IgG4-related disease: Case report and 6-year follow-up of an elusive diagnosis mimicking malignancy.

Key Clinical Message: IgG4-related disease is a rare and emerging pathology, characterized by the appearance of pseudotumors. Due to the ability to mimic other pathologies, it is essential to consider it as a differential diagnosis in multisystemic processes. The diagnosis is challenging, requiring a multidisciplinary approach, to minimize the associated morbidity and mortality. Abstract: IgG4-related disease (IgG4-RD) is a rare, emerging, systemic and chronic pathology, characterized by the appearance of pseudotumors resulting from tissue infiltration by IgG4-positive plasma cells that promote eosinophilic inflammation of the tissue with subsequent fibrosis. We present the case of a male, 45-year-old patient, with marked weight loss and skin pallor detected by his family doctor during a child health consultation of his daughter. When questioned, the patient referred complaints of postprandial discomfort in the left hypochondrium with a feeling of fullness, weight loss, chronic fatigue and hyperhidrosis that had lasted for a month. On physical examination, he was pale, and had pain at palpation of the left hypochondrium. Laboratory data showed increased inflammation markers, abdominal ultrasound and CT demonstrated numerous enlarged lymph nodes in the upper quadrants, raising concern for a malignant lymphoproliferative process. Serological, imaging, clinical and laparoscopic excisional biopsy revealed features of IgG4-related disease and excluded malignant lymphoproliferative disease. The immediate response to treatment with oral prednisolone 30 mg/day also contributed for diagnosis confirmation. Due to refractory disease after gradual prednisolone reduction, second-line therapy with rituximab was initiated. Over the 6 years of follow-up, the patient presented multiple exacerbations characterized by the emergence of systemic symptoms, being maintained under close clinical and imaging follow-up by reumathology, infectious diseases, and family medicine specialists.

Assessing the environmental impacts of three different types of accommodations in Portugal and Spain by using an LCA approach.

The tourism industry, affected by COVID-19, must reduce greenhouse gas emissions. This study evaluated the environmental impact of three hotels in coastal and mountainous regions of Spain and Portugal using Life Cycle Assessment (LCA). Data was gathered via surveys in the Greentour tool. Results indicate that the 2-star hotel (focused on cultural-urban tourism) has the highest impacts in most categories, except for CC, FRD, and POF indicators. The 3-star hotel (beach tourism) contributes the most to CC and FRD indicators, while the hostel (nature-religious tourism) has the highest value in the POF indicator. LCA findings reveal that diesel consumption in the hostel and electricity usage in both the 2-star and 3-star hotels are major contributors to environmental impacts across various categories. Overall, evidence suggests that fossil fuel and electricity usage significantly affect tourism activities environmentally. Interestingly, this study highlights that a 2-star hotel can have a higher carbon footprint (CC indicator) compared to a 3-star hotel, challenging the notion that higher star ratings imply lower environmental impact.

Diosmetin attenuates fibromyalgia-like symptoms in a reserpine-induced model in mice.

Fibromyalgia is a potentially disabling idiopathic disease characterized by widespread chronic pain associated with comorbidities such as fatigue, anxiety, and depression. Current therapeutic approaches present adverse effects that limit adherence to therapy. Diosmetin, an aglycone of the flavonoid glycoside diosmin found in citrus fruits and the leaves of Olea europaea L., has antinociceptive, anti-inflammatory, and antioxidant properties. Here, we investigated the effect of diosmetin on nociceptive behaviors and comorbidities in an experimental fibromyalgia model induced by reserpine in mice. To induce the experimental fibromyalgia model, a protocol of subcutaneous injections of reserpine (1 mg/kg) was used once a day for three consecutive days in adult male Swiss mice. Mice received oral diosmetin on the fourth day after the first reserpine injection. Nociceptive (mechanical allodynia, muscle strength, and thermal hyperalgesia) and comorbid (depressive-like and anxiety behavior) parameters were evaluated. Potential adverse effects associated with diosmetin plus reserpine (locomotor alteration, cataleptic behavior, and body weight and temperature changes) were also evaluated. Oral diosmetin (0.015-1.5 mg/kg) reduced the mechanical allodynia, thermal hyperalgesia, and loss of muscle strength induced by reserpine. Diosmetin (0.15 mg/kg) also attenuated depressive-like and anxiety behaviors without causing locomotor alteration, cataleptic behavior, and alteration in weight and body temperature of mice. Overall, diosmetin can be an effective and safe therapeutic alternative to treat fibromyalgia symptoms, such as pain, depression and anxiety.

