In health and illness: does taste remain consistent? Exploring the influence of inflammation on taste perception through a systematic review and meta-analysis.

OBJECTIVE: Dysgeusia is characterized by a loss of taste perception, leading to malnutrition. This situation affects inflammatory conditions such as respiratory and neurological conditions, obesity, cancer, chemotherapy, aging, and many others. To date, there is not much information on the prevalence and risk of dysgeusia in an inflammatory condition; also, it is unclear which flavor is altered. MATERIALS AND METHODS: We systematically searched three databases from January 2018 to January 2023. Participants were children, adults, or elderly persons with an inflammatory condition and evaluated taste loss. A random effects model was used for statistical analysis to calculate the pooled odds ratio with its corresponding 95.0% confidence interval to estimate the probability of taste alteration (dysgeusia) in an inflammatory condition. RESULTS: The data allowed us to conduct a systematic review, including 63 original articles and 15 studies to perform the meta-analysis. The meta-analysis indicated a heterogenicity of 84.7% with an odds ratio of 3.25 (2.66-3.96), indicating a significant risk of Alzheimer's disease, SARS-CoV-2, chemotherapy, and rhinosinusitis. CONCLUSIONS: Inflammatory conditions and taste alterations are linked. Dysgeusia is associated with a higher risk of malnutrition and poorer general health status, especially in vulnerable populations.

Chitosan derivatives as nanocarriers for hLDHA inhibitors delivery to hepatic cells: A selective strategy for targeting primary hyperoxaluria diseases.

Primary hyperoxalurias (PHs) are a group of inherited alterations of the hepatic glyoxylate metabolism that result in an excess of oxalate production by the oxidation of glyoxylate by the human lactate dehydrogenase A enzyme (hLDHA). The selective liver inhibition of this enzyme is one of the therapeutic strategies followed in the treatment of this disease. Even though several efforts have been recently performed using gene silencing by the RNA interference approach, small-molecule inhibitors that selectively reach hepatocytes are preferred since they present the advantages of a lower production cost and better pharmacological properties. In that sense, the design, synthesis, and physicochemical characterization by NMR, FTIR, DLS and TEM of two nanocarriers based on chitosan conjugates (1, non-redox-sensitive; 2, redox-sensitive) have been performed to (i) achieve the selective transport of hLDHA inhibitors into hepatocytes and (ii) their disruption once they reach the hepatocytes cytosol. Polymer 2 self-assembled into micelles in water and showed high drug loadings (19.8-24.5 %) and encapsulation efficiencies (31.9-40.8%) for the hLDHA inhibitors (I-III) tested. The non-redox-sensitive micelle 1 remained stable under different glutathione (GSH) concentrations (10 µM and 10 mM), and just a residual release of the inhibitor encapsulated was observed (less than 10 %). On the other hand, micelle 2 was sufficiently stable under in vitro physiological conditions (10 µM, GSH) but it quickly disassembled under the simulated reducing conditions present inside hepatocytes (10 mM GSH), achieving a 60 % release of the hLDHA inhibitor encapsulated after 24 h, confirming the responsiveness of the developed carrier to the high levels of intracellular GSH.

Extended totally extraperitoneal (eTEP) treatment for lateral primary and incisional hernias. New approach to old problems.

PURPOSE: To describe the eTEP approach for treating lateral primary and incisional hernia and show its results in a prospective series of cases. METHODS: A descriptive prospective study with patients treated surgically for lateral hernias using eTEP approach. Every patient was operated by the same surgeon from November 2018 to December 2021. Inclusion criteria were primary and incisional hernia, lateral and W1 and W2 sized using the EHS classification. Exclusion criteria were W3 hernia, loss of domain, need to remove previous mesh, dystrophic or ulcerative skin, history of previous complex surgery. Details of the surgical technique are described. RESULTS: 34 patients were operated. Median age was 65 years old and BMI, 29.9 (22.1-47.1). There were several locations being the most frequent L3 in 18 patients. The median length was 41 mm (10-129) and width, 44 mm (10-97). The median of defect-mesh ratio was 5.05 (0.9-447.64). TAR was practised in 21 patients (61.8%). Only one patient suffered a clinically relevant complication, being a hematoma (Dindo-Clavien II). 50% of patients were operated in ambulatory surgery. After a median follow-up of 13.5 months, only one recurrence has been reported (2.9%). CONCLUSION: eTEP to treat lateral hernias is feasible and reproducible showing good results in terms of hernia recurrence and complications. A further prospective randomized clinical trial is needed to support these results.

