Polyphenolic profile, processing impact, and bioaccessibility of apple fermented products.

Health-promoting foods have become increasingly popular due to intensified consumer interest and awareness of illnesses. There is a global market for apple fruits, which are affordable, nutritious, tasty, and produced in large quantities for direct consumption as well as food processing to make derived products. The food matrix of apples is suitable for fermentation, besides containing a high amount of phenolics and polyphenols. Fermentation of apples is one of the most common methods of preserving apple fruit and its byproducts. With different fermentation techniques, apple fruit can be used to make a wide range of products, such as fermented apple juice, cider, liqueurs, apple cider, apple vinegar and fermented apple solids, because it is not only a low-cost and simple method of processing the fruit, but it can also sometimes increase the bioavailability of nutrients and the levels of components that can improve health and sensory quality. To understand the health benefits of food products and how the fermentation process impacts polyphenols, it is also crucial to observe the effects of digestion on polyphenol bioaccessibility. Polyphenolic profile changes can be observed via both in vitro and in vivo digestion methods; however, in vitro digestion methods have the advantage of observing every step of gastrointestinal track effects and have less cost as well. In this review, the polyphenolic profile, processing impact, and bioaccessibility of apple-fermented products is assessed, with most available studies showing polyphenol profiles and bioaccessibility in apple varieties and fermented apple products.

Seaweed polysaccharides: Emerging extraction technologies, chemical modifications and bioactive properties.

Nowadays, consumers are increasingly aware of the relationship between diet and health, showing a greater preference of products from natural origin. In the last decade, seaweeds have outlined as one of the natural sources with more potential to obtain bioactive carbohydrates. Numerous seaweed polysaccharides have aroused the interest of the scientific community, due to their biological activities and their high potential on biomedical, functional food and technological applications. To obtain polysaccharides from seaweeds, it is necessary to find methodologies that improve both yield and quality and that they are profitable. Nowadays, environmentally friendly extraction technologies are a viable alternative to conventional methods for obtaining these products, providing several advantages like reduced number of solvents, energy and time. On the other hand, chemical modification of their structure is a useful approach to improve their solubility and biological properties, and thus enhance the extent of their potential applications since some uses of polysaccharides are still limited. The present review aimed to compile current information about the most relevant seaweed polysaccharides, available extraction and modification methods, as well as a summary of their biological activities, to evaluate knowledge gaps and future trends for the industrial applications of these compounds.Key teaching pointsStructure and biological functions of main seaweed polysaccharides.Emerging extraction methods for sulfate polysaccharides.Chemical modification of seaweeds polysaccharides.Potential industrial applications of seaweed polysaccharides.Biological activities, knowledge gaps and future trends of seaweed polysaccharides.

Biological properties and potential of compounds extracted from red seaweeds.

Macroalgae have been recently used for different applications in the food, cosmetic and pharmaceutical industry since they do not compete for land and freshwater against other resources. Moreover, they have been highlighted as a potential source of bioactive compounds. Red algae (Rhodophyta) are the largest group of seaweeds, including around 6000 different species, thus it can be hypothesized that they are a potential source of bioactive compounds. Sulfated polysaccharides, mainly agar and carrageenans, are the most relevant and exploited compounds of red algae. Other potential molecules are essential fatty acids, phycobiliproteins, vitamins, minerals, and other secondary metabolites. All these compounds have been demonstrated to exert several biological activities, among which antioxidant, anti-inflammatory, antitumor, and antimicrobial properties can be highlighted. Nevertheless, these properties need to be further tested on in vivo experiments and go in-depth in the study of the mechanism of action of the specific molecules and the understanding of the structure-activity relation. At last, the extraction technologies are essential for the correct isolation of the molecules, in a cost-effective way, to facilitate the scale-up of the processes and their further application by the industry. This manuscript is aimed at describing the fundamental composition of red algae and their most studied biological properties to pave the way to the utilization of this underused resource.

Solutions for the sustainability of the food production and consumption system.

Due to the increasing population, there is high concern about whether the current food system will be able to provide enough healthy food for 10 billion people by 2050. The general opinion is that it is possible to feed this population, but the food system requires major transformations on behalf of promoting sustainability, reducing food waste and stimulating a change toward diets healthy for humans and also sustainable for the planet. This article will review some detected problems in food production and consumption. In food production, current problems like destruction of land ecosystems, overfishing or generation of high amounts of residues stand out. Some solutions have been described, such as implement the agroecology, improve productivity of aquaculture or re-valorization of by-products. In food consumption, the main problems are the food fraud and the unhealthy dietary patters, whose main solutions are the standardization along food chain and education on healthy lifestyles. Concluding, food system should change toward more sustainable practices and behaviors in other to ensure the subsistence of the present and the future generations.

