Qualitative study exploring the experiences and perceptions of dolutegravir/lamivudine dual antiretroviral therapy (the PEDAL study) in people living with HIV: protocol.

INTRODUCTION: Antiretroviral treatment turned HIV infection into a chronic disease and improved quality of life for people living with HIV. Dual-drug combinations have been shown to be effective in suppressing viral replication and can potentially reduce long-term drug-associated toxicities. We aim to investigate patients' perceptions and experiences on the safety, effectiveness, tolerability and unmet needs of the dual-drug combination dolutegravir/lamivudine in Brighton and Hove, UK. In addition, we will conduct a comparative analysis between patients on dolutegravir/lamivudine and patients on other dual-drug and three-drug combinations. Finally, the study aims to provide recommendations to improve doctor-patient communication, knowledge and understanding of the treatment plan, and additional care that ought to be considered in patient-centred, holistic care plans. METHODS AND ANALYSIS: Our qualitative methodological framework is based on three main methods: cultural domain analysis, focus group discussions and in-depth interviews. Cultural domain analysis employs a range of techniques (free listing, pile sorts and rankings) to elicit terms from informants regarding specific cultural domains (ie, groups of items that are perceived to be of the same kind). This framework has been codesigned with a patient representative to ensure relevance, suitability and coproduction of knowledge. All methods have been tested to take place online, as an option, via Zoom, Skype or Microsoft Teams. Padlet, an application to create online boards, will be used during the cultural domain analysis session. Data collected will be analysed following the completion of each method embracing an iterative approach through applied thematic analysis. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Health Research Authority (Reference 21/NW/0070). Findings will be used to produce recommendations to improve doctor and patient communication by identifying patients' fears, worries, misconceptions and general concerns of their drug regimen. Conclusions will be disseminated via journal articles, conference papers and discussions through public engagement events. PROJECT REGISTRATION NUMBER: IRAS number: 286277. NCT04901728.

Fisiopatología de la fibromialgia / Physiopathology of fibromyalgia

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Mercury-Tolerant Ensifer medicae Strains Display High Mercuric Reductase Activity and a Protective Effect on Nitrogen Fixation in Medicago truncatula Nodules Under Mercury Stress.

Mercury (Hg) is extremely toxic for all living organisms. Hg-tolerant symbiotic rhizobia have the potential to increase legume tolerance, and to our knowledge, the mechanisms underlying Hg tolerance in rhizobia have not been investigated to date. Rhizobial strains of Ensifer medicae, Rhizobium leguminosarum bv. trifolii and Bradyrhizobium canariense previously isolated from severely Hg-contaminated soils showed different levels of Hg tolerance. The ability of the strains to reduce mercury Hg2+ to Hg0, a volatile and less toxic form of mercury, was assessed using a Hg volatilization assay. In general, tolerant strains displayed high mercuric reductase activity, which appeared to be inducible in some strains when grown at a sub-lethal HgCl2 concentration. A strong correlation between Hg tolerance and mercuric reductase activity was observed for E. medicae strains, whereas this was not the case for the B. canariense strains, suggesting that additional Hg tolerance mechanisms could be playing a role in B. canariense. Transcript abundance from merA, the gene that encodes mercuric reductase, was quantified in tolerant and sensitive E. medicae and R. leguminosarum strains. Tolerant strains presented higher merA expression than sensitive ones, and an increase in transcript abundance was observed for some strains when bacteria were grown in the presence of a sub-lethal HgCl2 concentration. These results suggest a regulation of mercuric reductase in rhizobia. Expression of merA genes and mercuric reductase activity were confirmed in Medicago truncatula nodules formed by a sensitive or a tolerant E. medicae strain. Transcript accumulation in nodules formed by the tolerant strain increased when Hg stress was applied, while a significant decrease in expression occurred upon stress application in nodules formed by the Hg-sensitive strain. The effect of Hg stress on nitrogen fixation was evaluated, and in our experimental conditions, nitrogenase activity was not affected in nodules formed by the tolerant strain, while a significant decrease in activity was observed in nodules elicited by the Hg-sensitive bacteria. Our results suggest that the combination of tolerant legumes with tolerant rhizobia constitutes a potentially powerful tool in the bioremediation of Hg-contaminated soils.

Determination of chemotherapeutic agents in fish and shellfish by matrix solid-phase dispersion and liquid chromatography-tandem mass spectrometry.

