R-mandelonitrile-lyase, homolog to Pru d 10, is a major peach allergen in peach allergic Spanish population.

BACKGROUND AND OBJECTIVE: Peach allergy is a prevalent cause of food allergy. Despite the repertoire of allergens available for molecular diagnosis, there are still patients with undetectable IgE levels to peach allergens but presenting symptoms after its ingestion. The objective of this study was to investigate the allergenic profile in a patient population with symptoms produced by peach. METHODS: An exploratory retrospective study was performed with patients presenting symptoms after the ingestion of peach. Forty-two patients were included in the study. The allergenic profile of individual patients was investigated by immunoblot. A serum pool was prepared with the sera that recognized a 70 kDa band. This pool was used to detect this protein in peach peel and pulp and to identify the 70 kDa protein in 2D immunoblot. Spots recognized in the 2D immunoblot were sequenced by LC-MS/MS. Inhibition studies were performed between peach peel and almond. RESULTS: Twenty-two patients (52.4%) recognized the 70 kDa protein in immunoblot. This protein was recognized in peel and pulp. Two different spots were observed in 2D-PAGE, both were identified as (R)-mandelonitrile lyases (RML) with high amino acid similarity with Pru du 10. Peach RML were partially inhibited with an almond extract. No association was found between any reported symptom and sensitization to RML. RML-sensitized patients were older and reported pollen associated respiratory symptoms more frequently than negative patients. CONCLUSION: A new peach allergen, a RML, homologous of Pru du 10, recognized by 52% of the population has been identified.

Post-cure Heat Treatments Influence the Mechanical and Optical Properties of Acrylic and Bis-acryl Composite Resins.

OBJECTIVE: To evaluate the influence of post-cure heat treatments (PCHT) on Knoop microhardness (KHN) and color change of bis-acryl composite resin (Protemp 4 - 3M ESPE, USA and PrimmaArt - FGM, Brazil) and chemically activated acrylic resins (Dencôr - Clássico, Brazil, and Duralay - Cotia, Brazil). METHODS AND MATERIALS: Specimens (12×1 mm) were prepared for each material (n=10/group). Thirty minutes after curing, the specimens were subjected to PCHT for 10 minutes at 70°, 100°, or 130°C. The control group was kept at room temperature (24°C) for the same amount of time. KHN was analyzed 24 hours after PCHT (n=10). Following Commission Internationale de l'Éclairage (CIE) Delta E 2000 (CIEDE2000 [ΔE00]), color measurements were obtained at three time points: 1. after polymerization; 2. after PCHT; and 3. after 30 days of storage in water, coffee, or red wine. Data for each material were analyzed by one-way analysis of variance (ANOVA) (p<0.05). RESULTS: The PCHT at 130°C produced the highest KHN values. Except for the 70°C groups from Dencôr and Protemp, all PCHTs increased the initial color values (p>0.05). In general, chemically activated acrylic resins showed an increase in color stability when subjected to PCHT (p>0.05). For bis-acryl composite resin, PCHT did not influence color stability (p<0.05). CONCLUSION: Overall, the results showed that PCHT increased the tested materials' color changes and Knoop microhardness. However, except for PCHT at 130°C in Duralay, the color changes remained within acceptable values. The PCHT treatment resulted in better color stability for most of the composite resins studied.

Factors associated with the attraction and retention of family and community medicine and nursing residents in rural settings: a qualitative study.

BACKGROUND: The current shortage of primary care doctors and nurses is causing difficulties in replacement, and this shortage is expected to increase. This situation is more pronounced in rural environments than in urban ones. Family and community care specialty training is a key component of both the transition to clinical practice and the retention of new professionals. The aim of this study is to explore the attitudes and perceptions of internal medicine residents and internal nurse residents trained in a rural teaching unit on factors associated with recruitment and retention, including the role of the specialty training programme. METHODS: A qualitative study was conducted. Purposive sampling was used, and thirteen residents from the central Catalonia teaching unit who were in their final year of training participated in semistructured interviews. The data were collected during 2022 and were subsequently analysed with thematic analysis. The study is reported using the COREQ checklist. RESULTS: Six themes emerged from data related to perceptions and attitudes about the factors associated with recruitment and retention: training programme, characteristics of the family and community specialty, concept of rural life, family and relational factors, economic and resource factors, and recruitment and job opportunities. CONCLUSIONS: Family and community medicine and nursing residents trained in rural settings expressed satisfaction with the specialty programme and most features of primary care, but they experienced a wide range of uncertainties in deciding on their professional future in terms of living in rural areas, family support, financial support and recruitment. This study identifies individual and structural factors that could be of great use to retain doctors and nurses in rural areas.