Risk of a Second Skin Cancer in a Cohort of Patients With Nonmelanoma Skin Cancer -Basal Cell Carcinoma or Squamous Cell Carcinoma-Treated With Mohs Micrographic Surgery: A National Prospective Cohort Study. / Riesgo de aparición de segundas neoplasias cutáneas en una cohorte de pacientes diagnosticados de carcinoma queratinocítico (carcinoma basocelular y carcinoma epidermoide) tratados con cirugía de Mohs. Estudio de cohortes prospectivo nacional.

OBJECTIVE: Patients with nonmelanoma skin cancer (NMSC)-ie, basal cell carcinoma (BCC) or squamous cell carcinoma (SCC)-have an increased risk of developing a second skin cancer. The aim of this study was to describe the frequency, incidence per 1000 person-years, and predictors of a second skin cancer in a cohort of patients with NMSC treated with Mohs micrographic surgery (MMS). MATERIAL AND METHODS: Prospective study of a national cohort of patients with NMSC who underwent MMS at 22 Spanish hospitals between July 2013 and February 2020; case data were recorded in the REGESMOHS registry. The study variables included demographic characteristics, frequency and incidence per 1000 person-years of second skin cancers diagnosed during the study period, and risk factors identified using mixed-effects logistic regression. RESULTS: We analyzed data for 4768 patients who underwent MMS; 4397 (92%) had BCC and 371 (8%) had SCC. Mean follow-up was 2.4 years. Overall, 1201 patients (25%) developed a second skin cancer during follow-up; 1013 of the tumors were BCCs (21%), 154 were SCCs (3%), and 20 were melanomas (0.4%). The incidence was 107 per 1000 person-years (95% CI, 101-113) for any cancer, 90 per 1000 person-years (95% CI, 85-96) for BCC, 14 (95% CI, 12-16) per 1000 person-years for SCC, and 2 (95% CI, 1-3) per 1000 person-years for melanoma. More men than women developed a subsequent skin cancer (738 [61%] vs 463 [39%]). The main risk factors were a history of multiple tumors before diagnosis (relative risk [RR], 4.6; 95% CI, 2.9-7.1), immunosuppression (RR, 2.1; 95% CI, 1.4-3.1), and male sex (RR, 1.6; 95% CI, 1.4-1.9). CONCLUSION: Patients have an increased risk of developing a second tumor after MMS treatment of NMSC. Risk factors are a history of multiple tumors at diagnosis, immunosuppression, and male sex.

Effectiveness of an intervention in multicomponent exercise in primary care to improve frailty parameters in patients over 70 years of age (MEFAP-project), a randomised clinical trial: rationale and study design.

BACKGROUND: Physical activity may reverse frailty in the elderly, but we encounter barriers to the implementation of exercise programs in this population. Our main aim is to evaluate the effect of a multicomponent physical activity program, versus regular medical practice, on reverting pre-frailty status among the elderly, 12 months post-intervention. METHODS: Randomized parallel group multicenter clinical trial located in primary care setting, among non-dependent and pre-frail patients > 70 years old, including 190 patients (95 intervention, 95 control group). INTERVENTION: Multicomponent physical activity program (MEFAP, for its acronym in Spanish) with twelve 1.5 h-weekly sessions comprised of: 1. Informative session; 2. Exercises for improving aerobic resistance, muscle strength, propioception-balance and flexibility; and 3. Handing out of at-home exercise chart (twice/week). Main variable: pre-frailty according to the Fried phenotype. Secondary variables: sociodemographic, clinical and functional variables; exercise program adherence, patient satisfaction with the program and quality of life. We will perform an intention-to-treat analysis by comparing the retrogression from pre-frailty (1 or 2 Fried criteria) to robust status (0 Fried criteria) by the end of the intervention, 6 months and 12 months post-intervention. The accumulated incidence in each group will be calculated, as well as the relative risk (RR) and the number needed to treat (NNT) with their corresponding 95% confidence intervals. Protocol was approved by the Ethics Committee Hospital la Paz. DISCUSSION: Within the context of regular clinical practice, our results will provide evidence regarding the effects of exercise interventions on frailty among pre-frail older adults, a key population given their significant potential for functional, physical, and mental health improvement. TRIAL REGISTRATION: NCT03568084 . Registered 26 June 2018. Date of enrollment of the first participant to the trial: July 2nd 2018.

