International Delphi Expert Consensus on Safe Return to Surgical and Endoscopic Practice: From the Coronavirus Global Surgical Collaborative.

OBJECTIVE: The aim of this work is to formulate recommendations based on global expert consensus to guide the surgical community on the safe resumption of surgical and endoscopic activities. BACKGROUND: The COVID-19 pandemic has caused marked disruptions in the delivery of surgical care worldwide. A thoughtful, structured approach to resuming surgical services is necessary as the impact of COVID-19 becomes better controlled. The Coronavirus Global Surgical Collaborative sought to formulate, through rigorous scientific methodology, consensus-based recommendations in collaboration with a multidisciplinary group of international experts and policymakers. METHODS: Recommendations were developed following a Delphi process. Domain topics were formulated and subsequently subdivided into questions pertinent to different aspects of surgical care in the COVID-19 crisis. Forty-four experts from 15 countries across 4 continents drafted statements based on the specific questions. Anonymous Delphi voting on the statements was performed in 2 rounds, as well as in a telepresence meeting. RESULTS: One hundred statements were formulated across 10 domains. The statements addressed terminology, impact on procedural services, patient/staff safety, managing a backlog of surgeries, methods to restart and sustain surgical services, education, and research. Eighty-three of the statements were approved during the first round of Delphi voting, and 11 during the second round. A final telepresence meeting and discussion yielded acceptance of 5 other statements. CONCLUSIONS: The Delphi process resulted in 99 recommendations. These consensus statements provide expert guidance, based on scientific methodology, for the safe resumption of surgical activities during the COVID-19 pandemic.

Efficacy and Safety of Inhaled Glycopyrronium Bromide in COPD: A Randomized, Parallel Group, Dose-Ranging Study (GLIMMER).

This Phase II, randomized, parallel group study was conducted as part of US regulatory requirements to identify the most appropriate dose of the long-acting muscarinic antagonist glycopyrronium bromide (GB) for use in a single-inhaler triple-therapy combination with the inhaled corticosteroid beclomethasone dipropionate plus the long-acting ß2-agonist formoterol fumarate. Eligible subjects were adults with COPD and post-bronchodilator forced expiratory volume in 1 s (FEV1) 40-80% predicted. Subjects were randomized to receive inhaled double-blind GB 6.25, 12.5, 25 or 50 µg or placebo, all twice daily (BID), or open-label tiotropium 18 µg once daily for six weeks. The primary objective was to evaluate the efficacy of GB versus placebo in terms of FEV1 area under the curve between 0 and 12 h at Week 6. Of 733 subjects randomized, 682 (93.0%) completed the study. For the primary endpoint, all GB doses were superior to placebo (p < 0.05), with a dose-response up to 25 µg BID, and 25 and 50 µg BID both superior to 6.25 µg BID (p < 0.05). Results for the secondary spirometry endpoints were consistent with the primary endpoint. Overall, the efficacy of GB 25 and 50 µg BID was broadly consistent with that of tiotropium. The incidence of adverse events, both overall and for the most common preferred terms, was low and similar in all treatment groups, including placebo (overall, 22.3-29.3%). Based on the totality of the efficacy and safety data, the optimal GB dose is 25 µg BID.

[Pancreatoblastoma in a pediatric patient: a case report]. / Pancreatoblastoma en paciente pediátrico: reporte de caso.

Pancreoblastoma is a very rare tumor that originates from the exocrine epithelial cells of the pancreas. However, it is the most frequent pancreatic tumor in children. It usually appears in the first decade of life with an average of 5 years old. The clinical manifestations are usually unspecific, being the abdominal pain and the abdominal mass the most frequent. The radiological signs are not very well described in medical literature. The definite diagnosis should always be established with biopsia and histological examination. Here it is presented a clinical case of pancreoblastoma with unusual involvement of a major duodenal papilla in a pediatric patient.

Altered expression of CKs 14/20 is an early event in a rat model of multistep bladder carcinogenesis.