Expert Review and Consensus on the Treat-to-Target Management of Hereditary Angioedema: From Scientific Evidence to Clinical Practice.

BACKGROUND: Hereditary angioedema with C1 inhibitor deficiency (HAE-C1INH) is a rare disease characterized by swelling episodes. It affects quality of life (QOL) and can be fatal when the upper airways are involved. Treatment is individualized, with therapeutic options including on-demand treatment (ODT) and short- and long-term prophylaxis (STP, LTP). However, available guidelines are not always clear about the selection of treatment, the goals of treatment, or how achievement of these goals is assessed. OBJECTIVE: To review available evidence for the management of HAE-C1INH and build a Spanish expert consensus to steer management towards a treat-to-target approach, while addressing some of the less clear aspects of the Spanish guidelines. METHODS: We reviewed the literature on the treat-to-target management of HAE-C1INH, focusing on treatment selection and goals and the tools available to assess whether the goals have been achieved. We discussed the literature based on clinical experience and drew up 45 statements on undefined management aspects. A panel of 53 HAE experts validated the statements through a 2-round Delphi process. RESULTS: The goals for ODT and STP are to minimize the morbidity and mortality of attacks and to prevent attacks caused by known triggers, respectively, while the main goal of LTP is to decrease the rate, severity, and duration of attacks. Furthermore, when prescribing, clinicians should consider the reduction in adverse effects, while increasing patient QOL and satisfaction. Appropriate instruments for assessing achievement of treatment goals are also indicated. CONCLUSIONS: We provide recommendations on previously unclear aspects of HAE-C1INH management with ODT, STP, and LTP, focusing on clinical and patient-oriented goals.

Use of virtual reality compared to the role-playing methodology in basic life support training: a two-arm pilot community-based randomised trial.

INTRODUCTION: Virtual reality (VR) is a technology that allows us to replace our real environment with one created with digital media. This technology is increasingly used in the training of healthcare professionals, and previous studies show that the involvement and motivation of students who participate in activities that use VR increases compared to those who undergo training with the traditional methodology. The main aim of the study is to evaluate the learning curve of the students using a VR environment, to evaluate the satisfaction with the training activity and the cost, and to compare them with training that uses role-playing methodology. METHODOLOGY: Two-arm community-based randomised trial. The control arm will base the training on the usual role-playing methodology. The second arm or intervention arm will base the Basic Life Support (BLS) training on a VR programme. RESULTS: Statistically significant differences are observed in the percentage of correct answers in favour of the group that used VR as a learning methodology in the test taken at the end of the course. These differences disappear when comparing the results of the test performed at six months. The satisfaction rating of the role-playing training activity has a score of 9.37 out of a total of 10 and satisfaction with the VR methodology has a score of 9.72. The cost analysis shows that the cost of training a student by role-playing is 32.5 euros and, if trained by VR, it is 41.6 euros. CONCLUSIONS: VR is a tool that allows the consolidation of a greater amount of knowledge in the short term and can be used for situations such as pandemics, where traditional formats are not available. In relation to student satisfaction with the training activity, the rating in both groups is very high and the differences are minimal. The results will be directly applicable to the decision making of BLS training in Central Catalonia in relation to the scheduling of training activities that use the VR methodology in an uncertain environment.

