The prevalence of constipation at admission and after 1 week of palliative care: a multi-center study

Aim: To assess the prevalence and intensity of constipation in advanced-cancer patients referred to palliative care, and to assess changes after 1 week of specialist palliative care.

Methods: This was a prospective multi-center study in advanced patients for a period of 1 year. At admission (T0), age, gender, primary tumor, concomitant diseases, Karnofsky status, Palliative prognostic score (PaP), Edmonton Symptom Assessment scale (ESAS), Memorial Delirium Assessment Scale (MDAS), and bowel function index (BFI) were collected. In BFI, high values represent severe constipation. The use of medication was also recorded, as well as possible causes of constipation. The same parameters were recorded 1 week after admission for palliative care (T7).

Results: A total of 246 patients were screened for constipation. The mean BFI at T0 was 42.4 (SD?=?26.92). One hundred and sixty-three patients (66.3%) had a BFI >28. The mean BFI at T7 was 35.7 (SD?=?28.8), with a significant decrease from T0 to T7 (p?=?.000). A significant decrease of BFI in patients with a BFI >28 was reported (p?=?.000). In patients with a BFI ≤28 there was a significant worsening of constipation (p?=?.000). In patients with a BFI >28 at T0 there was a significant increase in the use of laxatives at T7 in comparison with patients having a BFI ≤28 (p?=?.002). In patients with a BFI ≤28 at T0, who had a significant worsening of BFI (Δ?>?12), the use of laxatives was significantly lower in comparison to patients who had a BFI >28 (p?=?.000). In the multivariate analysis, dehydration and the use of benzodiazepines were independently associated with higher BFI scores.

Conclusion: Constipation is present in approximately two-thirds of patients, and is principally associated with dehydration and the use of benzodiazepines. Patients with normal bowel function at initial assessment may see a worsening in their condition a week later due to lack of prevention or subsequent under-treatment.     

Regulation of thyroid sodium‐iodide symporter in different stages of goiter: Possible involvement of reactive oxygen species

Na⁺/I^? symporter (NIS) transports iodide into thyrocytes, a fundamental step for thyroid hormone biosynthesis. Our aim was to evaluate NIS regulation in different status of goitrogenesis and its underlying mechanisms. Wistar rats were treated with methimazole (MMI) for 5 and 21 days, to achieve different status of goiter. We then evaluated the effect of MMI removal for 1 day (R1d), after 5 (R1d‐5d) or 21 (R1d‐21d) days of MMI treatment. MMI increased thyroid weight, iodide uptake and in vitro TPO activity in a time‐dependent way. Although MMI removal evoked a rapid normalization of TPO activity in R1d‐5d, it was still high in R1d‐21d. On the other hand, iodide uptake was rapidly down‐regulated in R1d‐21d, but not in R1d‐5d, suggesting that the increased TPO activity in R1d‐21d led to increased intraglandular organified iodine (I‐X), which is known to inhibit iodide uptake. Since TGFβ has been shown to mediate some effects of I‐X, we evaluated TGFβ and TGFβ receptor mRNA levels, which were increased in R1d‐21d. Moreover, it has been demonstrated that TGFβ stimulates NOX4. Accordingly, our data revealed increased NOX4 expression and H₂O₂ generation in R1d‐21d. Finally, we evaluated the effect of H₂O₂ on NIS function and mRNA levels in PCCL3 thyroid cell line, which were reduced. Thus, the present study suggests that there is a relationship between the size of the goiter and NIS regulation and that the mechanism might involve I‐X, TGFβ, NOX4 and increased ROS production.     

Can lithium salts prevent depressive episodes in the real world?