An interpretable machine learning system for colorectal cancer diagnosis from pathology slides.

Considering the profound transformation affecting pathology practice, we aimed to develop a scalable artificial intelligence (AI) system to diagnose colorectal cancer from whole-slide images (WSI). For this, we propose a deep learning (DL) system that learns from weak labels, a sampling strategy that reduces the number of training samples by a factor of six without compromising performance, an approach to leverage a small subset of fully annotated samples, and a prototype with explainable predictions, active learning features and parallelisation. Noting some problems in the literature, this study is conducted with one of the largest WSI colorectal samples dataset with approximately 10,500 WSIs. Of these samples, 900 are testing samples. Furthermore, the robustness of the proposed method is assessed with two additional external datasets (TCGA and PAIP) and a dataset of samples collected directly from the proposed prototype. Our proposed method predicts, for the patch-based tiles, a class based on the severity of the dysplasia and uses that information to classify the whole slide. It is trained with an interpretable mixed-supervision scheme to leverage the domain knowledge introduced by pathologists through spatial annotations. The mixed-supervision scheme allowed for an intelligent sampling strategy effectively evaluated in several different scenarios without compromising the performance. On the internal dataset, the method shows an accuracy of 93.44% and a sensitivity between positive (low-grade and high-grade dysplasia) and non-neoplastic samples of 0.996. On the external test samples varied with TCGA being the most challenging dataset with an overall accuracy of 84.91% and a sensitivity of 0.996.

Sleep Disorders and Subjective Well-Being in Portuguese Adults: Evidence from a Representative Study.

Objective The quality and quantity of sleep affect people's well-being, as chronic sleep disorders are associated with social, physical, and psychological problems, as well as low self-reported life satisfaction. The present cross-sectional study examined the associations of sleep disorders with self-reported life satisfaction in Portuguese adults. Materials and Methods Data from a representative sample of the Portuguese population (14,341 participants, aged ≥ 18 years) extracted from the Sixth Portuguese National Health Survey was analyzed. Data on subjective well-being and sleep disorders was collected through a questionnaire, and multivariable regression models were performed to examine the associations between these variables, adjusted for potential confounders such as age, gender, level of schooling, degree of urbanization, and family income. Results Sleep disorders were negatively associated with self-reported life satisfaction. Having at least one sleep disturbance in the last two weeks was significantly associated with a 3-point decrease in life satisfaction: ß = -3.0 (95% confidence interval = -3.2--2.7). Discussion Among Portuguese adults, sleep disorders were associated with a decline in life satisfaction. The present study provides new evidence from a representative sample to support the promotion of good sleep hygiene intervention programs.

Involvement of peripheral mast cells in a fibromyalgia model in mice.