Expert Review and Consensus on the Treat-to-Target Management of Hereditary Angioedema: From Scientific Evidence to Clinical Practice

Background: Hereditary angioedema with C1 inhibitor deficiency (HAE-C1INH) is a rare disease characterized by swelling episodes. It affects quality of life (QOL) and can be fatal when the upper airways are involved. Treatment is individualized, with therapeutic options including on-demand treatment (ODT) and short- and long-term prophylaxis (STP, LTP). However, available guidelines are not always clear about the selection of treatment, the goals of treatment, or how achievement of these goals is assessed. Objective: To review available evidence for the management of HAE-C1INH and build a Spanish expert consensus to steer management towards a treat-to-target approach, while addressing some of the less clear aspects of the Spanish guidelines. Methods: We reviewed the literature on the treat-to-target management of HAE-C1INH, focusing on treatment selection and goals and the tools available to assess whether the goals have been achieved. We discussed the literature based on clinical experience and drew up 45 statements on undefined management aspects. A panel of 53 HAE experts validated the statements through a 2-round Delphi process. Results: The goals for ODT and STP are to minimize the morbidity and mortality of attacks and to prevent attacks caused by known triggers, respectively, while the main goal of LTP is to decrease the rate, severity, and duration of attacks. Furthermore, when prescribing, clinicians should consider the reduction in adverse effects, while increasing patient QOL and satisfaction. Appropriate instruments for assessing achievement of treatment goals are also indicated.Conclusions: We provide recommendations on previously unclear aspects of HAE-C1INH management with ODT, STP, and LTP, focusing on clinical and patient-oriented goals (AU)

Endoscopic submucosal dissection for superficial gastric neoplasias in two referral hospitals in Brazil: Can the Japanese and South Korean results be equaled?

INTRODUCTION AND AIMS: Endoscopic submucosal dissection (ESD) in the treatment of superficial neoplasias of the gastrointestinal tract is currently one of the greatest advances in therapeutic endoscopy. Due to its high technical complexity, it is not yet a routine procedure in Latin America. The aim of the present study was to present the experience in Brazil with ESD in superficial gastric neoplasias, based on training received from Japanese experts. MATERIALS AND METHODS: A retrospective study was conducted, in which information was prospectively collected from a database that included all patients that underwent ESD due to superficial gastric neoplasias at two endoscopy referral centers in Brazil, within the time frame of June 2008 to June 2019. En bloc, complete, and curative resection rates were calculated, along with the local recurrence rate and adverse events. RESULTS: A total of 103 ESDs for superficial gastric neoplasias were performed during the study period. Eighty of those patients (77.6%) presented with early malignant gastric neoplasias or premalignant lesions (adenocarcinoma: 52.5%, high-grade dysplasia: 27.5%, low-grade dysplasia: 16.3%, and neuroendocrine tumors: 3.8%). Overall en bloc and complete resection rates for the superficial gastric neoplasias were 96.3% and 92.5%, respectively, whereas the curative resection rate based on expanded criteria was 76%. CONCLUSIONS: ESD for the treatment of superficial gastric neoplasias is a safe and effective therapeutic modality in Latin America, with results similar to those shown in the most representative Japanese studies.

Field performance of sterile male mosquitoes released from an uncrewed aerial vehicle.

Genetic control methods of mosquito vectors of malaria, dengue, yellow fever, and Zika are becoming increasingly popular due to the limitations of other techniques such as the use of insecticides. The sterile insect technique is an effective genetic control method to manage insect populations. However, it is crucial to release sterile mosquitoes by air to ensure homogeneous coverage, especially in large areas. Here, we report a fully automated adult mosquito release system operated from an uncrewed aerial vehicle or drone. Our system, developed and tested in Brazil, enabled a homogeneous dispersal of sterile male Aedes aegypti while maintaining their quality, leading to a homogeneous sterile-to-wild male ratio due to their aggregation in the same sites. Our results indicate that the released sterile males were able to compete with the wild males in mating with the wild females; thus, the sterile males were able to induce sterility in the native female population. The use of drones to implement the sterile insect technique will lead to improvements in areal coverage and savings in operational costs due to the requirement of fewer release sites and field staff.

