Molecular characterization of resistance to rifampicin in clinical isolates of Neisseria meningitidis

Among 3904 meningococcal isolates collected between October 2002 and June 2007 by the French Meningococcal Reference Centre, eight (0.20%) were resistant to rifampicin (Rif-R; MIC >1 mg/L) and 27 (0.69%) were intermediate-resistant to rifampicin (Rif-I; MICs between 0.38 mg/L and 1 mg/L) according to the E-test method. The MICs determined by agar dilution were lower, eliminating the E-test intermediate category. All Rif-R isolates had mutations in the rpoB gene, resulting in substitutions at or near amino acid position 552, which were absent in non-resistant isolates. These data suggest that a rifampicin clinical breakpoint of 1.0 mg/L should be adopted for Neisseria meningitidis .     

Drug repurposing and emerging adjunctive treatments for schizophrenia

Introduction: Schizophrenia is a frequent disorder, which substantially impairs patients’ quality of life. Moreover, the burden of illness for patients, their families and for the society, in general, is substantial. Nevertheless, the understanding of the pathophysiology of this syndrome, concise diagnostic methods and more effective and tolerable treatments are still lacking. Thus, innovative approaches and the exploration of new territories are required.

Areas covered: An overview of repurposed drugs and emerging treatments for schizophrenia is presented, focusing on randomized, controlled trials and meta-analyses.

Expert opinion: Despite many years of drug research, several needs in the treatment of schizophrenia including the safety and tolerability, stage-dependent and personalized approaches, as well as drug delivery and sustainability have not been addressed sufficiently. Given the current failure of a number of mechanistically new drugs, repurposed compounds may serve as alternative and/or adjunctive agents for schizophrenic patients and for treatment refractory patients in particular. Anti-inflammatory drugs (e.g., acetylsalicylic acid, celecoxib and minocycline), as well as N-acetylcysteine, a precursor of the major antioxidant glutathione, hormones (e.g., estrogen, raloxifene and oxytocin), glutamatergic (e.g., glycine and d-serine) and nicotinergic compounds, ‘nutraceuticals’ (e.g., ω-3 fatty acids) and cannabidiol, an endocannabinoidmodulator, represent promising agents in this field.     

Sudden gains among women receiving treatment for alcohol use disorders

Understanding the timing and types of change during treatment for mental health disorders is an important step toward elucidating possible mechanisms of behaviour change in response to therapeutic interventions, yet these issues have not been adequately addressed in the alcohol dependence treatment literature. The current study applied sudden gains (SGs) methodology, an approach originally developed in depression treatment studies, to a sample of women receiving treatment for alcohol use disorders. SGs are drastic improvements in symptoms that occur between two psychotherapy sessions and are hypothesised to be the result of what occurred in the first of those two sessions. SGs can happen at any time during the course of treatment, can happen more than once, and are individualised, as opposed to aggregated for a sample. For the current study, SGs were examined across three variables: percent drinking days (PDD), urge frequency (UF), and urge intensity (UI) in a sample of 102 women receiving either individual or couple cognitive-behavioural therapy for alcohol use disorders. Results indicated the presence of SGs; one-third of the sample experienced at least one SG in either alcohol use or urges to drink; the most common SGs were in frequency of urges to drink. SGs in urge frequency during treatment predicted better post-treatment drinking outcome.     

Phase Diagram of Sodium Hexametaphosphate and Poly(allylamine hydrochloride) Mixtures and In Situ Monitoring of Step‐by‐Step Deposition in This Polyelectrolyte System

The step‐by‐step deposition of poly(allylamine hydrochloride) (PAH) and sodium hexameta­phosphate (PSP) leads to coatings displaying interesting intumescent properties and is a fascinating model system to understand the fundamental mechanism behind such a deposition process. In this investigation, the deposition kinetics of (PAH‐PSP)_n is followed in situ by means of a quartz crystal microbalance with dissipation monitoring, as a function of NaCl concentration. The evolution of the film deposition is analyzed in detail and the data are compared with previous data obtained by ellipsometry on dried films. These results are also compared with the expectations from the PAH/PSP phase diagram. The (PAH‐PSP)_n films are also able to incorporate hexacyanoferrate anions with an amount of an incorporated redox probe reflecting the film thickness as obtained in the presence of eletrolyte solutions of increasing ionic strength. The in situ measurements and the electrochemical probe experiments reveal details of the film deposition mechanism that are not accessible by dry‐state characterization methods.