Cytokeratins (CKs) 14 and 20 are promising markers for diagnosing urothelial lesions and for studying their prognosis and histogenesis. This work aimed to study the immunohistochemical staining patterns of CK14/20 during multistep carcinogenesis leading to papillary bladder cancer in a rat model. Thirty female Fischer 344 rats were divided into three groups: group 1 (control); group 2, which received N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 20 weeks plus 1 week without treatment; and group 3, which received BBN for 20 weeks plus 8 weeks without treatment. Bladder lesions were classified histologically. CK14 and CK20 immunostaining was assessed according to its distribution and intensity. In control animals, 0-25% of basal cells and umbrella cells stained positive for CK14 and CK20 respectively. On groups 2 and 3, nodular hyperplastic lesions showed normal CK20 and moderately increased CK14 staining (26-50% of cells). Dysplasia, squamous metaplasia, papilloma, papillary tumours of low malignant potential and low- and high-grade papillary carcinomas showed increased CK14 and CK20 immunostaining in all epithelial layers. Altered CK14 and CK20 expression is an early event in urothelial carcinogenesis and is present in a wide spectrum of urothelial superficial neoplastic and preneoplastic lesions.

Maximum power point tracking dataset for a wind energy conversion system based on a reverse-controller for a multilevel boost converter.

The database here contains experimental data relevant to an original maximum power point tracking controller for an experimental direct-drive full-variable-speed full-rated converter Type IV Wind Energy Conversion System in standalone operation. The main goal is to maximize power extraction by controlling the duty cycle of a multilevel boost converter, which is responsible for adjusting the angular speed of a permanent magnet synchronous generator coupled to a three-phase induction motor that emulates the wind turbine. Two data acquisition cards with the appropriate signal conditioners were used to obtain measurements of the generator angular speed, output current, and output voltage at the terminals of the multilevel converter. In addition, data related to power coefficient, tip speed ratio, duty cycle, and output power are also included. Two PCs in a Linux real-time platform were used for the emulation, control, and data collection processes. On the other hand, Matlab was used to analyze the data to evaluate the controller's performance to maximize wind power extraction. The database is freely accessible at http://dx.doi.org/10.17632/363d24mcb6.2. This dataset [1] represents a resource for wind power specialists who develop algorithms for wind energy optimization.

Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial.

In the coronavirus efficacy (COVE) phase 3 clinical trial, vaccine recipients were assessed for neutralizing and binding antibodies as correlates of risk for COVID-19 disease and as correlates of protection. These immune markers were measured at the time of second vaccination and 4 weeks later, with values reported in standardized World Health Organization international units. All markers were inversely associated with COVID-19 risk and directly associated with vaccine efficacy. Vaccine recipients with postvaccination 50% neutralization titers 10, 100, and 1000 had estimated vaccine efficacies of 78% (95% confidence interval, 54 to 89%), 91% (87 to 94%), and 96% (94 to 98%), respectively. These results help define immune marker correlates of protection and may guide approval decisions for messenger RNA (mRNA) COVID-19 vaccines and other COVID-19 vaccines.

Clinical impact of obesity on respiratory diseases: A real-life study.

BACKGROUND: Obesity has become an epidemic that affects Mexico; significantly interferes with respiratory physiology by decreasing lung volumes, therefore, might be considered as a relevant risk factor associated with the development of respiratory diseases. OBJECTIVE: Our primary outcome was to analyze the frequency and risk factors between obesity and respiratory disease in the Mexican population. MATERIALS AND METHODS: An observational, single-center, descriptive study, which included the totality of patients who were referred for medical attention at the Respiratory and Thorax Surgery Unit at the Hospital Regional de Alta Especialidad de la Península de Yucatán during the period from January 2015 to December 2018. The cases were grouped based on the existence or not of respiratory disease and the presence or absence of obesity (body mass index [BMI] >30 kg/m2). RESULTS: A total of 1167 patients were included; about 39% of the population had average BMI 36.5 kg/m2. The primary respiratory diseases in obese patients were Obstructive Sleep Apnea Syndrome (OSAS, 19%) and asthma (15%). The logistic regression analysis showed a direct association between the presence of obesity with respiratory disease (odds ratio 1.58, 95% confidence interval 1.22-2.03, P < 0.001), the strength of this association was related with asthma and OSAS. CONCLUSION: The presence of obesity is an independent risk factor for respiratory disease, primarily for OSAS and asthma.

Method for maximum power point tracking and verification by modeling a unified wind energy conversion system.

Maximum power point tracking in wind turbines is a topic that has attracted many researchers' interest; however, the studies presented are usually carried out only at the simulation level, so they lack a verification in the system through real measurements. On the other hand, the system's modeling is usually quite complex, making it challenging to meet the control objectives. There are unified models in which the system is treated in a generalized way according to various research purposes. This work presents a methodology that simplifies the unified system through a series of dynamic tests that applied to obtained a simplified model much easier to handle without sacrificing the system's dynamic richness. • An alternative approach for a unified wind energy conversion system is established by employing physical dynamic tests applied to the wind set. • A maximum power point tracking is verified by real-time measurements managed by an open-source platform. • Methodology related to electronic instrumentation and programming is described so the tests can be reproduced without much difficulty.