Fibromyalgia is a painful disorder of unknown aetiology that presents activation and recruitment of innate immune cells, including mast cells. Efforts have been made to understand its pathogenesis to manage it better. Thus, we explored the involvement of peripheral mast cells in an experimental model of fibromyalgia induced by reserpine. Reserpine (1 mg/kg) was subcutaneously (s.c.) injected once daily in the back of male Swiss mice for three consecutive days. We analysed mechanical and cold allodynia, muscle fatigue and number of mast cell in plantar tissue. The fibromyalgia induction produced mast cell infiltration (i.e., mastocytosis) in the mice's plantar tissue. The depletion of mast cell mediators with the compound 48/80 (0.5-4 mg/kg, intraperitoneal (i.p.)) or the mast cell membrane stabilizer ketotifen fumarate (10 mg/kg, oral route (p.o.) widely (80-90 %) and extensively (from 1 up to 10 days) prevented reserpine-induced mechanical and cold allodynia and muscle fatigue. Compound 48/80 also prevented the reserpine-induced mastocytosis. Finally, we demonstrated that PAR-2, 5-HT2A, 5-HT3, H1, NK1 and MrgprB2 receptors, expressed in neuronal or mast cells, seem crucial to mediate fibromyalgia-related cardinal symptoms since antagonists or inhibitors of these receptors (gabexate (10 mg/kg, s.c.), ENMD-1068 (10 mg/kg, i.p.), ketanserin (1 mg/kg, i.p.), ondansetron (1 mg/kg, p.o.), promethazine (1 mg/kg, i.p.), and L733,060 (5 mg/kg, s.c.), respectively) transiently reversed the reserpine-induced allodynia and fatigue. The results indicate that mast cells mediate painful and fatigue behaviours in this fibromyalgia model, representing potential therapy targets to treat fibromyalgia syndrome.

The Association of Oleic Acid and Dexamethasone Acetate into Nanocapsules Enables a Reduction in the Effective Corticosteroid Dose in a UVB Radiation-Induced Sunburn Model in Mice.

Dexamethasone has a high anti-inflammatory efficacy in treating skin inflammation. However, its use is related to the rebound effect, rosacea, purple, and increased blood glucose levels. Nanotechnology approaches have emerged as strategies for drug delivery due to their advantages in improving therapeutic effects. To reduce dexamethasone-related adverse effects and improve the anti-inflammatory efficacy of treatments, we developed nanocarriers containing this corticosteroid and oleic acid. Nanocapsules and nanoemulsion presented dexamethasone content close to the theoretical value and controlled dexamethasone release in an in vitro assay. Gellan gum-based hydrogels were successfully prepared to employ the nanostructured systems. A permeation study employing porcine skin showed that hydrogels containing non-nanoencapsulated dexamethasone (0.025%) plus oleic acid (3%) or oleic acid (3%) plus dexamethasone (0.025%)-loaded nanocapsules provided a higher amount of dexamethasone in the epidermis compared to non-nanoencapsulated dexamethasone (0.5%). Hydrogels containing oleic acid plus dexamethasone-loaded nanocapsules effectively inhibited mice ear edema (with inhibitions of 89.26 ± 3.77% and 85.11 ± 2.88%, respectively) and inflammatory cell infiltration (with inhibitions of 49.58 ± 4.29% and 27.60 ± 11.70%, respectively). Importantly, the dexamethasone dose employed in hydrogels containing the nanocapsules that effectively inhibited ear edema and cell infiltration was 20-fold lower (0.025%) than that of non-nanoencapsulated dexamethasone (0.5%). Additionally, no adverse effects were observed in preliminary toxicity tests. Our study suggests that nanostructured hydrogel containing a reduced effective dose of dexamethasone could be a promising therapeutic alternative to treat inflammatory disorders with reduced or absent adverse effects. Additionally, testing our formulation in a clinical study on patients with skin inflammatory diseases would be very important to validate our study.

Melanoxetin: A Hydroxylated Flavonoid Attenuates Oxidative Stress and Modulates Insulin Resistance and Glycation Pathways in an Animal Model of Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (DM) continues to escalate, necessitating innovative therapeutic approaches that target distinct pathways and address DM complications. Flavonoids have been shown to possess several pharmacological activities that are important for DM. This study aimed to evaluate the in vivo effects of the flavonoid melanoxetin using Goto-Kakizaki rats. Over a period of 14 days, melanoxetin was administered subcutaneously to investigate its antioxidant, anti-inflammatory, and antidiabetic properties. The results show that melanoxetin reduced insulin resistance in adipose tissue by targeting protein tyrosine phosphatase 1B. Additionally, melanoxetin counteracted oxidative stress by reducing nitrotyrosine levels and modulating superoxide dismutase 1 and hemeoxygenase in adipose tissue and decreasing methylglyoxal-derived hydroimidazolone (MG-H1), a key advanced glycation end product (AGE) implicated in DM-related complications. Moreover, the glyoxalase 1 expression decreased in both the liver and the heart, correlating with reduced AGE levels, particularly MG-H1 in the heart. Melanoxetin also demonstrated anti-inflammatory effects by reducing serum prostaglandin E2 levels, and increasing the antioxidant status of the aorta wall through enhanced acetylcholine-dependent relaxation in the presence of ascorbic acid. These findings provide valuable insights into melanoxetin's therapeutic potential in targeting multiple pathways involved in type 2 DM, particularly in mitigating oxidative stress and glycation.