Anti-inflammatory and antinociceptive effects of the isatin derivative (Z)-2-(5-chloro-2-oxoindolin-3-ylidene)-N-phenyl-hydrazinecarbothioamide in mice.

Several isatin derivatives have shown important biological activities, which have attracted interest from researchers. For this reason, the present study aimed to evaluate the anti-inflammatory and antinociceptive effects of the isatin derivative (Z)-2-(5-chloro-2-oxoindolin-3-ylidene)-N-phenyl-hydrazinecarbothioamide (COPHCT) in mice. Three doses of this compound were tested: 1.0, 2.5, and 5.0 mg/kg. The anti-inflammatory activity was assessed using the carrageenan-induced paw edema model and the zymosan-induced air pouch model. The evaluation of the antinociceptive effect was performed through the formalin test and the acetic acid-induced abdominal writhing test. The paw edema assay demonstrated that all doses of the compound showed a significant reduction of the edema in the second hour evaluated, but a better response was observed in the fourth hour. The zymosan-induced air pouch model indicated that the compound, in all doses, significantly reduced leukocyte migration and total protein concentration levels. In the formalin test, the doses 1.0, 2.5, and 5.0 mg/kg of COPHCT showed activity only in the second phase, with reduction in paw pain time of 73.61, 79.46, and 73.85%, respectively. The number of abdominal writhings decreased with the increasing dose, but only 5.0 mg/kg COPHCT exhibited a significant response, with a reduction of 24.88%. These results demonstrated the ability of this compound to interfere in the anti-inflammatory activity of edema, vascular permeability, and cell migration. In addition, its possible antinociceptive effect may be related to the dose used.

Chlorophyll treatment combined with photostimulation increases glycolysis and decreases oxidative stress in the liver of type 1 diabetic rats

Photodynamic therapy (PDT) promotes cell death, and it has been successfully employed as a treatment resource for neuropathic complications of diabetes mellitus (T1DM) and hepatocellular carcinoma. The liver is the major organ involved in the regulation of energy homeostasis, and in pathological conditions such as T1DM, changes in liver metabolic pathways result in hyperglycemia, which is associated with multiple organic dysfunctions. In this context, it has been suggested that chlorophyll-a and its derivatives have anti-diabetic actions, such as reducing hyperglycemia, hyperinsulinemia, and hypertriglyceridemia, but these effects have not yet been proven. Thus, the biological action of PDT with chlorophyll-a on hepatic parameters related to energy metabolism and oxidative stress in T1DM Wistar rats was investigated. Evaluation of the acute effects of this pigment was performed by incubation of isolated hepatocytes with chlorophyll-a and the chronic effects were evaluated by oral treatment with chlorophyll-based extract, with post-analysis of the intact liver by in situ perfusion. In both experimental protocols, chlorophyll-a decreased hepatic glucose release and glycogenolysis rate and stimulated the glycolytic pathway in DM/PDT. In addition, there was a reduction in hepatic oxidative stress, noticeable by decreased lipoperoxidation, reactive oxygen species, and carbonylated proteins in livers of chlorophyll-treated T1DM rats. These are indicators of the potential capacity of chlorophyll-a in improving the status of the diabetic liver.

Chlorophyll treatment combined with photostimulation increases glycolysis and decreases oxidative stress in the liver of type 1 diabetic rats.

Photodynamic therapy (PDT) promotes cell death, and it has been successfully employed as a treatment resource for neuropathic complications of diabetes mellitus (T1DM) and hepatocellular carcinoma. The liver is the major organ involved in the regulation of energy homeostasis, and in pathological conditions such as T1DM, changes in liver metabolic pathways result in hyperglycemia, which is associated with multiple organic dysfunctions. In this context, it has been suggested that chlorophyll-a and its derivatives have anti-diabetic actions, such as reducing hyperglycemia, hyperinsulinemia, and hypertriglyceridemia, but these effects have not yet been proven. Thus, the biological action of PDT with chlorophyll-a on hepatic parameters related to energy metabolism and oxidative stress in T1DM Wistar rats was investigated. Evaluation of the acute effects of this pigment was performed by incubation of isolated hepatocytes with chlorophyll-a and the chronic effects were evaluated by oral treatment with chlorophyll-based extract, with post-analysis of the intact liver by in situ perfusion. In both experimental protocols, chlorophyll-a decreased hepatic glucose release and glycogenolysis rate and stimulated the glycolytic pathway in DM/PDT. In addition, there was a reduction in hepatic oxidative stress, noticeable by decreased lipoperoxidation, reactive oxygen species, and carbonylated proteins in livers of chlorophyll-treated T1DM rats. These are indicators of the potential capacity of chlorophyll-a in improving the status of the diabetic liver.