Ultrasound as a Rapid and Low-Cost Extraction Procedure to Obtain Anthocyanin-Based Colorants from Prunus spinosa L. Fruit Epicarp: Comparative Study with Conventional Heat-Based Extraction.

An ultrasound rapid and low-cost procedure for anthocyanin-based colorants from Prunus spinosa L. fruit epicarp was developed, and the advantages were compared with conventional heat-based extraction. To obtain the conditions that maximize anthocyanins' extraction, a response surface methodology was applied using the variables of time, temperature, and ethanol content, in the case of heat extraction, whereas for ultrasound assisted extraction, temperature was replaced by ultrasound power. Two anthocyanin compounds were identified by HPLC-DAD-ESI/MS-namely, cyanidin 3-rutinoside and peonidin 3-rutinoside. The responses used were the extraction yield and the content of the identified anthocyanins. Ultrasound extraction was the most effective method at 5.00 ± 0.15 min, 400.00 ± 32.00 W, and 47.98% ± 2.88% of ethanol obtaining 68.60% ± 2.06% of extracted residue, with an anthocyanin content of 18.17 mg/g (extract-basis) and 11.76 mg/g (epicarp-basis). Overall, a viable green process was achieved that could be used to support pilot-scale studies for industrial production of anthocyanin-based colorants from P. spinosa fruit epicarp.

Mohs micrographic surgery in the elderly: comparison of tumours, surgery and first-year follow-up in patients younger and older than 80 years old in REGESMOHS.

BACKGROUND: The elderly population is increasing and more patients in this group undergo Mohs micrographic surgery (MMS). The few publications investigating MMS in elderly people conclude that it is a safe procedure; however, these are single-centre studies without a comparison group. OBJECTIVE: To compare the characteristics of patients, tumours, MMS and 1-year follow-up in patients younger than 80 years, with patients older than 80 years at the time of surgery. METHODS: Data was analysed from REGESMOHS, a prospective cohort study of patients treated with MMS. The participating centres were 19 Spanish hospitals where at least one MMS is performed per week. Data on characteristics of the patient, tumour and surgery were recorded. Follow-up data were collected from two visits; the first within 1 month postsurgery and the second within the first year. RESULTS: From July 2013 to October 2016, 2575 patients that underwent MMS were included in the registry. Of them, 1942 (75.4%) were aged <80 years and 633 (24.6%) were ≥80 years old. In the elderly, the tumour size was significantly higher with a higher proportion of squamous cell carcinoma. Regarding surgery, elderly more commonly had tumours with deeper invasion and required a higher number of Mohs surgery stages, leaving larger defects and requiring more time in the operating room. Despite this, the incidence of postoperative complications was the same in both groups (7%) and there were no significant differences in proportion of relapses in the first-year follow-up. CONCLUSION: The risk of short-term complications and relapses were similar in elderly and younger groups. MMS is a safe procedure in the elderly.

Mathematical models of cytotoxic effects in endpoint tumor cell line assays: critical assessment of the application of a single parametric value as a standard criterion to quantify the dose-response effects and new unexplored proposal formats.

The development of convenient tools for describing and quantifying the effects of standard and novel therapeutic agents is essential for the research community, to perform more precise evaluations. Although mathematical models and quantification criteria have been exchanged in the last decade between different fields of study, there are relevant methodologies that lack proper mathematical descriptions and standard criteria to quantify their responses. Therefore, part of the relevant information that can be drawn from the experimental results obtained and the quantification of its statistical reliability are lost. Despite its relevance, there is not a standard form for the in vitro endpoint tumor cell lines' assays (TCLA) that enables the evaluation of the cytotoxic dose-response effects of anti-tumor drugs. The analysis of all the specific problems associated with the diverse nature of the available TCLA used is unfeasible. However, since most TCLA share the main objectives and similar operative requirements, we have chosen the sulforhodamine B (SRB) colorimetric assay for cytotoxicity screening of tumor cell lines as an experimental case study. In this work, the common biological and practical non-linear dose-response mathematical models are tested against experimental data and, following several statistical analyses, the model based on the Weibull distribution was confirmed as the convenient approximation to test the cytotoxic effectiveness of anti-tumor compounds. Then, the advantages and disadvantages of all the different parametric criteria derived from the model, which enable the quantification of the dose-response drug-effects, are extensively discussed. Therefore, model and standard criteria for easily performing the comparisons between different compounds are established. The advantages include a simple application, provision of parametric estimations that characterize the response as standard criteria, economization of experimental effort and enabling rigorous comparisons among the effects of different compounds and experimental approaches. In all experimental data fitted, the calculated parameters were always statistically significant, the equations proved to be consistent and the correlation coefficient of determination was, in most of the cases, higher than 0.98.