G Protein-Coupled Receptors and Ion Channels Involvement in Cisplatin-Induced Peripheral Neuropathy: A Review of Preclinical Studies.

Cisplatin is a platinum-based chemotherapy drug widely used to treat various solid tumours. Although it is effective in anti-cancer therapy, many patients develop peripheral neuropathy during and after cisplatin treatment. Peripheral neuropathy results from lesions or diseases in the peripheral somatosensory nervous system and is a significant cause of debilitation and suffering in patients. In recent years, preclinical studies have been conducted to elucidate the mechanisms involved in chemotherapy-induced peripheral neuropathic pain, as well as to promote new therapeutic targets since current treatments are ineffective and are associated with adverse effects. G-protein coupled receptors and ion channels play a significant role in pain processing and may represent promising targets for improving the management of cisplatin-induced neuropathic pain. This review describes the role of G protein-coupled receptors and ion channels in cisplatin-induced pain, analysing preclinical experimental studies that investigated the role of each receptor subtype in the modulation of cisplatin-induced pain.

Increased levels of advanced oxidation protein products (AOPPs) were associated with nociceptive behavior and clinical scores in an experimental progressive autoimmune encephalomyelitis model (PMS-EAE).

Multiple sclerosis (MS) is a neurodegenerative disease that affects the central nervous system (CNS) generating neuropathic pain and anxiety. Primary progressive MS (PPMS) is the most disabling clinical form, and the patients present an intense neurodegenerative process. In this context, the advanced oxidation protein products (AOPPs) are oxidized compounds and their accumulation in plasma has been related to clinical disability in MS patients. However, the involvement of AOPPs in neuropathic pain- and anxiety-like symptoms was not previously evaluated. To assess this, female mice C57BL/6J were used to induce progressive experimental autoimmune encephalomyelitis (PMS-EAE). Clinical score, weight, strength of plantar pressure, rotarod test, mechanical allodynia, and cold hypersensitivity were evaluated before induction (baseline) and on days 7th , 10th , and 14th post-immunization. We assessed nest building, open field, and elevated plus-maze tests 13 days post-immunization. Animals were killed at 14 days post-immunization; then, AOPPs levels, NADPH oxidase, and myeloperoxidase (MPO) activity were measured in the prefrontal cortex, hippocampus, and spinal cord samples. The clinical score increased 14th post-immunization without changes in weight and mobility. Reduced paw strength, mechanical allodynia, and cold allodynia increased in the PMS-EAE animals. PMS-EAE mice showed spontaneous nociception and anxiety-like behavior. AOPPs concentration, NADPH oxidase, and MPO activity increase in CNS structures. Multivariate analyses indicated that the rise of AOPPs levels, NADPH oxidase, and MPO activity influenced the clinical score and cold allodynia. Thus, we indicated the association between non-stimuli painful perception, anxiety-like, and CNS oxidative damage in the PMS-EAE model.

TRPV4 Activation and its Intracellular Modulation Mediated by Kinin Receptors Contribute to Painful Symptoms Induced by Anastrozole.