     

Mechanisms of antimicrobial resistance among hospital-associated pathogens

Introduction: The introduction of antibiotics revolutionized medicine in the 20th-century permitting the treatment of once incurable infections. Widespread use of antibiotics, however, has led to the development of resistant organisms, particularly in the healthcare setting. Today, the clinician is often faced with pathogens carrying a cadre of resistance determinants that severely limit therapeutic options. The genetic plasticity of microbes allows them to adapt to stressors via genetic mutations, acquisition or sharing of genetic material and modulation of genetic expression leading to resistance to virtually any antimicrobial used in clinical practice.

Areas covered: This is a comprehensive review that outlines major mechanisms of resistance in the most common hospital-associated pathogens including bacteria and fungi.

Expert commentary: Understanding the genetic and biochemical mechanisms of such antimicrobial adaptation is crucial to tackling the rapid spread of resistance, can expose unconventional therapeutic targets to combat multidrug resistant pathogens and lead to more accurate prediction of antimicrobial susceptibility using rapid molecular diagnostics. Clinicians making treatment decisions based on the molecular basis of resistance may design therapeutic strategies that include de-escalation of broad spectrum antimicrobial usage, more focused therapies or combination therapies. These strategies are likely to improve patient outcomes and decrease the risk of resistance in hospital settings.     

Understanding Interactions Between Chinese Medicines and Pharmaceutical Drugs in Integrative Healthcare

In the 21 st century,the public are more informed,mainly via the Internet,about health and medical products and have become more knowledgeable about matters relating to their health conditions and well-being in curing and preventing illnesses.They often self-medicate themselves with various health products and over-the-counter(OTC) medicines apart from prescribed pharmaceutical drugs(PD).Some of those non-prescribed products may have doubtful quality control and contain harmful additives or unchecked ingredients;thus their usefulness is in doubt.The increasing popularity world-wide of using Chinese medicines(CM) and related OTC functional products has raised concerns over their concomitant use with PD and the consequential adverse effects.In most cases the alleged causes of adverse effects are linked with herbal sources,although the authorised information on the interactions between CM-PD is not plentiful in the literature.There is an urgent need for such a data base.The future professionals in health and medical care should be knowledgeable or aware of what their patients have been taking or given.In actual practice the patients may receive both treatments intentionally or unintentionally,with or without the awareness of the practitioner.In these situations a reliable database for interactions between CM-PD will be extremely useful for consultation when treatment problems appear or during emergency situations.Their combining of medications may be involved with possible outcomes of adverse reactions or beneficial effects.Such a database will be welcomed by both practitioners of herbal medicines and orthodox medicine practitioners in the emerging trend of integrative medicine.The author has been involved in various research projects of basic and clinical aspects in mainly CM among other herbal and PD.Examples will be given largely on those related to these disciplines as illustrations in this overview.     

Acute liver injury in COVID-19 patients hospitalized in the intensive care unit: Narrative review