Photodynamic therapy for the treatment of complex anal fistula.

BACKGROUND: Photodynamic therapy (PDT) is a new procedure for the treatment of anal fistula. This preliminary study was designed to investigate the safety and effectiveness of this new technique in the treatment of anal fistula. METHODS: Ten patients were treated with PDT. Intralesional 5-aminolevulinic acid (ALA) 2% was directly injected into the fistula. The internal and external orifices were closed. After an incubation period of 2 h, the fistula was irradiated using an optical fibre connected to a red laser (MULTIDIODE 630 PDT, INTERmedic, Spain) operating at 1 W/cm for 3 min (180 Joules). Patient demographics, operation notes and complications were recorded. RESULTS: There were no complications. The average length of patient follow-up was 14.9 months (range 12-20 months). We could observe primary healing in eight patients (80%). Two patients (20%) showed persistence of suppuration after the operation. No patient reported incontinence postoperatively. CONCLUSIONS: PDT is a potential sphincter-saving procedure that is safe, simple and minimally invasive and has a high success rate.

Characterization of Surgical Procedures in the Spanish Mohs Surgery Registry (REGESMOHS) for 2013-2015. / Descripción de las intervenciones quirúrgicas recogidas en el registro español de cirugía de Mohs (REGESMOHS) (2013-2015).

INTRODUCTION: The Spanish Mohs Surgery Registry is used to collect data on the use and outcomes of Mohs micrographic surgery (MMS) in Spain. The aim of this study was to describe perioperative and intraoperative data recorded for MMS procedures performed between July 2013 (when the registry started) and January 2016. MATERIAL AND METHODS: Prospective cohort study of data from 18 hospitals. The data collected included type of anesthesia, surgical technique, hospital admission, number of Mohs stages, management of preoperative risk factors, additional treatments, previous treatments, type of tumor, operating time, and complications. RESULTS: Data were available for 1796 operations. The most common tumor treated by MMS was basal cell carcinoma (85.96%), followed by squamous cell carcinoma (6.18%), lentigo maligna (2.81%), and dermatofibrosarcoma protuberans (1.97%). Primary tumors accounted for 66.9% of all tumors operated on; 19.2% of tumors were recurrent and 13.9% were persistent. The most common previous treatment was surgical. MMS was mostly performed under local anesthesia (86.7% of cases) and as an outpatient procedure (71.8%). The frozen section technique was used in 89.5% of cases. One stage was needed to achieve tumor-free margins in 56.45% of patients; 2 stages were required in 32.1% of patients, 3 in 7.1%%, 4 in 2.7%, and 5 or more in 1.8%. The defect was reconstructed by the dermatologist in 98% of patients and the most common technique was flap closure (47.2%). Intraoperative complications were recorded for just 1.62% of patients and the median (interquartile range) duration of surgery was 75 (60-100) minutes. CONCLUSION: The characteristics of the patients and tumors treated by MMS are similar to those reported for similar studies in other geographic areas. Lentigo maligna and dermatofibrosarcoma protuberans accounted for a higher proportion of cases in our series, and repair of the surgical defect by a dermatologist was also more common. Operating times in MMS are not much longer than those reported for other procedures and the rate of intraoperative complications is very low.

Carbon roadmap from syngas to polyhydroxyalkanoates in Rhodospirillum rubrum.

The gasification of organic waste materials to synthesis gas (syngas), followed by microbial fermentation, provides a significant resource for generating bioproducts such as polyhydroxyalkanoates (PHA). The anaerobic photosynthetic bacterium, Rhodospirillum rubrum, is an organism particularly attractive for the bioconversion of syngas into PHAs. In this study, a quantitative physiological analysis of R. rubrum was carried out by implementing GC-MS and HPLC techniques to unravel the metabolic pathway operating during syngas fermentation that leads to PHA production. Further, detailed investigations of the central carbon metabolites using (13) C-labelled substrate showed significant CO2 assimilation (of 40%) into cell material and PHA from syngas carbon fraction. By a combination of quantitative gene expression and enzyme activity analyses, the main role of carboxylases from the central carbon metabolism in CO2 assimilation was shown, where the Calvin-Benson-Bassham cycle (CBB) played a minor role. This knowledge sheds light about the biochemical pathways that contribute to synthesis of PHA during syngas fermentation being valuable information to further optimize the fermentation process.

Skin Flaps for the Repair of Multiple Adjacent Tumors.