Body Mass Index impact on Extended Total Extraperitoneal Ventral Hernia Repair: a comparative study.

PURPOSE: Obesity is a risk factor for developing abdominal wall hernias and is associated with major postoperative complications, such as surgical site infection, delayed wound healing and recurrent hernia. Therefore, treating incisional hernia in this patient subgroup is a challenge. METHODS: We conducted a comparative, prospective study on patients who underwent primary ventral hernia surgery or incisional hernia surgery through the extended totally extraperitoneal pathway, with body mass indices (BMIs) ≤ 30 (no obesity) and BMI > 30 (with obesity). We collected demographic data, preoperative and intraoperative variables, complication and recurrence rate, hospital stay and follow-up as postoperative data. RESULTS: From May 2018 to December 2020, 74 patients underwent this surgery, 38 patients without obesity and 36 with obesity. The median area of the hernia defect measured by CT was 57 cm2 and 93 cm2 in patients without and with obesity, respectively (p = 0.012). The median follow-up was 16 months. One patient without obesity experienced some postoperative complication compared with four patients with obesity (p > 0.05). No patient without obesity had recurrent hernia compared with two patients with obesity (p > 0.05). CONCLUSIONS: There were statistically significant differences between patients with and without obesity in the size of the hernia defect. However, there were no significant differences in terms of complications, hospital stay, postoperative pain or relapses. Therefore, the minimally invasive completely extraperitoneal approach for patients with obesity appears to be a safe procedure despite our study limitations. Studies with longer follow-ups and a greater number of patients are needed.

(-)­Oleocanthal inhibits proliferation and migration by modulating Ca2+ entry through TRPC6 in breast cancer cells.

Triple negative breast cancer is an aggressive type of cancer that does not respond to hormonal therapy and current therapeutic strategies are accompanied by side effects due to cytotoxic actions on normal tissues. Therefore, there is a need for the identification of anti-cancer compounds with negligible effects on non-tumoral cells. Here we show that (-)­oleocanthal (OLCT), a phenolic compound isolated from olive oil, selectively impairs MDA-MB-231 cell proliferation and viability without affecting the ability of non-tumoral MCF10A cells to proliferate or their viability. Similarly, OLCT selectively impairs the ability of MDA-MB-231 cells to migrate while the ability of MCF10A to migrate was unaffected. The effect of OLCT was not exclusive for triple negative breast cancer cells as we found that OLCT also attenuate cell viability and proliferation of MCF7 cells. Our results indicate that OLCT is unable to induce Ca2+ mobilization in non-tumoral cells. By contrast, OLCT induces Ca2+ entry in MCF7 and MDA-MB-231 cells, which is impaired by TRPC6 expression silencing. We have found that MDA-MB-231 and MCF7 cells overexpress the channel TRPC6 as compared to non-tumoral MCF10A and treatment with OLCT for 24-72 h downregulates TRPC6 expression in MDA-MB-231 cells. These findings indicate that OLCT impairs the ability of breast cancer cells to proliferate and migrate via downregulation of TRPC6 channel expression while having no effect on the biology of non-tumoral breast cells.

Optimization and prediction of the electron-nuclear dipolar and scalar interaction in 1H and 13C liquid state dynamic nuclear polarization.

During the last 10-15 years, dynamic nuclear polarization (DNP) has evolved as a powerful tool for hyperpolarization of NMR and MRI nuclides. However, it is not as well appreciated that solution-state dynamic nuclear polarization is a powerful approach to study intermolecular interactions in solution. For solutions and fluids, the 1H nuclide is usually dominated by an Overhauser dipolar enhancement and can be significantly increased by decreasing the correlation time (τc) of the substrate/nitroxide interaction by utilizing supercritical fluids (SF CO2). For molecules containing the ubiquitous 13C nuclide, the Overhauser enhancement is usually a profile of both scalar and dipolar interactions. For carbon atoms without an attached hydrogen, a dipolar enhancement usually dominates as we illustrate for sp2 hybridized carbons in the fullerenes, C60 and C70. However, the scalar interaction is dependent on a Fermi contact interaction which does not have the magnetic field dependence inherent in the dipolar interaction. For a comprehensive range of molecular systems we show that molecules that exhibit weakly acidic complexation interaction(s) with nitroxides provide corresponding large scalar enhancements. For the first time, we report that sp hybridized (H-C) alkyne systems, for example, the phenylacetylene-nitroxide system exhibit very large scalar dominated enhancements. Finally, we demonstrate for a wide range of molecular systems that the Fermi contact interaction can be computationally predicted via electron-nuclear hyperfine coupling and correlated with experimental 13C DNP enhancements.

