Antimicrobial activity of enacyloxin IIa and gladiolin against the urogenital pathogens Neisseria gonorrhoeae and Ureaplasma spp.

AIMS: To determine the antimicrobial activity of enacyloxin IIa and gladiolin against Neisseria gonorrhoeae and Ureaplasma spp. METHODS AND RESULTS: The Burkholderia polyketide antibiotics enacyloxin IIa and gladiolin were tested against 14 N. gonorrhoeae and 10 Ureaplasma spp. isolates including multidrug-resistant N. gonorrhoeae isolates WHO V, WHO X and WHO Z as well as macrolide, tetracycline and ciprofloxacin-resistant ureaplasmas. Susceptibility testing of N. gonorrhoeae was carried out by agar dilution, whereas broth micro-dilution and growth kinetic assays were used for Ureaplasma spp. The MIC range for enacyloxin IIa and gladiolin against N. gonorrhoeae was 0·015-0·06 mg l-1 and 1-2 mg l-1 respectively. The presence of resistance to front line antibiotics had no effect on MIC values. The MIC range for enacyloxin IIa against Ureaplasma spp. was 4-32 mg l-1 with a clear dose-dependent effect when observed using a growth kinetic assay. Gladiolin had no antimicrobial activity on Ureaplasma spp. at 32 mg l-1 and limited impact on growth kinetics. CONCLUSIONS: Enacyloxin IIa and gladiolin antibiotics have antimicrobial activity against a range of antibiotic susceptible and resistant N. gonorrhoeae and Ureaplasma isolates. SIGNIFICANCE AND IMPACT OF THE STUDY: This study highlights the potential for a new class of antimicrobial against pathogens in which limited antibiotics are available. Development of these compounds warrants further investigation in the face of emerging extensively drug-resistant strains.

The expression pattern of a Cav3-Kv4 complex differentially regulates spike output in cerebellar granule cells.

The cerebellum receives sensory information by mossy fiber input from a multitude of sources that require differential signal processing. A compartmentalization of function begins with the segregation of mossy fibers across 10 distinct lobules over the rostrocaudal axis, with tactile receptor afferents prevalent in anterior lobules and vestibular input in caudal lobules. However, it is unclear how these unique signals might be differentially processed at the circuit level across the cerebellum. As granule cells receive mossy fiber input, they represent a key stage at which postsynaptic mechanisms could influence signal processing. Granule cells express an A-type current mediated by Kv4 potassium channels that modify the latency and frequency of spike output. The current study examined the potential for a Cav3 calcium-Kv4 channel complex to regulate the response of granule cells to mossy fiber input in lobules 2 and 9 of the rat cerebellum. Similar A-type currents were recorded in both regions, but the Cav3 calcium current was expressed at a substantially higher density in lobule 9 cells, acting to increase A-type current availability through its influence on Kv4 voltage for inactivation. The difference in excitability imparted by Cav3-Kv4 interactions proves to allow lobule 2 granule cells to respond more effectively to tactile stimulus-like burst input and lobule 9 cells to slow shifts in input frequency characteristic of vestibular input. The expression pattern of Cav3 channels and its control of Kv4 availability thus provides a novel means of processing widely different forms of sensory input across cerebellar lobules.

The Cav3-Kv4 complex acts as a calcium sensor to maintain inhibitory charge transfer during extracellular calcium fluctuations.

Synaptic transmission and neuronal excitability depend on the concentration of extracellular calcium ([Ca](o)), yet repetitive synaptic input is known to decrease [Ca](o) in numerous brain regions. In the cerebellar molecular layer, synaptic input reduces [Ca](o) by up to 0.4 mm in the vicinity of stellate cell interneurons and Purkinje cell dendrites. The mechanisms used to maintain network excitability and Purkinje cell output in the face of this rapid change in calcium gradient have remained an enigma. Here we use single and dual patch recordings in an in vitro slice preparation of Sprague Dawley rats to investigate the effects of physiological decreases in [Ca](o) on the excitability of cerebellar stellate cells and their inhibitory regulation of Purkinje cells. We find that a Ca(v)3-K(v)4 ion channel complex expressed in stellate cells acts as a calcium sensor that responds to a decrease in [Ca]o by dynamically adjusting stellate cell output to maintain inhibitory charge transfer to Purkinje cells. The Ca(v)3-K(v)4 complex thus enables an adaptive regulation of inhibitory input to Purkinje cells during fluctuations in [Ca](o), providing a homeostatic control mechanism to regulate Purkinje cell excitability during repetitive afferent activity.

