Understanding the clinical reasoning processes involved in the management of multimorbidity in an ambulatory setting: study protocol of a stimulated recall research.

BACKGROUND: Primary care physicians are at the very heart of managing patients suffering from multimorbidity. However, several studies have highlighted that some physicians feel ill-equipped to manage these kinds of complex clinical situations. Few studies are available on the clinical reasoning processes at play during the long-term management and follow-up of patients suffering from multimorbidity. This study aims to contribute to a better understanding on how the clinical reasoning of primary care physicians is affected during follow-up consultations with these patients. METHODS: A qualitative research project based on semi-structured interviews with primary care physicians in an ambulatory setting will be carried out, using the video stimulated recall interview method. Participants will be filmed in their work environment during a standard consultation with a patient suffering from multimorbidity using a "button camera" (small camera) which will be pinned to their white coat. The recording will be used in a following semi-structured interview with physicians and the research team to instigate a stimulated recall. Stimulated recall is a research method that allows the investigation of cognitive processes by inviting participants to recall their concurrent thinking during an event when prompted by a video sequence recall. During this interview, participants will be prompted by different video sequence and asked to discuss them; the aim will be to encourage them to make their clinical reasoning processes explicit. Fifteen to twenty interviews are planned to reach data saturation. The interviews will be transcribed verbatim and data will be analysed according to a standard content analysis, using deductive and inductive approaches. CONCLUSION: Study results will contribute to the scientific community's overall understanding of clinical reasoning. This will subsequently allow future generation of primary care physicians to have access to more adequate trainings to manage patients suffering from multimorbidity in their practice. As a result, this will improve the quality of the patient's care and treatments.

Women's experiences of sexual functioning in the early weeks of breast cancer treatment.

This study describes women's sexual functioning in the early weeks of breast cancer treatment and the possible sexual changes that women may experience compared with pre-treatment functioning. Seventy-five patients filled out a questionnaire on sexual functioning and participated in a semi-structured interview on changes in sexual life and intimacy after treatment. Sixty-two women were sexually active before treatment; three post-treatment patterns of sexual behaviour were identified: 22.6% of these women were as active as before treatment, 35.5% stopped any sexual activity and 41.9% experienced quantitative and qualitative changes. Analyses showed that each pattern had specific characteristics regarding current sexual functioning, the kinds of changes reported (e.g. decreased frequency and increased tenderness) and the reasons for these changes (e.g. tiredness and sex not a priority). Even in the immediate post-surgical period, women may react in very different ways to treatment in terms of sexual functioning. Most women experience changes, but cessation of sexual activity is not inevitable. Positive changes (growing tenderness and affection) also exist. These important interindividual differences require a person-centred approach when the topic of sexuality is being addressed, and practitioners need to be sensitive to individual perceptions of change. Early detection of sexual changes may prevent the crystallisation of difficulties over time.

SARS-CoV-2 infection does not induce HIV viral escape in the central nervous system: A case series.

We report two cases of HIV positive patients with SARS-CoV-2 infection and a recent diagnosis of opportunistic infections of central nervous system (CNS). We investigated the potential impact of coinfection with SARS-CoV-2 on HIV replication in CNS.

Reversible changes in goldfish brain polyamine concentrations and synthetic enzymes after cold exposure.

Exposure of goldfish to the cold (5 degrees C) caused a sharp increase in brain putrescine level during the first week. Such increase continued at a minor rate for the whole period of exposure (2 months). In contrast, the content of spermidine and spermine remained unchanged. Putrescine increase was concomitant with a remarkable rise in ornithine decarboxylase activity (ODC), which reached a maximum stimulation after 1 week of cold exposure, and declined thereafter, remaining significantly higher than the control for the entire period of study. Cold exposure caused also a reduction of S-adenosylmethionine decarboxylase (AdoMetDC) activity and an increase of ornithine level, whereas methionine content was unchanged. When fish exposed to cold temperature were returned to 20 degrees C, the modifications observed on brain polyamine metabolism were completely reversed. Supported by previous observations, our results suggest that the changes in the polyamine metabolism induced in goldfish brain by cold exposure could represent an homeostatic mechanism carried out by the goldfish to minimize the possible effects of thermal changes.