Parathyroid adenoma in third pharyngeal pouch cyst as a rare case of primary hyperparathyroidism.

The primitive thymus and inferior parathyroid derive from the third branchial cleft. During embryonic development, these structures descend, reaching their final localisation. Third branchial cleft anomalies present usually as a fistula, abscess or cyst. However, there are no reports on parathyroid adenomas in the literature other than as a morphological possibility. We describe the case of a 47-year-old man, who had been diagnosed with arterial hypertension and who presented with a cervical mass at the edge of the lower third of the sternocleidomastoid muscle. On ultrasonography, the mass had a cystic walled appearance. Laboratory analysis only revealed an intact parathyroid hormone level of 140.5 pg/ml. Sestamibi imaging showed a probable parathyroid adenoma in the anterior mediastinum. During surgery, a tract running from beyond the superior thyroid pedicle to the superior mediastinum was dissected and removed. In the inferior end of the tract, a brown mass was visible. Pathological examination revealed a thymus cyst surrounding a parathyroid adenoma. The primal alteration was the lack of division between the thymus and inferior parathyroid gland, and the prompt prevention of their development. In the case of our patient, a parathyroid adenoma had grown by chance.

Cinnamtannin B-1 from bay wood reduces abnormal intracellular Ca2+ homeostasis and platelet hyperaggregability in type 2 diabetes mellitus patients.

Type 2 diabetes mellitus induces a number of cardiovascular disorders, including platelet hyperactivity and hyperaggregability, which is associated to an increased oxidant production and abnormal cytosolic Ca2+ mobilization. In the present study, we have investigated the effect of cinnamtannin B-1 obtained from bay wood on oxidants production, Ca2+ mobilization and aggregation in platelets from type 2 diabetic donors. Pretreatment of platelets with cinnamtannin B-1 reversed the enhanced oxidants production and Ca2+ mobilization, including Ca2+ entry, evoked by thapsigargin plus ionomycin or thrombin, observed in platelets from diabetic subjects, so that in the presence of cinnamtannin B-1 Ca2+ entry was similar in platelets from healthy and diabetic subjects. In addition, cinnamtannin B-1 reduced thrombin-induced aggregation in platelets from type 2 diabetic subjects. We conclude that cinnamtannin B-1 exerts an effective antioxidant action in platelets from patients with type 2 diabetes mellitus and reverses the enhanced Ca2+ mobilization and hyperaggregability.

Cinnamtannin B-1 from bay wood exhibits antiapoptotic effects in human platelets.

Proanthocyanidins, such as cinnamtannin B-1, are polyphenolic compounds with antioxidant activity that induce apoptosis in a number of tumoral cells. We have now investigated the pro- or anti-apoptotic effects of cinnamtannin B-1 in human platelets. Platelet stimulation with thrombin induced cellular apoptosis, as detected by phosphatidylserine exposure and the activation of caspases-3 and -9. Pretreatment for 30 min with cinnamtannin B-1 impaired thrombin-induced apoptosis in platelets. Thrombin has been shown to induce H(2)O(2) generation in platelets, which induced similar apoptotic events than thrombin in these cells. Pretreatment with cinnamtannin B-1 reduced H(2)O(2)-induced phosphatidylserine exposure and caspase activation. Finally, platelet stimulation with thrombin induced translocation of caspases-3 and -9 to the cytoskeletal (Triton-insoluble) fraction, which is important for their activation and the development of apoptotic events. Pretreatment with cinnamtannin B-1 impaired translocation of caspases-3 and -9 to the cytoskeleton and, as a result, procaspases are accumulated in the Triton-soluble fraction. Our results provide evidence for the antiapoptotic actions of cinnamtannin B-1 in human platelets.