Chemicals are widely used in aquaculture and one of the main recipients of these analytes is the aquatic environment. The aim of this work was to develop and validate a simple and sensitive method for the determination of multiclass chemotherapeutic agents in farmed fish and shellfish using matrix solid-phase dispersion and liquid chromatography-tandem mass spectrometry. Residues of azamethiphos, three avermectins, two carbamates, and two benzoylureas were extracted from samples using silica gel as clean-up adsorbent and 0.5% acetic acid in acetonitrile as elution solvent. The extraction conditions were investigated and optimized using an experimental design. Mass spectrometry detection was carried out in positive electrospray ionization mode with multiple-reaction monitoring scan (except for benzoylurea family). Matrix-matched standards were used for the drugs quantification. Good linearity (R(2) ≥ 0.996) was observed in the range of 5-500 µg kg(-1). Limits of detection were in the range of 1.5-3.7 µg kg(-1). Recoveries from salmon samples spiked with veterinary drugs were in the range 84.9-118%. Precision was satisfactory since relative standard deviations were lower than 10.6%. The method can be successfully applied for the analysis of fish and shellfish from aquaculture.

Transferencia aislada del m. dorsal ancho y del m. redondo menor a través de un abordaje deltopectoral. Descripción e ilustración de la técnica quirúrgica en un caso clínico / Isolated transfer of latissimus dorsi muscle and teres minor muscle by a deltopectoral approach. Description and illustration of surgical technique in a clinical case

Objetivo y método: Se presenta el caso clínico de una paciente de 68 años con una rotura masiva del manguito de los rotadores que mantiene una antepulsión completa y un déficit para la rotación externa del brazo. Se describe e ilustra la técnica quirúrgica de la transferencia conjunta del m. dorsal ancho y del m. redondo menor a través de un abordaje deltopectoral, únicamente con el objetivo de ganar rotación externa. Conclusión: Esta técnica es reproducible, requiere un conocimiento de la anatomía del hombro y puede obtener buenos resultados para el paciente, aunque precisa una prolongada recuperación (AU)

Objective and method: We report the case of 68-year-old woman with a massive tear of the rotator cuffs who underwent joint transfer of the latissimus dorsi muscle and teres minor muscle. The arm was kept immobile in external rotation for six weeks, protecting from internal rotation for 12 weeks. Conclusion: This technique is reproducible and good results can be obtained for the patient, though it requires a prolonged recovery and immobilization uncomfortable for the patient (AU)

Determination of trace levels of aquaculture chemotherapeutants in seawater samples by SPME-GC-MS/MS.

A sensitive and efficient solid-phase microextraction (SPME) method for the determination of organophosphorous (OPPs) and pyrethroid pesticides (Pyrs) in aquaculture-seawater samples by using GC with MS/MS (GC-MS/MS) was developed. Dichlorvos and chlorpyrifos (OPPs); permethrin, alpha-cypermethrin and deltamethrin (Pyrs) were selected according to their use as chemotherapeutants in the aquaculture industry. Different parameters affecting extraction efficiency such as fibre coating, agitation, pH and extraction time profiles were investigated. An experimental central composite design (alpha = 1) and desirability functions were used for the simultaneous optimization of extraction temperature and sample volume. Finally, a method based on direct SPME in 40 min at 75 degrees C using 100-microm-thick poly(dimethyl)siloxane (PDMS) fibre and 20 mL of sample volume is proposed. The method was validated, exhibiting good linearity, precision and accuracy parameters with picogram per millilitre LODs. The proposed methodology was applied to determine the ultratrace levels of OPPs and Pyrs in aquaculture-seawater samples by the standard addition approach, which proved to be reliable and sensitive, in addition to requiring only small amounts of sample.

Supercritical fluid extraction of polyhalogenated pollutants from aquaculture and marine environmental samples: a review.

This article focuses on the state-of-the-art in sample preparation using supercritical fluid extraction (SFE), to monitor the content of polyhalogenated pollutants in aquaculture and marine environmental samples. Marine sediments and biological applications, including several types of samples matrices (fish, shellfish, seaweed and fish feed) and analyte groups (polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), polybrominated diphenylethers (PBDEs), polychlorinated dibenzo-p-dioxin (PCDD)/Fs and organochlorinated pesticide (OCPs)) are discussed with respect to SFE use and optimisation of conditions. We also discuss the great analytical potential of SFE, the integration of the extraction and clean-up steps for rapid sample processing justifying its use for routine work. The most recent SFE applications to the determination of these pollutants in marine environmental (biota and sediment) samples, published in the last 15 years, are reviewed.