Longitudinal Modeling of Bacterial Sexually Transmitted Infections Among Sexual Minority Men Living with HIV.

Bacterial sexually transmitted infections (BSTIs) are largely preventable, yet their rates remain high across the U.S., particularly among sexual minority men (SMM) living with HIV (LWH). We explored longitudinal factors associated with BSTI acquisition in a national online sample of SMM LWH with recent suboptimal adherence to antiretroviral therapy (ART) or virologic non-suppression, such as spread within sexual networks, drug use in a sexual context (chemsex), and mental health issues. Participants completed online surveys over 12 months as part of an eHealth intervention. Over 12 months, 30% of participants self-reported at least one BSTI, with 28-45% reporting recurrent infections in consecutive surveys. Using generalized estimating equations with a binomial distribution and an exchangeable correlation structure, we found that BSTI accumulation was associated with chemsex, a higher number of anal sex partners, participation in exchange sex, and depressive symptoms. To reduce the burden of BSTIs among SMM LWH, public health initiatives and clinical settings should adopt a comprehensive sexual health approach, addressing chemsex, exchange sex, and associated mental health conditions. Addressing these factors can mitigate BSTI recurrence and improve overall sexual health among SMM LWH.

Spatially and Temporally Resolved Detection of Arsenic in a Capillary Dielectric Barrier Discharge by Hydride Generation High-Resolved Optical Emission Spectrometry.

A new method for arsenic detection by optical emission spectrometry (OES) is presented. Arsine (AsH3) is generated from liquid solutions by means of hydride generation (HG) and introduced into a capillary dielectric barrier discharge (DBD) where it is atomized and excited. A great challenge in OES is the reduction of the recorded background signal, because it negatively affects the limit of detection (LOD). In conventional DBD/OES methods, the signal intensity of the line of interest, in this case arsenic, is integrated over a long time scale. However, due to the pulsed character of the plasma, the plasma on-time is only a small fraction of the integration time. Therefore, a high amount of noise is added to the actual signal in each discharge cycle. To circumvent this, in the present study the emitted light from the DBD is collected by a fast gated iCCD camera, which is mounted on a modified monochromator. The experimental arrangement enables the recording of the emission signal of arsenic in the form of a monochromatic 2D-resolved picture. The temporal resolution of the iCCD camera in the nanosecond range provides the information at which point in time and how long arsenic is excited in the discharge. With use of this knowledge, it is possible to integrate only the arsenic emission by temporally isolating the signal from the background. With the presented method, the LOD for arsenic could be determined to 93 pg mL-1 with a calibration curve linear over 4 orders of magnitude. As a consequence, the developed experimental approach has a potential for both mechanistic studies of arsine atomization and excitation in DBD plasmas as well as routine applications, in which arsenic determination at ultratrace levels is required.

Flexible Microtube Plasma (FµTP) as an Embedded Ionization Source for a Microchip Mass Spectrometer Interface.

Dielectric barrier discharges are used as soft ionization sources for mass spectrometers or ion mobility spectrometers, enabling excellent possibilities for analytical applications. A new robust and small-footprint discharge design, flexible microtube plasma (FµTP), developed as a result of ongoing miniaturization and electrode design processes, is presented in this work. This design provides major safety benefits by fitting the electrode into an inert flexible fused silica capillary (tube). Notably, in this context, the small discharge dimensions enable very low gas flows in the range of <100 mL min-1; portability; the use of hydrogen, nitrogen, and air in addition to noble gases such as helium and argon, including its mixtures with propane; and application in microchip environments. By coupling FµTP with gas chromatography/mass spectrometry, we show that the polarity principle of the new discharge design allows it to outperform established ionization sources such as dielectric barrier discharge for soft ionization (DBDI) and low-temperature plasma (LTP) at low concentrations of perfluoroalkanes in terms of sensitivity, ionization efficiency, chemical background, linear dynamic range, and limit of detection by a large margin. In negative ion mode, the limit of detection is improved by more than 3-fold compared with that of DBDI and by 8-fold compared with that of LTP. The protonation capability was evaluated by headspace measurements of diisopropyl methylphosphonate in positive ion mode, showing low fragmentation and high stability in comparison to DBDI and LTP.

Soft Argon-Propane Dielectric Barrier Discharge Ionization.