Anastrozole, an aromatase inhibitor, induces painful musculoskeletal symptoms, which affect patients' quality of life and lead to therapy discontinuation. Efforts have been made to understand the mechanisms involved in these painful symptoms to manage them better. In this context, we explored the role of the Transient Receptor Potential Vanilloid 4 (TRPV4), a potential transducer of several nociceptive mechanisms, in anastrozole-induced musculoskeletal pain in mice. Besides, we evaluated the possible sensibilization of TRPV4 by signalling pathways downstream, PLC, PKC and PKCε from kinin B2 (B2R) and B1 (B1R) receptors activation in anastrozole-induced pain. Anastrozole caused mechanical allodynia and muscle strength loss in mice. HC067047, TRPV4 antagonist, reduced the anastrozole-induced mechanical allodynia and muscle strength loss. In animals previously treated with anastrozole, the local administration of sub-nociceptive doses of the TRPV4 (4α-PDD or hypotonic solution), B2R (Bradykinin) or B1R (DABk) agonists enhanced the anastrozole-induced pain behaviours. The sensitizing effects induced by local injection of the TRPV4, B2R and B1R agonists in animals previously treated with anastrozole were reduced by pre-treatment with TRPV4 antagonist. Furthermore, inhibition of PLC, PKC or PKCε attenuated the mechanical allodynia and muscle strength loss induced by TRPV4, B2R and B1R agonists. The generation of painful conditions caused by anastrozole depends on direct TRPV4 activation or indirect, e.g., PLC, PKC and PKCε pathways downstream from B2R and B1R activation. Thus, the TRPV4 channels act as sensors of extracellular and intracellular changes, making them potential therapeutic targets for alleviating pain related to aromatase inhibitors use, such as anastrozole.

What Feedback Content Do Clinical Teachers Address During OSTEs?

Purpose: How to give feedback is widely taught and assessed during Faculty Development programs. As part of such programs, clinical teachers can attend objective structured teaching sessions (OSTEs), during which they are asked to give feedback to simulated residents on different tasks. Study aimed at: -analysing the feedback content provided during these OSTEs; -evaluating the impact of the training phase, medical discipline, or observed task; -assessing the alignment between feedback content addressed by clinical teachers and content identified as essential by experts. Methods: We conducted a multimethod study. Clinical teachers (N=89) from five departments were trained to give feedback to residents in a six-month training program. Before and after training, they completed three OSTE stations which focused on tasks involving communication, interprofessional, physical exam or procedural skills. We analysed feedback content descriptively. ANOVA test was applied to evaluate feedback contents' influencing factors (ie participants' training phase, medical discipline, type of task addressed). For each OSTE, we analysed the percentage of items identified as essential by 3 experts that were addressed by clinical teachers during the feedback. Results: We analysed 317 feedback sessions and coded 5388 occurrences. Feedback content distribution was: targeted content (73%), other clinical content (20%), learning strategies (4%), and self-management/other (3%). Feedback was often negative (73%). The training phase did not influence the content addressed while the topic of the observed task and clinical teachers' specialization slightly did. Alignment between content identified by experts and addressed by clinical teachers during OSTEs was low (3-38%). Conclusion: Clinical teachers give mostly negative and targeted feedback according to the task. The poor alignment in selecting key content to be addressed is striking and should be further explored since clinical teachers may address elements of competence more according to their personal preferences than to residents' needs and context priorities.

A new species of Orientatractis (Nematoda: Cosmocercoidea: Atractidae) parasite of Yellow-Spotted Amazon River Turtle, Podocnemis unifilis Troschel, 1848 (Testudines: Podocnemididae) in Brazilian Amazon.

The current study describes a new species of nematode, Orientatractis matosi n. sp. (Atractidae), from the stomach and large intestine of Podocnemis unifilis Troschel, 1848 (Testudinidae), collected in the Tocantins and Xingu rivers in the Brazilian state of Pará. The new species was described using light and scanning electron microscopy and differs from its congeners mainly in the number and distribution of the male caudal papillae and by having a shorter right spicule. Orientatracits matosi n. sp. is the eleventh species of the genus Orientatractis Petter, 1966, the third reported from the Amazon, and the second described from P. unifilis.

Topical application of a TRPA1 antagonist reduced nociception and inflammation in a model of traumatic muscle injury in rats.