Predominant expression of group-II metabotropic glutamate receptors in the goldfish brain.

Group-II metabotropic glutamate (mGlu) receptors (mGlu2/3 receptors) were highly expressed in various regions (telencephalon, optic tectum, and cerebellum, but not vagal lobe) of the goldfish brain. In the goldfish telencephalon, expression of mGlu2/3 receptors was even higher than in the rat cerebral cortex. In contrast, mGlu5 receptors showed low levels of expression in all goldfish brain regions, whereas mGlu1a receptors were only expressed in the goldfish cerebellum. Pharmacological activation of group-II mGlu receptors with the selective agonists, 2R,4R-4-aminopyrrolidine-2, 4-dicarboxylic acid and (2S,2'R,3'R)-2-(2,3-dicarboxycyclopropyl) glycine, reduced the evoked release of glutamate from goldfish brain synaptosomes, whereas agonists of group-I and -III mGlu receptors (3, 5-dihydroxyphenylglycine and L-2-amino-4-phosphonobutanoate) were inactive. The predominance of group-II over group-I mGlu receptors in the goldfish brain may provide a natural defense against excitotoxic neuronal death and contribute to the unusually high resistance of goldfish against hypoxic brain damage.

Pharmacological characterization of adenosine A1 receptors and its functional role in brown trout (Salmo trutta) brain.

The adenosine receptor agonist N(6)-cyclohexyl[(3)H]adenosine ([(3)H]CHA) was used to identify and pharmacologically characterize adenosine A1 receptors in brown trout (Salmo trutta) brain. In membranes prepared from trout whole brain, the A1 receptor agonist [(3)H]CHA bound saturably, reversibly and with high affinity (K(d)=0. 69+/-0.04 nM; B(max)=0.624+/-0.012 pmol/mg protein) to a single class of binding sites. In equilibrium competition experiments, the adenosine agonists and antagonists all displaced [(3)H]CHA from high-affinity binding sites with the rank order of potency characteristic for an adenosine A1 receptors. A1 receptor density appeared not age-related (from 3 months until 4 years), and was similar in different brain areas. The specific binding was inhibited by guanosine 5'-triphosphate (IC(50)=0.778+/-0.067 microM). GTP (5 microM) induced a low affinity state of A1 receptors. In superfused trout cerebral synaptosomes, 30 mM K(+) stimulated the release of glutamate in a calcium dependent manner. Glutamate-evoked release was dose-dependently reduced by CHA, and the inhibition was reversed by the A1 antagonist 8-cyclopentyltheophylline (CPT). In the same synaptosomal preparation, 30 mM K(+) as well as 1 mM glutamate stimulated the release of adenosine in a Ca(2+)-independent manner and tetrodotoxin insensitive. These findings show that in trout brain adenosine A1 receptors are present which are involved in the modulation of glutamate transmitter release. Moreover, the stimulation of adenosine release by K(+) depolarisation or glutamate support the hypothesis that, as in mammalian brain, a cross-talk between adenosine and glutamate systems exists also in trout brain.

The calcium-dependent [3H]acetylcholine release from synaptosomes of brown trout (Salmo trutta) optic tectum is inhibited by adenosine A1 receptors: effects of enucleation on A1 receptor density and cholinergic markers.