Dielectric barrier discharges (DBDs) have been used as soft ionization sources (DBDI) for organic mass spectrometry (DBDI-MS) for approximately ten years. Helium-based DBDI is often used because of its good ionization efficiency, low ignition voltage, and homogeneous plasma conditions. Argon needs much higher ignition voltages than helium when the same discharge geometry is used. A filamentary plasma, which is not suitable for soft ionization, may be produced instead of a homogeneous plasma. This difference results in N2, present in helium and argon as an impurity, being Penning-ionized by helium but not by metastable argon atoms. In this study, a mixture of argon and propane (C3H8) was used as an ignition aid to decrease the ignition and working voltages, because propane can be Penning-ionized by argon metastables. This approach leads to homogeneous argon-based DBDI. Furthermore, operating DBDI in an open environment assumes that many uncharged analyte molecules do not interact with the reactant ions. To overcome this disadvantage, we present a novel approach, where the analyte is introduced in an enclosed system through the discharge capillary itself. This nonambient DBDI-MS arrangement is presented and characterized and could advance the novel connection of DBDI with analytical separation techniques such as gas chromatography (GC) and high-pressure liquid chromatography (HPLC) in the near future.

Tuning Soft Ionization Strength for Organic Mass Spectrometry.

Besides the progress of new mass spectrometer technologies, the investigation and development of soft ionization sources play an important key role for analytical sciences. Since the dielectric barrier discharge ionization (DBDI) is identified as two temporally separated events, a selective prevention of the coincident plasma can lead to improved ionization strength. Although a DBDI is known as a soft ionization source, a modulation of the high-voltage amplitude and duty cycle can lead to optimized ionization strength. This is an advantage to cover different types of analytes.

Capillary Dielectric Barrier Discharge: Transition from Soft Ionization to Dissociative Plasma.

A capillary He dielectric barrier discharge was investigated with respect to its performance as a soft or dissociative ionization source. Spatiotemporal measurements of the plasma emission showed that in one voltage duty cycle the plasma evolved from a soft to dissociative ionization source. At the earliest time, the soft plasma was generated between the electrodes as well as outside the capillary forming the plasma jet. It was characterized by significant radiation arising only from He and N2(+), which are known to be important in the process of the soft ionization of the analyte. Later in time, the plasma capable of dissociating molecules develops. It is characterized by appreciable radiation from analyte dissociation products and is restricted to the interelectrode region in the capillary. Thus, for the soft ionization purposes, it is feasible to introduce the analyte exclusively in the plasma jet. For elemental analysis, the interelectrode plasma is appropriate.

The Francis Report--Implications for the Education and Training of Dental Professionals.

This paper explores the implications of the Francis Report for education of the dental team. It considers selection of candidates for training, issues relating to the curriculum itself, including assessment and the importance of listening to trainees. The overriding importance of the 'informal' or 'hidden' curriculum, through which students and trainees observe their teachers and develop a sense of the professional and ethical culture within an educational institution, is stressed. Clinical relevance: Sound education, rooted in the recognized ethical principles highlighted in the Francis Report, is essential to the delivery of a dental work force that will deliver care according to the fundamental standards laid down by the GDC.

Sustainable oral healthcare: what is it and how do we achieve it?

In recent years, there has been an increase in interest in what environmental sustainability means for healthcare, including oral health and dentistry. To help facilitate discussions among key stakeholders in this area, the Scottish Dental Clinical Effectiveness Programme held a workshop in November 2022. The purpose of this workshop was to explore current thinking on the subject of sustainability as it relates to oral health and to help stakeholders identify how to engage with the sustainability agenda. This paper presents an overview of the presentations and discussions from the workshop and highlights potential avenues for future work and collaboration.

Oral medicine: 5. Halitosis.

Oral malodour can have a range of causes, though most cases of true malodour have an oral cause, and many others are imagined.

Using live stream technology to conduct workplace observation assessment of trainee dental nurses: an evaluation of effectiveness and user experience.

AIM/OBJECTIVE: This study evaluates the effectiveness and users' experience of using live stream technology to conduct workplace observation assessments of trainee dental nurses. Information on the usability, accessibility, and general satisfaction of this technological technique were collected. MATERIALS AND METHODS: This nationwide cross-sectional survey was conducted in Scotland and included one focus group and three online questionnaires with qualitative and quantitative questions. The quantitative responses were described using standard descriptive analysis, while the quantitative data were investigated using thematic analysis. RESULTS: Eighty-one trainee dental nurses, 35 clinicians and 19 assessors participated in this study. Live stream observation was generally well received by the trainee dental nurses and clinicians, who thought that it had helped increase their confidence to perform practical skills. The assessors also stated that overall satisfaction was high, and that live stream observation met their expectations for efficacy. However, several technical challenges, such as network issues were brought up by responders. CONCLUSION: This study provides evidence that workplace observation assessments can be performed in the future by using live stream technology. However, additional investigation and comparison will aid in determining the most effective way of using this approach and providing feedback to promote learning among dental trainees.

Accelerating GPCR Drug Discovery With Conformation-Stabilizing VHHs.