Intermittent BRAF inhibition in advanced BRAF mutated melanoma results of a phase II randomized trial.

Combination treatment with BRAF (BRAFi) plus MEK inhibitors (MEKi) has demonstrated survival benefit in patients with advanced melanoma harboring activating BRAF mutations. Previous preclinical studies suggested that an intermittent dosing of these drugs could delay the emergence of resistance. Contrary to expectations, the first published phase 2 randomized study comparing continuous versus intermittent schedule of dabrafenib (BRAFi) plus trametinib (MEKi) demonstrated a detrimental effect of the "on-off" schedule. Here we report confirmatory data from the Phase II randomized open-label clinical trial comparing the antitumoral activity of the standard schedule versus an intermittent combination of vemurafenib (BRAFi) plus cobimetinib (MEKi) in advanced BRAF mutant melanoma patients (NCT02583516). The trial did not meet its primary endpoint of progression free survival (PFS) improvement. Our results show that the antitumor activity of the experimental intermittent schedule of vemurafenib plus cobimetinib is not superior to the standard continuous schedule. Detection of BRAF mutation in cell free tumor DNA has prognostic value for survival and its dynamics has an excellent correlation with clinical response, but not with progression. NGS analysis demonstrated de novo mutations in resistant cases.

Immune Correlates Analysis of the mRNA-1273 COVID-19 Vaccine Efficacy Trial.

BACKGROUND: In the Coronavirus Efficacy (COVE) trial, estimated mRNA-1273 vaccine efficacy against coronavirus disease-19 (COVID-19) was 94%. SARS-CoV-2 antibody measurements were assessed as correlates of COVID-19 risk and as correlates of protection. METHODS: Through case-cohort sampling, participants were selected for measurement of four serum antibody markers at Day 1 (first dose), Day 29 (second dose), and Day 57: IgG binding antibodies (bAbs) to Spike, bAbs to Spike receptor-binding domain (RBD), and 50% and 80% inhibitory dilution pseudovirus neutralizing antibody titers calibrated to the WHO International Standard (cID50 and cID80). Participants with no evidence of previous SARS-CoV-2 infection were included. Cox regression assessed in vaccine recipients the association of each Day 29 or 57 serologic marker with COVID-19 through 126 or 100 days of follow-up, respectively, adjusting for risk factors. RESULTS: Day 57 Spike IgG, RBD IgG, cID50, and cID80 neutralization levels were each inversely correlated with risk of COVID-19: hazard ratios 0.66 (95% CI 0.50, 0.88; p=0.005); 0.57 (0.40, 0.82; p=0.002); 0.42 (0.27, 0.65; p<0.001); 0.35 (0.20, 0.61; p<0.001) per 10-fold increase in marker level, respectively, multiplicity adjusted P-values 0.003-0.010. Results were similar for Day 29 markers (multiplicity adjusted P-values <0.001-0.003). For vaccine recipients with Day 57 reciprocal cID50 neutralization titers that were undetectable (<2.42), 100, or 1000, respectively, cumulative incidence of COVID-19 through 100 days post Day 57 was 0.030 (0.010, 0.093), 0.0056 (0.0039, 0.0080), and 0.0023 (0.0013, 0.0036). For vaccine recipients at these titer levels, respectively, vaccine efficacy was 50.8% (-51.2, 83.0%), 90.7% (86.7, 93.6%), and 96.1% (94.0, 97.8%). Causal mediation analysis estimated that the proportion of vaccine efficacy mediated through Day 29 cID50 titer was 68.5% (58.5, 78.4%). CONCLUSIONS: Binding and neutralizing antibodies correlated with COVID-19 risk and vaccine efficacy and likely have utility in predicting mRNA-1273 vaccine efficacy against COVID-19. TRIAL REGISTRATION NUMBER: COVE ClinicalTrials.gov number, NCT04470427.

High Rate of Non-Human Feeding by Aedes aegypti Reduces Zika Virus Transmission in South Texas.