To critically examine the effectiveness of lithium in preventing depressive symptoms (mixed and depressive episodes) in real life settings, taking into account adherence to drug treatment and its implications for the clinical costs of the disease. Overall, 72 patients with bipolar disorder initially treated with lithium carbonate were included and followed-up for 10 years. Patients were assessed every 8 weeks for morbidity and alcohol/drug consumption. Patients with good adherence to lithium had fewer episodes with depressive features than poor adherers (B?=?2.405, p?=?0.046) and also fewer manic and hypomanic episodes (B?=?2.572; p?<?0.001), after controlling for confounders. Time to relapse into a depressive or mixed episode and into a manic or hypomanic episode was shorter in patients with poor adherence. The costs of the 1.95?±?2.38 (mean?±?standard deviation) admissions of adherent patients through the 10 years of follow-up were €10,349, while the costs of the 6.25?±?4.92 admissions of non-adherent patients were €44,547. In clinical practice settings, long-term lithium salts seem to have a preventive effect on depressive symptoms.     

Effect of olive cultivar on bioaccessibility and antioxidant activity of phenolic fraction of virgin olive oil

Aim

This study aims to characterize the phenolic profile and antioxidant capacity of seven monovarietal virgin olive oils (VOOs) and evaluate their in vitro gastrointestinal stability.

Methods

‘Picual’, ‘Blanqueta’, ‘Sevillana’, ‘Habichuelero’, and ‘Chetoui’ olive cultivars were selected for VOO extraction. The oils were subjected to in vitro digestion. The recovery index (RI) of phenolic compounds after each digestion step and the bioaccessibility index (BI) were evaluated. In addition, the antioxidant activity of the bioaccessible fraction (BF) of VOOs was determined by DPPH, ABTS, and ORAC assays, as well as by studying the intracellular reactive oxygen species in Caco-2 cells.

Results

Differences were found in the composition of phenolic compounds in VOOs depending on cultivars. During the digestive process, important losses of phenolic compounds were observed between the buccal and duodenal steps, unlike HTy and Ty, which presented increased recovery due to the hydrolysis of secoiridoid derivatives. Differences in the bioaccessibility of phenolic compounds were found between varieties of VOOs. ‘Sevillana’ VOO had the highest total bioaccessibility (36%), followed by the ‘Picual’ (19%), ‘Chetoui’ (17%), ‘Habichuelero’ (10%), and ‘Blanqueta’ (8%) varieties. The BF of all the varieties of VOO showed similar radical ABTS scavenging capacity, ‘Chetoui’, and ‘Blanqueta’-BF having the highest radical DPPH scavenging capacity, and ‘Habichuelero’ and ‘Picual’-BF showing protective effects against the peroxyl radical measured by ORAC_FL assay. All VOO-BFs presented decreases in ROS levels in Caco-2 cells.

Conclusions

Our results suggest differences in the bioaccessibility of phenolics from diverse VOO varieties, which could lead to different biological properties. Therefore, this study represents a first step toward the development of novel dietary strategies focusing on the phenolic supplementation of different VOOs to preserve human health.

     

Agricultural Experiences Are Positively Associated With High School Students' Fruit and Vegetable Perceptions and Consumption

Objective

To examine the relationship between high school students' agricultural experiences and their (1) attitudes about consuming local fruits and vegetables, (2) willingness to try new fruits and vegetables, and (3) fruit and vegetable consumption.

Unobserved heterogeneity in work absence

Labour absenteeism may be detrimental to firms and society because of the economic costs, organizational problems and production cuts that it involves. Although involuntary absenteeism due to accident or illness that prevents workers from performing their work is unavoidable, avoidable voluntary absenteeism may also emerge due to asymmetric information given that neither employers nor doctors have perfect information about workers’ health status. Assuming that there is heterogeneity in individual’s behaviour and thus some workers are more likely to take sick leave than others due to differences in observable and unobservable characteristics, we specify a Finite Mixture Model to analyse sick leave days per year using a sample of employees from the 2014 European Health Survey in Spain. This specification accounts for unobserved heterogeneity in a discrete way assuming that there are two types of workers even though the data do not allow us to identify which group any individual belongs to. Our results reveal that, although health indicators have the greatest impact on the proportional change in days of absenteeism, there is heterogeneity in sick leave decisions and individual and job characteristics have different effect on the absenteeism of each group.     

