). However, injection site and systemic grade 2 adverse reactions were reported more frequently during the first 4 weeks in the vaccine groups than in the placebo group (14% [9–20] for the PCV-10 group, 7% [4–12] for the PPV-23 group, and 3% [1–7] for the placebo group). The frequency of grade 3 or higher adverse effects was similar across maternal treatment groups (20% [14–27] for the PCV-10 group, 21% [14–28] for the PPV-23 group, and 20% [14–27] for the placebo group). Seroresponses against five or more serotypes were present in 74 (65%) of 114 women in the PCV-10 group, 72 (65%) of 110 women in the PPV-23 group, and none of the 113 women in the placebo group at 4 weeks post vaccination (p<0·0001 for PPV-23 group vs placebo and PCV-10 group vs placebo). Seroresponse differences of 20% or higher in vaccine compared with placebo recipients persisted up to 24 weeks post partum. At birth, 76 (67%) of 113 infants in the PCV-10 group, 62 (57%) of 109 infants in the PPV-23 group, and 19 (17%) of 115 infants in the placebo group had seroprotection against five or more serotypes (p<0·0001 for PPV-23 vs placebo and PCV-10 vs placebo). At 8 weeks, the outcome was met by 20 (19%) of 108 infants in the PCV-10 group, 24 (23%) of 104 infants in the PPV-23 group, and one (1%) of 109 infants in the placebo group (p<0·0001). Although a difference of 20% or higher compared with placebo was observed only in the infants who received PPV-23 at 8 weeks of life, the difference between the two vaccine groups was not appreciable. Interpretation: PCV-10 and PPV-23 were equally safe and immunogenic in pregnant women with HIV and conferred similar levels of seroprotection to their infants. In areas in which childhood PCV administration decreased the circulation of PCV serotypes, PPV-23 administration to pregnant women with HIV might be more advantageous than PCV by virtue of including a broader range of serotypes

Three-Dimensional Printing of a Scalable Molecular Model and Orbital Kit for Organic Chemistry Teaching and Learning

Three-dimensional (3D) chemical models are a well-established learning tool used to enhance the understanding of chemical structures by converting two-dimensional paper or screen outputs into realistic three-dimensional objects. While commercial atom model kits are readily available, there is a surprising lack of large molecular and orbital models that could be used in large spaces. As part of a program investigating the utility of 3D printing in teaching, a modular size-adjustable molecular model and orbital kit was developed and produced using 3D printing and was used to enhance the teaching of stereochemistry, isomerism, hybridization, and orbitals