Mosquito-borne viruses are emerging or re-emerging globally, afflicting millions of people around the world. Aedes aegypti, the yellow fever mosquito, is the principal vector of dengue, Zika, and chikungunya viruses, and has well-established populations across tropical and subtropical urban areas of the Americas, including the southern United States. While intense arboviral epidemics have occurred in Mexico and further south in the Americas, local transmission in the United States has been minimal. Here, we study Ae. aegypti and Culex quinquefasciatus host feeding patterns and vertebrate host communities in residential environments of South Texas to identify host-utilization relative to availability. Only 31% of Ae. aegypti blood meals were derived from humans, while 50% were from dogs and 19% from other wild and domestic animals. In Cx. quinquefasciatus, 67% of blood meals were derived from chicken, 22% came from dogs, 9% from various wild avian species, and 2% from other mammals including one human, one cat, and one pig. We developed a model for the reproductive number, R0, for Zika virus (ZIKV) in South Texas relative to northern Mexico using human disease data from Tamaulipas, Mexico. We show that ZIKV R0 in South Texas communities could be greater than one if the risk of human exposure to Ae. aegypti bites in these communities is at least 60% that of Northern Mexico communities. The high utilization of non-human vertebrates and low risk of human exposure in South Texas diminishes the outbreak potential for human-amplified urban arboviruses transmitted by Ae. aegypti.

Correction of nasojugal groove with tunnelled fat graft.

BACKGROUND: Pronounced nasojugal sulcus (tear trough deformity) is a frequent and distressing symptom in aesthetic palpebral surgery. The sliding fat technique using the transcutaneous or transconjunctival approach has proven to be considerably useful in patients with clinically evident fat bags. In the absence of fat bags, commonly used techniques can lead to unpredictable (and frequently less than optimal) results. OBJECTIVE: The authors report their experience with correcting the nasojugal groove in the absence of palpebral fat bags by use of a one-piece, free fat graft as an alternative to autologous fat injections or the placement of alloplastic materials. METHODS: The authors conducted a retrospective study of a consecutive series of 34 patients (33 women and one man) between 42 and 57 years of age. In all cases, small, free fat grafts harvested from the medial fat compartment of the upper eyelid were placed precisely under the depression through two stab incisions in the suborbicularis plane, filling in the groove. RESULTS: Results were considered excellent in 24 out of the 34 patients. Results in the remaining 10 patients were rated as good, in most cases because of mild undercorrection. All patients expressed a high degree of satisfaction. Recovery time was very short and no eye or eyelid complications were observed. CONCLUSIONS: Correction of the nasojugal groove with a tunnelled fat graft causes minimal tissue trauma and allows exact placement of the graft. The upper palpebral fat has unique characteristics that render it an ideal graft material for correction of the nasojugal groove in patients with no concomitant lower fat bags. This procedure offers more predictable results and a lower incidence of adverse effects than more commonly used techniques.

Peripheral Vascular Trauma in Pediatrics: A Case Report and Literature Review.

Vascular lesions constitute an important cause of morbidity and mortality, including functional disability. Their poor documentation in the literature suggests a low frequency in the pediatric age range. Herein, we describe the case of an 11-year-old-boy with an isolated radial artery injury. The patient initially presented with active bleeding from a lacerated wound. He was intervened on multiple occasions for hematoma formation and suture dehiscence at a primary care center from his community. During his admission, he required a blood transfusion for active bleeding. Vascular exploration was performed, and radial artery lesion was managed by ligation.

Physiological responses in horses, donkeys and mules sold at livestock markets.

The horse welfare at markets includes fatigue, fear, fasting, dehydration and injuries. However, the scientific literature contains no readily-available information on the physiology responses of equids sold in livestock markets. The objective of the present study was to evaluate the effect of holding in livestock markets on gas exchange, the acid-base balance, energy metabolism, and the mineral and water balance in 4 types of horses (Equus caballus), donkeys (Equus asinus) and mules ((Equus asinus × Equus caballus). To this end, a total of 1,438 equine were utilized, after classification into six groups, as follows: mules, donkeys, culled horses, charrería horses (Mexican rodeo horses), foals, and ponies. The time intervals evaluated were 1 and 5 h. During the study, the animals received only water ad libitum. The physiological blood indicators assessed were: PvCO2 (mm Hg) and PvO2 (mm Hg) pressure, pH, glucose (mg/dL), lactate (mg/dL), bicarbonate levels (mmol/L), hematocrit (%), Na+, K+ and Ca2+ (mmol/L). The animals that presented the most marked physiological alterations were the mules and donkeys. The mules that remained in the corrals for 1 h presented increases (P < 0.0001) in the values for pO2, glucose, hematocrit and blood pH, compared to reference values (RV), while the donkeys had increases (P < 0.0001) in glucose and hematocrit values. By the end of the first hour at the exhibition corrals the equine were dehydrated, suffered fatigue, and suffered metabolic and compensatory problems, probably due to the combined effects of a series of factors that include transport and inadequate handling.