Selective induction of apoptosis in MCF7 cancer-cell by targeted liposomes functionalised with mannose-6-phosphate

Liposomes are versatile platforms to carry anticancer drugs in targeted drug delivery; they can be surface modified by different strategies and, when coupled with targeting ligands, are able to increase cellular internalisation and organelle-specific drug delivery. An interesting strategy of antitumoral therapy could involve the use of lysosomotropic ligand-targeted liposomes loaded with molecules, which can induce lysosomal membrane permeabilization (LMP), leakage of cathepsins into the cytoplasm and subsequent apoptosis. We have previously demonstrated the ability of liposomes functionalised with a mannose-6-phosphate to reach lysosomes; in this research we compare the behaviour of M6P-modified and non-functionalised liposomes in MCF7 tumour cell and in HDF normal cells. With this aim, we first demonstrated by Western blotting the overexpression of mannose-6-phosphate/insulin-like growth factor (M6P/IGF-II) receptor in MCF7. Then, we prepared calcein-loaded liposomes and we revealed the increased uptake of M6P-functionalised liposomes in MCF7 cells respect to HDF cells by flow cytometry analysis. Finally, we loaded functionalised and not functionalised liposomes with N-hexanoyl-d-erythro-sphingosine (C6Cer), able to initiate LMP-induced apoptosis; after having studied the stability of both vesicles in the presence of serum by Dynamic Light Scattering and Spectrophotometric turbidity measurements, we showed that ceramide-loaded M6P-liposomes significantly increased apoptosis in MCF7 with respect to HDF cells.     

HIV cure: global overview of bNAbs’ patents and related scientific publications

Introduction: This article provides a global overview of patent deposits for broadly neutralizing antibodies (bNAbs), which have emerged as a key strategy for HIV cure and future HIV vaccines. Scientific and technological barriers to the discovery of an effective HIV vaccine in the last 40 years have raised concerns on the potential for relevant advances in this area. Nevertheless, recent breakthrough studies have identified novel immune pathways for new innovative HIV vaccine and HIV cure strategies.

Areas covered: In our patent study, we have identified in a global scale, in the last decade, a sharp increase in the number of bNAbs’ patent deposits related to HIV prevention and treatment strategies, reaching 90 bNAbs in 2017, protected by 184 different patent deposits. Refining our patent search to the different stages of bNAbs’ development has also allowed us to identify 12 of them already at clinical stage of research (VRC01, 10E8, 3BNC117, 10-1074, 2G12, 2F5, KD-247, 4E10, PG9, PGDM1400, PGT121, and VRC07). We describe these recent breakthroughs and discuss the prospects and limitations of these novel strategies.

Expert opinion: Our results indicate the intellectual property outcomes of a scientific revolution in this field, expressing innovative modifications in antibodies to increase their potency and half-life, which have resulted in extremely potent antibodies that could provide novel preventive and therapeutic HIV strategies.     

Patents related to the treatment and diagnosis of bruxism

Introduction: Bruxism is among the most chronic dental problems worldwide, and its perception may increase indicatively the condition of people’s health, avoiding future health problems. Technologic solutions have improved considerably owing to new diagnostic and treatment technologies and their automation. This review aims to assess therapeutic methods for bruxism through analysis of patent applications spanning recent decades.

Areas covered: Patent families of bruxism, and products available on the market. Data were obtained through Questel Orbit from the European Patent Office on a worldwide basis using Cooperative Patent Classification (CPC), analyzing 134 patent families. The products on the market were mapped and classified as used for diagnosis, treatment, or both.

Expert opinion: This technological prospect has shown that the technological field of bruxism is growing toward smaller, automated devices; there is still no predominant owner of the technologies. Products are expected to provide home use with a high degree of reliability and specificity, using the Internet of Things (telemedicine associated with industry 4.0) and enabling real-time diagnosis.