Anti-inflammatory and antinociceptive effects of the isatin derivative (Z)-2-(5-chloro-2-oxoindolin-3-ylidene)-N-phenyl-hydrazinecarbothioamide in mice

Several isatin derivatives have shown important biological activities, which have attracted interest from researchers. For this reason, the present study aimed to evaluate the anti-inflammatory and antinociceptive effects of the isatin derivative (Z)-2-(5-chloro-2-oxoindolin-3-ylidene)-N-phenyl-hydrazinecarbothioamide (COPHCT) in mice. Three doses of this compound were tested: 1.0, 2.5, and 5.0 mg/kg. The anti-inflammatory activity was assessed using the carrageenan-induced paw edema model and the zymosan-induced air pouch model. The evaluation of the antinociceptive effect was performed through the formalin test and the acetic acid-induced abdominal writhing test. The paw edema assay demonstrated that all doses of the compound showed a significant reduction of the edema in the second hour evaluated, but a better response was observed in the fourth hour. The zymosan-induced air pouch model indicated that the compound, in all doses, significantly reduced leukocyte migration and total protein concentration levels. In the formalin test, the doses 1.0, 2.5, and 5.0 mg/kg of COPHCT showed activity only in the second phase, with reduction in paw pain time of 73.61, 79.46, and 73.85%, respectively. The number of abdominal writhings decreased with the increasing dose, but only 5.0 mg/kg COPHCT exhibited a significant response, with a reduction of 24.88%. These results demonstrated the ability of this compound to interfere in the anti-inflammatory activity of edema, vascular permeability, and cell migration. In addition, its possible antinociceptive effect may be related to the dose used.

Pros and cons of insulin administration on liver glucose metabolism in strength-trained healthy mice.

Non-diabetic individuals use hormones like insulin to improve muscle strength and performance. However, as insulin also leads the liver and the adipose tissue to an anabolic state, the purpose of this study was to investigate the effects of insulin on liver metabolism in trained non-diabetic Swiss mice. The mice were divided into four groups: sedentary treated with saline (SS) or insulin (SI) and trained treated with saline (TS) or insulin (TI). Training was made in a vertical stair, at 90% of the maximum load, three times per week. Insulin (0.3 U/kg body weight) or saline were given intraperitoneally five times per week. After eight weeks, tissue and blood were collected and in situ liver perfusion with glycerol+lactate or alanine+glutamine (4 mM each) was carried out. The trained animals increased their muscle strength (+100%) and decreased body weight gain (-11%), subcutaneous fat (-42%), mesenteric fat (-45%), and peritoneal adipocyte size (-33%) compared with the sedentary groups. Insulin prevented the adipose effects of training (TI). The gastrocnemius muscle had greater density of muscle fibers (+60%) and less connective tissue in the trained groups. Liver glycogen was increased by insulin (SI +40% and TI +117%), as well as liver basal glucose release (TI +40%). Lactate and pyruvate release were reduced to a half by training. The greater gluconeogenesis from alanine+glutamine induced by training (TS +50%) was reversed by insulin (TI). Insulin administration had no additional effect on muscle strength and reversed some of the lipolytic and gluconeogenic effects of the resistance training. Therefore, insulin administration does not complement training in improving liver glucose metabolism.