The human genome encodes 850 G protein-coupled receptors (GPCRs), half of which are considered potential drug targets. GPCRs transduce extracellular stimuli into a plethora of vital physiological processes. Consequently, GPCRs are an attractive drug target class. This is underlined by the fact that approximately 40% of marketed drugs modulate GPCRs. Intriguingly 60% of non-olfactory GPCRs have no drugs or candidates in clinical development, highlighting the continued potential of GPCRs as drug targets. The discovery of small molecules targeting these GPCRs by conventional high throughput screening (HTS) campaigns is challenging. Although the definition of success varies per company, the success rate of HTS for GPCRs is low compared to other target families (Fujioka and Omori, 2012; Dragovich et al., 2022). Beyond this, GPCR structure determination can be difficult, which often precludes the application of structure-based drug design approaches to arising HTS hits. GPCR structural studies entail the resource-demanding purification of native receptors, which can be challenging as they are inherently unstable when extracted from the lipid matrix. Moreover, GPCRs are flexible molecules that adopt distinct conformations, some of which need to be stabilized if they are to be structurally resolved. The complexity of targeting distinct therapeutically relevant GPCR conformations during the early discovery stages contributes to the high attrition rates for GPCR drug discovery programs. Multiple strategies have been explored in an attempt to stabilize GPCRs in distinct conformations to better understand their pharmacology. This review will focus on the use of camelid-derived immunoglobulin single variable domains (VHHs) that stabilize disease-relevant pharmacological states (termed ConfoBodies by the authors) of GPCRs, as well as GPCR:signal transducer complexes, to accelerate drug discovery. These VHHs are powerful tools for supporting in vitro screening, deconvolution of complex GPCR pharmacology, and structural biology purposes. In order to demonstrate the potential impact of ConfoBodies on translational research, examples are presented of their role in active state screening campaigns and structure-informed rational design to identify de novo chemical space and, subsequently, how such matter can be elaborated into more potent and selective drug candidates with intended pharmacology.

[CME-EKG 69: Sinus Pauses in Long-Term Monitoring]. / CME-EKG 69: Sinuspausen im Monitoring CME-Fragen.

CME-EKG 69: Sinus Pauses in Long-Term Monitoring Abstract. While the indication for a pacemaker therapy in patients with high-degree AV block or symptomatic bradycardias is straightforward in most cases, intermittent oligo- and asymptomatic sinus bradycardias and pauses turn out to be more challenging. In this case report potential causes, diagnostic steps and possible therapies will be discussed.

[CME-EKG 69/Answers: Sinus Pauses in Long-Term Monitoring]. / CME-EKG 69/Antworten: Sinuspausen im Monitoring.

CME-EKG 69/Answers: Sinus Pauses in Long-Term Monitoring Abstract. While the indication for a pacemaker therapy in patients with high-degree AV block or symptomatic bradycardias is straightforward in most cases, intermittent oligo- and asymptomatic sinus bradycardias and pauses turn out to be more challenging. In this case report potential causes, diagnostic steps and possible therapies will be discussed.

The highly conserved serine threonine kinase StkP of Streptococcus pneumoniae contributes to penicillin susceptibility independently from genes encoding penicillin-binding proteins.

BACKGROUND: The serine/threonine kinase StkP of Streptococcus pneumoniae is a major virulence factor in the mouse model of infection. StkP is a modular protein with a N-terminal kinase domain a C-terminal PASTA domain carrying the signature of penicillin-binding protein (PBP) and prokaryotic serine threonine kinase. In laboratory cultures, one target of StkP is the phosphoglucosamine mutase GlmM involved in the first steps of peptidoglycan biosynthesis. In order to further elucidate the importance of StkP in S. pneumoniae, its role in resistance to beta-lactams has been assessed by mutational analysis in laboratory cultures and its genetic conservation has been investigated in isolates from infected sites (virulent), asymptomatic carriers, susceptible and non-susceptible to beta-lactams. RESULTS: Deletion replacement mutation in stkP conferred hypersensitivity to penicillin G and was epistatic on mutations in PBP2X, PBP2B and PBP1A from the resistant 9V clinical isolate URA1258. Genetic analysis of 55 clinical isolates identified 11 StkP alleles differing from the reference R6 allele. None relevant mutation in the kinase or the PASTA domains were found to account for susceptibility of the isolates. Rather the minimal inhibitory concentration (MIC) values of the strains appeared to be determined by their PBP alleles. CONCLUSION: The results of genetic dissection analysis in lab strain Cp1015 reveal that StkP is involved in the bacterial response to penicillin and is epistatic on mutations PBP 2B, 2X and 1A. However analysis of the clinical isolates did not allow us to find the StkP alleles putatively involved in determining the virulence or the resistance level of a given strain, suggesting a strong conservation of StkP in clinical isolates.