In recent years, humanity has been confronted with a global pandemic due to coronavirus disease 2019 (COVID-19), which has caused an unprecedented health and economic crisis worldwide. Apart from the respiratory symptoms, which are considered the principal manifestations of COVID-19, it has been recognized that COVID-19 constitutes a systemic inflammatory process affecting multiple organ systems. Across the spectrum of organ involvement in COVID-19, acute liver injury (ALI) has been gradually gaining increasing attention by the international scientific community. COVID-19 associated liver impairment can affect a considerable proportion of COVID-19 patients and seems to correlate with the severity of the disease course. Indeed, COVID-19 patients hospitalized in the intensive care unit (ICU) run a greater risk of developing ALI due to the severity of their clinical condition and in the context of multi-organ failure. The putative pathophysiological mechanisms of COVID-19 induced ALI in ICU patients remain poorly understood and appear to be multifactorial in nature. Several theories have been proposed to explain the occurrence of ALI in the ICU setting, such as hypoperfusion and ischemia due to hemodynamic instability, passive liver congestion as a result of congestive heart failure, ischemia-reperfusion injury, hypoxia due to respiratory failure, mechanical ventilation itself, sepsis and septic shock, cytokine storm, endotheliitis with concomitant coagulopathy, drug-induced liver injury, parenteral nutrition and direct cytopathic viral effect. It should be noted that no specific therapy for COVID-19 induced ALI exists. Therefore, the therapeutic approach lies in preventive measures and is exclusively supportive once ALI ensues. The aim of the current review is to scrutinize the existing evidence on COVID-19 associated ALI in ICU patients, explore its clinical implications, shed light on the underlying pathophysiological mechanisms and propose potential therapeutic approaches. Ongoing research on the particular scientific field will further elucidate the pathophysiology behind ALI and address unresolved issues, in the hope of mitigating the tremendous health consequences imposed by COVID-19 on ICU patients.     

Improved short-term memory and increased expression of NR2B observed in senescence-accelerated mouse (SAM) P6

The increased dopamine and serotonin were suggested [Niimi et al., 2008. Emotional behavior and expression pattern of tyrosine hydroxylase and tryptophan hydroxylase in senescence-accelerated mouse (SAM) P6 mice. Behav. Brain Res. 188, 329-336], and as these monoamines are well known to influence working memory processes, SAMP6 may show improved working memory. We found that spatial Y-maze memory and non-spatial novel object recognition memory of SAMP6 were improved compared with those of senescence-accelerated mouse resistant 1 (SAMR1). Among molecules known to be related with memory processes other than dopamine and serotonin, we focused on N-methyl-d-aspartate (NMDA) receptors. Animals treated with (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), a NMDA receptor antagonist, were subjected to the Y-maze and novel object recognition tests to examine whether NMDA receptors are associated with the improved short-term memory of SAMP6. CPP (10mg/kg) significantly impaired the spontaneous alternation behavior and the exploratory preference of SAMR1, whereas no significant effect was seen in SAMP6 in either of these behavioral tests. Western blot analyses revealed increased expression of NMDA receptor (NR) subunit 2B in forebrain of SAMP6 compared with SAMR1, while there was no difference in the levels of NR1 and NR2A between SAMR1 and SAMP6. Our results indicate that increased expression of NR2B in forebrain of SAMP6 is one of the causes of the improved short-term memory of SAMP6.     

Difficulties associated with Reporting Radiographer working practices – A narrative evidence synthesis

ObjectivesThis narrative synthesis of evidence identifies and explores issues that impact upon the expansion or effectiveness of Reporting Radiographers working in all diagnostic modalities within the United Kingdom (UK). The publication focuses on working practices affecting trainees and qualified Reporting Radiographers.Key findingsFourteen studies informed the themes of this article, they were published between 2014 and 2021.Delays to commencement of reporting roles and variance in performance monitoring was common. Lack of formalisation, overly restrictive and out of date scopes of practice were also found. Whilst, staffing shortages contributed to underutilisation. Failure to utilise skills was most prevalent in cross sectional imaging modalities. Considerable variance in practice was also found between centres. Meanwhile, Reporting Radiographer involvement in professional development, education and research is far from universal and often dependant on individuals sacrificing their own time.ConclusionGovernance in many centres would benefit from renewal and standardisation, particularly relating to scopes of practice and performance monitoring audits. Measures are also required to encourage compliance with guidance, address staffing issues and reduce variation between centres. Failure to address these issues has the potential to impair collaboration, delay patient care and increase economic inefficiencies whilst negatively impacting satisfaction for service users and staff.Lack of involvement in professional development, education and research suggests Reporting Radiographers are not accomplishing their full potential, educating the next generation of the reporting workforce and driving evidence-based change for further development of the specialism.Implications for practiceBetter use of the existing workforce is essential to increase productivity, value, and security of Reporting Radiographer services, which are essential to improve patient outcomes and efficiency.