In daily clinical practice, the dermatologic surgeon frequently has to excise closely adjacent tumors in the facial region. In such cases, planning of an appropriate reconstruction technique is essential. The aim is to treat all of the lesions in a single surgical intervention, if possible, and to achieve a good functional and cosmetic outcome. We present 5 patients in whom a single flap was used to repair multiple adjacent defects.

A new and general model to describe, characterize, quantify and classify the interactive effects of temperature and pH on the activity of enzymes.

We suggest a new and general model to describe the effects of temperature (T) and pH on the catalytic activity of enzymes. Despite the abundance of models to describe those effects, the current proposals are unsatisfactory, except for specific experimental cases in which the interactive mechanism between the two variables does not exist. For both variables, our solution analyses the activated and deactivated phases of an enzyme as phenomena of different nature. The system is described with independent probability functions. The interactive effects between T and pH are introduced with simple auxiliary functions. These functions describe the variations induced by each variable in the parameters that define the effects of the other. The structure of the resulting equation is, in theory and practice, very regular, which facilitates its use, and it is highly descriptive in different scenarios with or without interactive effects. The model was tested on three different enzymatic systems which are specifically designed to produce data for the evaluation of the effect of T and pH on the enzyme activity (A). Afterwards, our model was validated using results from other authors. Briefly, the authors found that: (1) other available models that were compared with our proposal were inefficient and in all cases our model provided the only statistically consistent solution; (2) in four cases, the enzymatic activity could only be explained if interactive effects are accepted; (3) synergy and antagonism concepts for the interaction between T and pH were described and classified; and (4) our solution is universal and independent of the structure of an enzyme and the reaction concerned.

Reconstruction of Surgical Defects of the Labial Commissure.

The main objective of oncologic dermatologic surgery is the complete excision of skin tumors. During reconstruction of the defect, we must attempt to preserve function and cosmetic appearance. At the labial commissure, fibers from the superior and inferior portions of the orbicularis oris muscle intersect and the vermillion inserts onto the modiolus, a complex, cone-shaped structure at the angle of the mouth. Surgical reconstruction of the labial commissure is challenging because of the need to preserve sphincter function and cosmetic symmetry. We present a number of cases of surgical defects at the labial commissure and describe the reconstruction techniques used. We also propose an algorithm to help determine the most suitable technique for different cases.

Description of Patients Undergoing Mohs Surgery in Spain: Initial Report on Data From the Spanish Registry of Mohs Surgery (REGESMOHS).

INTRODUCTION: The Spanish registry of Mohs micrographic surgery started collecting data in July 2013. The aim of the registry is to report on the use of this technique in Spain and the outcomes achieved. In the present article, we describe the characteristics of patients and the tumors treated. MATERIAL AND METHODS: This is a prospective cohort study of patients treated with Mohs micrographic surgery. The participating centers are hospitals where at least one intervention of this type is performed each week. All patients considered for Mohs micrographic surgery in participating centers are included in the registry except those who have been declared legally incompetent. RESULTS: Between July 2013 and October 2014, data from 655 patients were included in the registry. The most common tumor involved was basal cell carcinoma, and the most common histological subtype was infiltrative basal cell carcinoma. Most of the tumors treated were located on the face or scalp, and the most common site was the nose. Almost 40% of the tumors treated were recurrent or persistent, and preoperative tumor size was similar to that reported in other European studies and in Australia. In total, 45.5% of patients had received previous surgical treatment. CONCLUSION: The findings are similar to those reported in other studies, and the data collected are useful for assessing whether the results of studies carried out elsewhere are applicable in Spain.

Oversimplification and overstandardization in biological methods: sperm bioassays in ecotoxicology as a case of study and a proposal for their reformulation.

An interesting toxicological bioassay (fertilization inhibition in sea urchin) uses as assessment criterion a variable (fertilization ratio) whose variation with time creates two types of difficulties. First, it fails to distinguish between the toxic effect and the spontaneous decline in the sperm activity, causing some inconsistencies. Second, the sensitivity of the fertilization ratio to many other variables of the system requires a complex standardization, constraining the achievement of the method without solving its main problem. Our proposal consists of using a parameter (sperm half-life) as the response of the assay, and describing explicitly the behavior of the system as a simultaneous function of dose and time. This new focus is able to solve the problematic character of the results based on the fertilization ratio and by using the same data set which is required by the conventional approach; it simplifies the protocol, economizes experimental effort, provides unambiguous and robust results, and contributes to the detection of an artefactual temperature effect, which is not very evident under the usual perspective. Potential application of this new approach to the improvement of other formally similar bioassays is finally suggested.