Musculoskeletal pain is a widely experienced public healthcare issue, especially after traumatic muscle injury. Besides, it is a common cause of disability, but this pain remains poorly managed. However, the pathophysiology of traumatic muscle injury-associated pain and inflammation has not been fully elucidated. In this regard, the transient receptor potential ankyrin 1 (TRPA1) has been studied in inflammatory and painful conditions. Thus, this study aimed to evaluate the antinociceptive and anti-inflammatory effect of the topical application of a TRPA1 antagonist in a model of traumatic muscle injury in rats. The mechanical trauma model was developed by a single blunt trauma impact on the right gastrocnemius muscle of Wistar male rats (250-350 g). The animals were divided into four groups (Sham/Vehicle; Sham/HC-030031 0.05%; Injury/Vehicle, and Injury/HC-030031 0.05%) and topically treated with a Lanette® N cream base containing a TRPA1 antagonist (HC-030031, 0.05%; 200 mg/muscle) or vehicle (Lanette® N cream base; 200 mg/muscle), which was applied at 2, 6, 12, 24, and 46 h after muscle injury. Furthermore, we evaluated the contribution of the TRPA1 channel on nociceptive, inflammatory, and oxidative parameters. The topical application of TRPA1 antagonist reduced biomarkers of muscle injury (lactate/glucose ratio), spontaneous nociception (rat grimace scale), inflammatory (inflammatory cell infiltration, cytokine levels, myeloperoxidase, and N-acetyl-ß-D-glucosaminidase activities) and oxidative (nitrite levels and dichlorofluorescein fluorescence) parameters, and mRNA Trpa1 levels in the muscle tissue. Thus, these results demonstrate that TRPA1 may be a promising anti-inflammatory and antinociceptive target in treating muscle pain after traumatic muscle injury.

Biodistribution and intestinal inflammatory response following voluntary oral intake of silver nanoparticles by C57BL/6J mice.

Silver nanoparticles (AgNP) are among the most widely commercialized nanomaterials globally, with applications in medicine and the food industry. Consequently, the increased use of AgNP in the food industry has led to an unavoidable rise  in human exposure to these nanoparticles. Their widespread use raises concerns about potential hazards to human health, specifically their intestinal pro-inflammatory effects. Thus, the main objective of this study was to evaluate the biological effects of two subacute doses of 5 nm polyvinylpyrrolidone (PVP)-AgNP in C57BL/6J mice. One mg/kg body weight or 10 mg/kg bw was provided once a day for 14 days, using a new technology (HaPILLness) that allows voluntary, stress-free, and accurate oral dosing. It was observed that after oral ingestion, while AgNP is biodistributed throughout the entire organism, most of the ingested dose is excreted in the feces. The passage and accumulation of AgNP throughout the intestine instigated a prominent inflammatory response, marked by significant histological, vascular, and cellular transformations. This response was driven by the activation of the nuclear factor-кB (NF-кB) inflammatory pathway, ultimately leading to the generation of multiple cytokines and chemokines.

Life cycle assessment to address the environmental impacts of tourism in a Spanish tourist destination: The case of Rias Baixas (Galicia) holidays.

Tourism has grown steadily in recent decades, becoming a strategic sector for the economy in many countries. However, the environmental impacts associated with tourism have also experienced an upward trend. In this sense, innovation is needed in the tourism sector, to move towards new models and strategies that integrate environmental sustainability with the social aspects of the sector. In this study, a holistic assessment of the environmental impact of tourism has been carried out using the Life Cycle Assessment (LCA) method, considering all stages of tourism activity: transportation from the place of origin to destination and back, accommodation, catering, and activities conducted. For this purpose, a case study has been carried out based on a typical trip made from Madrid to Rías Baixas (Galicia), considering a four-night stay and the performance of two activities (music festival and cultural museum) at the destination. Two alternative transportation scenarios (train or plane) have been defined to analyze the influence of the type of transportation on the overall impact. Other touristic activities such as visiting gardens or thermal baths instead of visiting a cultural museum or attending a music festival have been analyzed and it has been found that the thermal baths and the museum have the greatest environmental impacts. Transportation was the biggest contributor to most of the environmental impacts in the selected categories. On the other hand, the stay at the destination has stood out due to the impact of the consumption of food and energy used at the accommodation facility. The impact of the activities conducted at the destination is also worth highlighting. Finally, alternative scenarios for transportation have shown that the mode of transportation selected is key for lowering the overall environmental impact of the stay at the destination, highlighting the public transportation alternative, such as the train, as the most environmentally friendly option.