Presynaptic inhibition is one of the major control mechanisms in the CNS. Previously we reported that A1 adenosine receptors are highly concentrated in the brain, including optic tectum, of trout and that they inhibited the release of glutamate. The optic tectum is heavily innervated by cholinergic nerve terminals. We have investigated whether A1 receptors inhibit the presynaptic release of acetylcholine and whether the inhibition is triggered by calcium. The release of [3H]ACh evoked by 30 mM KCl was Ca2+ dependent and it was dose-dependently inhibited by the A1 adenosine receptor agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) ranging between 10 nM to 100 microM. The maximum of inhibition was reached at 10 microM. The A1 receptor antagonist 8-cyclopentyltheopylline (CPT, 10 microM), reversed almost completely the inhibition induced by CCPA 10 microM. In Fura-2/AM loaded synaptosomes, K(+) depolarization raised [Ca2+](i) by about 64%. CCPA (10 microM) reduced the K(+)-evoked Ca2+ influx increase by about 48% and this effect was completely antagonised by CPT 10 microM. Synaptosome pretreatment with different Ca2+ channel blockers differently affected K(+)-evoked Ca2+ influx. This was not significantly modified by nifedipine (1 microM, L-type blocker) nor by omega-agatoxin IVA (0.3 microM, P/Q-type blocker), whereas about 50% reduction was shown by 0.5 microMomega-conotoxin GVIA (N-type blocker). Neurochemical parameters associated with cholinergic transmission and the density of A(1) adenosine receptors were measured in the trout optic tectum 12 days after unilateral eye ablation. A significant drop of both acetylcholinesterase (AChE) activity (24%) and choline acetyltransferase (CAT) activity (32%) was observed in deafferentated optic tectum, whereas the high affinity choline uptake did not parallel the decrease in enzyme activity. Eye ablation caused a marked decrease (43%) of A1 receptor density without changing the affinity. The K(+)-evoked release of [3H]ACh from synaptosomes of deafferentated was not modify as well as the efficacy of 10 microMCCPA in decreasing [3H]ACh release was not apparently modified.

Effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in goldfish cerebellum: neurochemical and immunocytochemical analysis.

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administered in goldfish for 3 consecutive days (10 mg kg-1 i.p.), caused cerebellar disappearance of dopamine-hydroxylase (DBH) immunoreactive fibres, whereas the noradrenergic cell bodies located in the medulla oblongata appeared intact. This effect was coupled with marked decreases in cerebellar noradrenaline (NA) and dopamine (DA) levels. An increase of immunostaining for glial fibrillary acidic protein (GFAP) was also observed. In the cerebellum of MPTP-treated fish, the contents of glutamate and GABA were significantly reduced, whereas glutamine was strongly increased. These modifications were concomitant with a significant increase of glutamine synthetase (GS) activity, whereas glutamic acid decarboxylase (GAD) activity was decreased. No changes in choline acetyltransferase (ChAT) and ornithine decarboxylase (ODC) activities were observed. High affinity uptake of glutamate and GABA was strongly reduced. Pretreatment of fish with either the monoamine oxidase inhibitor pargyline or the catecholamine (CA) uptake blocker mazindol largely prevented such modifications. The NMDA-sensitive glutamate receptor uncompetitive antagonist, dizocilpine maleate (MK-801), failed to protect against MPTP-induced damage. In conclusion, the neurotoxic effects of MPTP in goldfish cerebellum appear to be not specific against catecholaminergic terminals and could promote astrocytic reactions.

Creutzfeldt-Jakob disease associated with the R208H mutation in the prion protein gene.

The authors investigated a patient who died of apparent sporadic Creutzfeldt-Jakob disease (CJD) but carried a R208H substitution in the prion protein (PrP). The patient phenotype was indistinguishable from typical sporadic CJD (i.e., MM1 subtype). In addition, pathologic PrP, PrP(Sc), originated from both the normal and the mutated PRNP allele and had the same characteristics as PrP(Sc) type 1. The authors propose that the R208H mutation influences disease susceptibility without significantly affecting PrP(Sc) properties or disease phenotype.

Neurochemical changes in cerebellum of goldfish exposed to various temperatures.

Acclimation of goldfish at 35 degrees C increased the cerebellar content of aspartate, glutamate, and taurine and [3H]glutamate uptake. Acclimation at 4 degrees C increased the levels of glutamine, serine, and alanine and glutamine synthetase (GS) activity. Adenosine content increased in cerebellum of fish acclimated to warm temperature. K+-evoked release of endogenous and exogenous glutamate from cerebellar slices increased in fish acclimated at 35 degrees C compared to 4 degrees C. The basal level of cyclic adenosine 3':5'-monophosphate (cAMP) in perfused cerebellar slices in fish acclimated at 35 degrees C was much higher than in fish acclimated at 5 degrees and 22 degrees C. It is concluded that variations of environmental temperature produces large neurochemical changes in goldfish cerebellum.