The Effects of Mindfulness-Based Interventions on Suicide Outcomes: A Meta-Analysis.

Although mindfulness-based interventions (MBIs) have been shown to be effective in treating several psychological difficulties, to date, no review has systematically examined their effectiveness in treating or preventing suicide. The goals of the present study were to (1) evaluate the effectiveness of MBIs in treating suicide and (2) understand how individual characteristics and characteristics of MBIs influence treatment outcomes through a systematic meta-analysis. A search of PubMed, MEDLINE, PsychINFO, and ProQuest Dissertations and Theses was conducted in February 2019. A total of 12 publications (13 studies, n = 627) were included. MBIs demonstrated significant moderate effects on suicidal ideation in pre-post studies and small effects in controlled studies. In addition, MBIs demonstrated significant moderate effects in both samples of individuals with histories of depression and histories of suicidal ideation or attempts. Moreover, MBIs led to clinically significant reductions in suicidal ideation and depression. Female participants, older samples, and longer treatments showed greater treatment effects, although these relationships were weak. Results suggest that MBIs may be promising treatments for suicidal ideation; however, more research is needed to establish the effects of these treatments as well as the mechanisms through which MBIs reduce suicide.

The interaction and interference of preformed metal crowns on magnetic resonance imaging: a scoping review with a systematic methodology.

PURPOSE: Preformed metal crowns are widely used to restore primary and permanent teeth. Children may require magnetic resonance imaging (MRI) for diagnosis and monitoring of diseases in the head and neck region. Metallic objects, in the field of view, may compromise the diagnostic value of an MRI. The impact on the diagnostic quality of an MRI in children who have had preformed metal crowns placed has not been assessed. The aim of this systematic review was to evaluate the impact that PFMCs have on MRI imaging quality and thus the overall diagnostic value. METHODS: Electronic searches of the following databases were completed: MEDLINE, EMBASE, Cochrane Library, Web of Science and Open Grey. Primary in vivo studies on children who had at least one preformed metal crown placed and required an MRI investigation were to be included. PRISMA guidelines were followed and screening/data extraction was carried out by two independent calibrated reviewers. RESULTS: A total of 7665 articles were identified. After removing duplicates, 7062 were identified for title and abstract screening. Thirty-four articles underwent full-text review, of which none met the inclusion criteria. Most common reasons for exclusion were not placing preformed metal crowns (n = 16) or in vitro studies (n = 12). CONCLUSION: No in vivo studies were identified to establish the hypothetical impact preformed metal crowns would have on the diagnostic quality of an MRI in the head and neck region. Decision making needs to be guided on a case by case basis. Further high-quality clinical studies are required.

Review of the Dockery procedure for lateral ankle instability. A seven-year retrospective analysis.

This article presents a critical review of the Dockery procedure (autogenous peroneus longus free graft technique) for the treatment of lateral ankle instability. Those patients with gastrocnemius equinus were treated with gastrocnemius recession during surgery. The authors reviewed 33 stabilizations performed over a period of 7 years to analyze the effectiveness of the procedure with and without the addition of the gastrocnemius recession. Assessed were the type and length of conservative therapy, the time to return to regular activity, complications experienced, and the recurrence rate. The results show a reinjury rate of 3%. The complications included infection, prolonged healing, and occasional screw irritation requiring screw removal. In light of the low incidence of reinjury, this technique is a valid procedure for treating lateral ankle instability.

Dental cone beam CT image quality possibly reduced by patient movement.

Patient artefacts in dental cone beam CT scans can happen for various reasons. These range from artefacts from metal restorations to movement. An audit was carried out in the Glasgow Dental Hospital analysing how many scans showed signs of "motion artefact", and then to assess if there was any correlation between patient age and movement artefacts. Specific age demographics were then analysed to see if these cohorts were at a higher risk of "movement artefacts".