Exploring health care professionals' experiences and knowledge of woman-centred care in a university hospital.

Inspired by the six quality-of-care goals developed by the Institute of Medicine, woman-centred care (WCC) as model of care is used in maternity services as it gives an emphasis on the woman as an individual and not her status as a patient. Bringing stronger attention to women's needs and values, is proven to have clear benefits for perinatal outcomes, but fails to be known or recognised by healthcare professionals' (HCPs) and implemented. Using a mixed-methods approach, this study aimed to explore HCPs definitions of WCC and identify the degree of agreement and knowledge regarding perinatal indicators when a WCC model of care is implemented. The quantitative part was carried using a self-administered questionnaire with perinatal indicators identified from the literature. Semi-structured interviews were realized using a purposive sample of 15 HCPs and an interview grid inspired by Leap's WCC model. The study was conducted in the maternity of a university hospital in French-speaking part of Switzerland. Out of 318 HCPs working with mothers and their newborns, 51% had already heard of WCC without being familiar with Leap's model. The HCPs were aware of the positive perinatal care outcomes when WCC was implemented: women's satisfaction (99.2%), health promotion (97.6%), HCP's job satisfaction (93.2%) and positive feelings about their work (85.6%), which were strongly emphasised in the interviews. The respondents reported institutional difficulties in implementing the model such as administrative overload and lack of time. The positive outcomes of WCC on spontaneous deliveries and improved neonatal adaptation were known by most HCPs (63.4% and 59.9%, respectively). However, fewer than half of the HCPs highlighted the model's positive effects on analgesia and episiotomies or its financial benefits. Knowledge of quality-of-care outcomes (i.e women's satisfaction, positive impact on practice…) was prevalent among most of HCPs. Without adhering to a common definition and without a specific model for consensus, most providers have integrated some aspects of WCC into their practice. However, specific perinatal indicators remain largely unknown, which may hinder the implementation of WCC.

Kinin B2 Receptor Mediates Cisplatin-Induced Painful Peripheral Neuropathy by Intracellular Kinase Pathways and TRPA1 Channel Sensitisation.

Chemotherapy-induced peripheral neuropathy is a severe clinical problem frequently associated with cisplatin use. Although its pathophysiology is poorly understood, it is known that kinin receptors and the transient receptor potential ankyrin 1 (TRPA1) channel play a significant role in the peripheral neuropathy induced by cisplatin in rodents. However, the role of signalling pathways downstream from B2 kinin receptors activation and sensitisation of the TRPA1 channel remains unknown in this model. The cisplatin-induced neuropathy model caused mechanical and cold allodynia in male Swiss mice. Antagonists for kinin B2 and B1 receptors and the TRPA1 channel attenuated the painful parameters. Local sub-nociceptive doses of kinin B2 receptor (bradykinin) and TRPA1 channel (allyl isothiocyanate; AITC) agonists enhanced the painful parameters in cisplatin-treated mice, which their respective antagonists attenuated. Furthermore, we demonstrated the interaction between the kinin B2 receptor and the TRPA1 channel in cisplatin-induced peripheral neuropathy since phospholipase C (PLC) and protein kinase C epsilon (PKCε) inhibitors attenuated the increase in mechanical and cold allodynia evoked by bradykinin and AITC in cisplatin-treated mice. Therefore, regulating the activation of signalling pathways downstream from the kinin B2 receptors activation and TRPA1 channel sensitisation can mitigate the painful peripheral neuropathy decurrent of the oncology treatment with cisplatin.