Impact of treatment in long-term survival patients with follicular lymphoma: A Spanish Lymphoma Oncology Group registry.

BACKGROUND: Follicular lymphoma is the second most common non-Hodgkin lymphoma in the United States and Europe. However, most of the prospective randomized studies have very little follow-up compared to the long natural history of the disease. The primary aim of this study was to investigate the long-term survival of our series of patients with follicular lymphoma. PATIENTS AND METHODS: A total of 1074 patients with newly diagnosed FL were enrolled. Patients diagnosed were prospectively enrolled from 1980 to 2013. RESULTS: Median follow-up was 54.9 months and median overall survival is over 20 years in our series. We analyzed the patients who are still alive beyond 10 years from diagnosis in order to fully assess the prognostic factors that condition this group. Out of 166 patients who are still alive after more than 10 years of follow-up, 118 of them (73%) are free of evident clinical disease. Variables significantly associated with survival at 10 years were stage < II (p <0.03), age < 60 years (p <0.0001), low FLIPI (p <0.002), normal ß2 microglobulin (p <0.005), no B symptoms upon diagnosis (p <0.02), Performance Status 0-1 (p <0.03) and treatment with anthracyclines and rituximab (p <0.001), or rituximab (p <0.0001). CONCLUSIONS: A longer follow-up and a large series demonstrated a substantial population of patients with follicular lymphoma free of disease for more than 10 years.

DNA content analysis, expression of Ki-67 and p53 in rat urothelial lesions induced by N-butyl-N-(4-hydroxybutyl) nitrosamine and treated with mitomycin C and bacillus Calmette-Guérin.

N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced urothelial carcinogenesis is a useful model for studying urothelial carcinogenesis. Here, the DNA content and the expression of Ki-67 and p53 in urothelial lesions induced by BBN and treated with mitomycin C (MMC) and Bacillus Calmette-Guérin (BCG) were investigated. Female Fisher 344 rats were distributed into five groups treated with 0.05% BBN in their drinking water for 20 weeks. Ten animals were used as negative control. Intravesical instillations were performed with MMC, BCG and physiological saline solution (PSS), once per week, for 6 weeks. The animals were sacrificed 1 week after the last intravesical instillation. DNA ploidy analysis was carried out by static cytometry. Ki-67 and p53 were analysed immunohistochemically in paraffin-embedded tissue. The incidence of lesions developed in rats with PSS was greater than in rats instilled with MMC and BCG. The incidence of aneuploidy was lower in tumours treated with MMC and BCG. Low- and high-grade papillary carcinoma treated with MMC and BCG showed a decrease in labelling index and an increase of apoptotic index. The proliferative index was correlated with the apoptotic index (r=0.438, p<0.01). Significant correlations were also found between the proliferative index and lesion, and the apoptotic index and lesion (r=0.425, p<0.01 and r=0.275, p<0.01), respectively. A significant correlation was found between ploidy and the apoptotic index (r=0.245, p<0.05). Our results provide information on the biological behaviour of chemically-induced bladder tumours treated with MMC and BCG.

Effectiveness of chemotherapy in advanced differentiated thyroid cancer: a systematic review.

In differentiated thyroid carcinoma refractory to radioactive iodine (CDT-RTI), chemotherapy has been considered for decades to be the only systemic therapy with palliative purpose. Phase II studies assessing the efficacy of different chemotherapy outlines have been published. Nevertheless, phase III studies in these tumours have not been performed. Our objective is to evaluate the effectiveness of chemotherapy in patients with CDT-RTI by a systematic review of published studies. Systematic research of the literature in Medline and Embase databases (among others) was carried out. The full texts of selected references were analysed by two independent reviewers and then assessed for risk of bias in each study. We also extracted data using specifically designed questionnaires. Later, a qualitative synthesis of results was performed and pooled data were calculated. We found that 16 studies with 473 patients published in the last 40 years were included out of 509 identified references in databases. Thirteen studies (176 patients) included data on response to treatment and histology. Four studies included 70 patients only with well-differentiated non-medullary tumours. Response rate (RR) was 22.1% (0-57%) for 13 studies, 25% for the 176 patients and 27.1% for the 70 patients, with 2.5, 3.4 and 2.8% complete responses respectively. Survival times could not be assessed or pooled due to the lack of data and heterogeneity of the studies, and was determined to have a high risk of bias. Although it has not been possible to find solid evidence about the efficacy of chemotherapy, the results shown indicate that it may have some effectiveness, although this should be proven with well-designed studies using modern drugs.