Pros and cons of insulin administration on liver glucose metabolism in strength-trained healthy mice

Non-diabetic individuals use hormones like insulin to improve muscle strength and performance. However, as insulin also leads the liver and the adipose tissue to an anabolic state, the purpose of this study was to investigate the effects of insulin on liver metabolism in trained non-diabetic Swiss mice. The mice were divided into four groups: sedentary treated with saline (SS) or insulin (SI) and trained treated with saline (TS) or insulin (TI). Training was made in a vertical stair, at 90% of the maximum load, three times per week. Insulin (0.3 U/kg body weight) or saline were given intraperitoneally five times per week. After eight weeks, tissue and blood were collected and in situ liver perfusion with glycerol+lactate or alanine+glutamine (4 mM each) was carried out. The trained animals increased their muscle strength (+100%) and decreased body weight gain (-11%), subcutaneous fat (-42%), mesenteric fat (-45%), and peritoneal adipocyte size (-33%) compared with the sedentary groups. Insulin prevented the adipose effects of training (TI). The gastrocnemius muscle had greater density of muscle fibers (+60%) and less connective tissue in the trained groups. Liver glycogen was increased by insulin (SI +40% and TI +117%), as well as liver basal glucose release (TI +40%). Lactate and pyruvate release were reduced to a half by training. The greater gluconeogenesis from alanine+glutamine induced by training (TS +50%) was reversed by insulin (TI). Insulin administration had no additional effect on muscle strength and reversed some of the lipolytic and gluconeogenic effects of the resistance training. Therefore, insulin administration does not complement training in improving liver glucose metabolism.

Effects of nanoparticles of hydroxy-aluminum phthalocyanine on markers of liver injury and glucose metabolism in diabetic mice

Photodynamic therapy, by reducing pain and inflammation and promoting the proliferation of healthy cells, can be used to treat recurrent lesions, such as diabetic foot ulcers. Studies using the photosensitizer phthalocyanine, together with the nanostructured copolymeric matrix of Pluronic® and Carbopol® for the treatment of diabetic foot ulcers and leishmaniosis lesions, are showing promising outcomes. Despite their topical or subcutaneous administration, these molecules are absorbed and their systemic effects are unknown. Therefore, we investigated the effect of the subcutaneous administration of the hydroxy-aluminum phthalocyanine hydrogel without illumination on systemic parameters, markers of liver injury, and liver energy metabolism in type 1 diabetic Swiss mice. Both the hydrogel and the different doses of phthalocyanine changed the levels of injury markers and the liver glucose release, sometimes aggravating the alterations caused by the diabetic condition itself. However, the dose of 2.23 µg/mL caused less marked plasmatic and metabolic changes and did not change glucose tolerance or insulin sensitivity of the diabetic mice. These results are indicative that the use of hydroxy-aluminum phthalocyanine hydrogel for the treatment of cutaneous ulcers in diabetic patients is systemically safe.

Effects of nanoparticles of hydroxy-aluminum phthalocyanine on markers of liver injury and glucose metabolism in diabetic mice.

Photodynamic therapy, by reducing pain and inflammation and promoting the proliferation of healthy cells, can be used to treat recurrent lesions, such as diabetic foot ulcers. Studies using the photosensitizer phthalocyanine, together with the nanostructured copolymeric matrix of Pluronic® and Carbopol® for the treatment of diabetic foot ulcers and leishmaniosis lesions, are showing promising outcomes. Despite their topical or subcutaneous administration, these molecules are absorbed and their systemic effects are unknown. Therefore, we investigated the effect of the subcutaneous administration of the hydroxy-aluminum phthalocyanine hydrogel without illumination on systemic parameters, markers of liver injury, and liver energy metabolism in type 1 diabetic Swiss mice. Both the hydrogel and the different doses of phthalocyanine changed the levels of injury markers and the liver glucose release, sometimes aggravating the alterations caused by the diabetic condition itself. However, the dose of 2.23 µg/mL caused less marked plasmatic and metabolic changes and did not change glucose tolerance or insulin sensitivity of the diabetic mice. These results are indicative that the use of hydroxy-aluminum phthalocyanine hydrogel for the treatment of cutaneous ulcers in diabetic patients is systemically safe.