Expression of inhibin/activin proteins and receptors in the human hypothalamus and basal forebrain.

The inhibin/activin family of proteins is known to have a broad distribution of synthesis and expression in many species, as well as a variety of functions in reproductive and other physiological systems. Yet, our knowledge regarding the production and function of inhibin and activin in the central nervous system is relatively limited, especially in humans. The present study aimed to explore the distribution of inhibin/activin protein subunits and receptors in the adult human brain. The human hypothalamus and surrounding basal forebrain was examined using post-mortem tissues from 29 adults. Immunocytochemical studies were conducted with antibodies directed against the inhibin/activin α, ßA, and ßB subunits, betaglycan and the activin type IIA and IIB receptors. An immunoassay was also utilised to measure dimeric inhibin A and B levels in tissue homogenates of the infundibulum of the hypothalamus. Robust ßA subunit immunoreactivity was present in the paraventricular, supraoptic, lateral hypothalamic, infundibular, dorsomedial and suprachiasmatic nuclei of the hypothalamus, in the basal ganglia, and in the nucleus basalis of Meynert. A similar staining distribution was noted for the ßB subunit, betaglycan and the type II receptor antibodies, whereas α subunit staining was not detected in any of the major anatomical regions of the human brain. Inhibin B immunoreactivity was present in all tissues, whereas inhibin A levels were below detectable limits. These studies show for the first time that the inhibin/activin protein subunits and receptors can be co-localised in the human brain, implicating potential, diverse neural functions.

Case report: Cone-beam ct imaging in the management of a double tooth.

BACKGROUND: The diagnosis and management strategies of double teeth have largely relied on clinical examination and conventional radiographic findings. Cone-Beam Computed Tomography (Cone-beam CT) was developed in the late 1990's and, therefore, is a relatively recent addition to the imaging armamentarium for use in Maxillofacial Radiology. There have been no publications in the dental literature demonstrating the use of Cone-beam CT or 3D stereolithography in the diagnosis and surgical planning of the management of double teeth. CASE REPORT: An 11 year old girl presented with a double left lateral maxillary incisor. Conventional plain film radiography failed to provide the requisite information for pre-operative planning. Cone-beam Computed Tomography (Cone-beam CT) allowed determination of location of fusion, three-dimensional (3D) visualisation of pulpal anatomy and the construction of a 3D stereolithographic model for surgical planning. The double tooth was surgically divided in situ under local analgesia. The redundant distal unit was extracted and the residual mesial unit built up in composite resin following physiological mesial drift of displaced maxillary left canine. No endodontic therapy was required. FOLLOW-UP: At a 10-month follow-up visit, clinical and radiographic vitality and success was noted. CONCLUSION: The great amount of radiological information which Cone-beam CT can offer not only improves pre-operative and surgical planning, but the 3D models provided can be used to further educate and inform patients and guardians in the management of double teeth.

Major salivary gland agenesis in a young child: consequences for oral health.

BACKGROUND: Salivary gland agenesis is a rare condition. It can be associated with some equally rare syndromes so that diagnosis can be delayed. CASE REPORT: The authors describe a case report. A 3-year-old girl, presented with dry mouth, carious teeth, recurrent herpes labialis and tonsillitis to Newcastle Dental Hospital. This case highlights the diagnostic and therapeutic challenges posed by 'salivary gland agenesis'. CONCLUSION: Primary and secondary paediatric healthcare professionals should be aware of the possibility of salivary gland agenesis in the setting of the 'non drooling baby'. Early detection of 'salivary gland agenesis' would do much to prevent the deleterious oral affects which follow the absence of salivary protection in the oral cavity.

Using surgical outcomes data.

The measurement of expanded outcomes data is continuing. As managed care continues to spread through the United States and competition increases, an increased emphasis will be placed on the importance of collecting and analyzing outcomes data as a way to assess and ensure quality of care. Surgeons must familiarize themselves with the concepts behind the measurement of outcomes data and involve themselves in the development of outcomes indicators for surgery in order to ensure a continuing high level of surgical care is provided to their patients.