Sam68 Mediates the Activation of Insulin and Leptin Signalling in Breast Cancer Cells.

Obesity is a well-known risk factor for breast cancer development in postmenopausal women. High insulin and leptin levels seem to have a role modulating the growth of these tumours. Sam68 is an RNA-binding protein with signalling functions that has been found to be overexpressed in breast cancer. Moreover, Sam68 may be recruited to insulin and leptin signalling pathways, mediating its effects on survival, growth and proliferation in different cellular types. We aimed to study the expression of Sam68 and its phosphorylation level upon insulin and leptin stimulation, and the role of Sam68 in the proliferative effect and signalling pathways that are activated by insulin or leptin in human breast adenocarcinoma cells. In the human breast adenocarcinoma cell lines MCF7, MDA-MB-231 and BT-474, Sam68 protein quantity and gene expression were increased upon leptin or insulin stimulation, as it was checked by qPCR and immunoblot. Moreover, both insulin and leptin stimulation promoted an increase in Sam68 tyrosine phosphorylation and negatively regulated its RNA binding capacity. siRNA was used to downregulate Sam68 expression, which resulted in lower proliferative effects of both insulin and leptin, as well as a lower activation of MAPK and PI3K pathways promoted by both hormones. These effects may be partly explained by the decrease in IRS-1 expression by down-regulation of Sam68. These results suggest the participation of Sam68 in both leptin and insulin receptor signaling in human breast cancer cells, mediating the trophic effects of these hormones in proliferation and cellular growth.

Mastopexy utilizing a dermoglandular hammock flap.

BACKGROUND: Many procedures have been described in the search for the ideal mastopexy technique, ranging from simple cutaneous reduction, with or without glandular remodelling, to the use of dermal flaps fixed to the pectoral fascia, or even the use of silicone mesh or sheets. OBJECTIVE: We describe a technique that uses a dermoglandular hammock flap to achieve optimal position and shape of the breast; well located, good quality scars that are as short as possible; and satisfactory early- and long-term results. METHODS: A superior pedicle dermoglandular flap was raised from the lower pole of the breast and transposed to the upper pole. The flap is fixed like a hammock to the pectoral fascia and the wedge-shaped donor defect is closed by approximation and fixation of the medial and lateral pillars with absorbable sutures, thus releasing the tension in the skin suture line. RESULTS: Twenty-eight patients aged 19 to 58 years underwent the procedure. Adequate shape and projection were achieved in all cases. Partial dehiscence of the suture line developed in 1 patient. The scar quality was excellent, except in 2 cases in which some degree of temporary hypertrophy occurred. CONCLUSIONS: In our experience with this technique, we obtained satisfactory position and shape; good quality, well-placed scars; long-lasting results; and preservation of the patient's ability to breast feed. The technique is simple to perform and is indicated in cases of moderate ptosis.

Vascular wall: potential target for the physicochemical effects of cis-unsaturated free fatty acids.

Diets rich in monounsaturated cis-FFA (cis FFA) are associated with a significant reduction of cardiovascular risk. Although several different mechanisms have been proposed to explain this protective effect, the biochemical processes involved have not been fully elucidated. It has been shown that upon their incorporation into the plasma membrane, cis FFA induce a marked perturbation of the lipid domains, altering membrane fluidity as well as lipid-lipid and lipid-protein interactions in the bilayer plane. During the last few years, several lines of evidence have shown that these perturbations disrupt the activity of several membrane proteins and enzymatic systems. As a result, several critical transmembrane signaling systems, including the Ins(1,4,5)P(3)/DAG/[Ca(2+)](i), the cAMP/PKA, and the voltage-operated Ca(2+) influx are strongly inhibited by cis FFA in different experimental models. Furthermore, this inhibition is associated with alterations in the timing of the cell cycle as well as in the final steps of the secretory pathway. We propose that this complex set of biological actions exerted by cis FFA at the plasma membrane may contribute to explain the protective roles that these molecules appear to exert on the vascular wall.