Antioxidants in Photoaging: From Molecular Insights to Clinical Applications.

Photoaging (PA) is considered a silent disease affecting millions of people globally and is defined as skin damage due to prolonged exposure to ultraviolet radiation (UVR) from the sun. Physiologically, the skin is in a state of renewal and synthesis of components of the extracellular matrix (ECM). However, exposure to UVR affects the production of the ECM, and the functioning and response of skin cells to UVR begins to change, thus expressing clinical and phenotypic characteristics of PA. The primary mechanisms involved in PA are direct damage to the DNA of skin cells, increases in oxidative stress, the activation of cell signaling pathways responsible for the loss of skin integrity, and cytotoxicity. The medical and scientific community has been researching new therapeutic tools that counteract PA, considering that the damage caused by UVR exceeds the antioxidant defense mechanisms of the skin. Thus, in recent years, certain nutraceuticals and phytochemicals have been found to exhibit potential antioxidant and photoprotective effects. Therefore, the main objective of this review is to elucidate the molecular bases of PA and the latest pharmaceutical industry findings on antioxidant treatment against the progression of PA.

Assessment of Preoperative Anxiety in Cardiac Surgery Patients Lacking a History of Anxiety: Contributing Factors and Postoperative Morbidity.

OBJECTIVES: The aim of this study was to measure the level of preoperative anxiety in patients scheduled for cardiac surgery, identify any influencing clinical factors, and assess the relationship between anxiety and postoperative morbidity. DESIGN: A prospective and consecutive study. SETTING: A single university hospital. PARTICIPANTS: The study comprised 200 patients scheduled for cardiac surgery. INTERVENTIONS: Each patient was asked to grade his or her preoperative anxiety level using the Visual Analogue Scale for Anxiety, Amsterdam Preoperative Anxiety and Information Scale, and set of specific anxiety-related questions. Demographic data (age, sex, body mass index) and anesthetic and surgical data (American Society of Anesthesiologists physical status, EuroSCORE surgical risk, preoperative length of stay, and previous anesthetic experience) were registered. Also, postoperative morbidity was assessed. MEASUREMENTS AND MAIN RESULTS: Twenty-eight percent of the patients developed high preoperative anxiety. The mean Amsterdam Preoperative Anxiety and Information Scale score was 11.4 ± 4.3, and the mean Visual Analogue Scale for Anxiety score was 48 ± 21. Patients scheduled for coronary artery bypass surgery, who had no previous anesthetic experience, and who were hospitalized before surgery, had higher anxiety scores. Coronary bypass surgery (odds ratio 3.026; 1.509-6.067; p = 0.002) was associated independently with preoperative high-level anxiety. Anxiety most commonly was caused by waiting for surgery, not knowing what is happening, fearing not being able to awaken from anesthesia, and being at the mercy of staff. Anxiety did not modify the postoperative course. CONCLUSIONS: In patients waiting to undergo cardiac surgery, both fear of the unknown and lack of information, especially related to the surgery, are crucial factors in high levels of preoperative anxiety in cardiac surgery. Coronary bypass surgery is a determining factor for preoperative anxiety. The anxiety level did not modify the postoperative course in these patients.

Alterations in hemostasis during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is frequently associated with coagulation impairment and perioperative blood transfusion. Our aim was to investigate the impact of each procedure step on hemostasis, as measured by rotational thromboelastometry™ (ROTEM), fibrinogen level and platelet count as a primary outcome, along with its relationship with transfusion needs. METHODS: A prospective longitudinal study was performed. Hemoglobin level, fibrinogen level, platelet count and ROTEM parameters: clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), α-angle (EXTEM, INTEM, FIBTEM) were measured before the procedure, at the end of cytoreductive surgery and after HIPEC. Appropriate statistical tests were used for comparison. A P<.05 was considered as significant. RESULTS: Forty-one women, with median age 54 (range 34-76) were recruited. Cytoreductive surgery was followed by a reduction of hemoglobin level from 11,4±1,5g/dl to 10,6±1,6g/dl, a reduction of serum fibrinogen level from 269±69mg/dl to 230±48mg/dl (P<.01) and MCF decline from 20±10 to 16±8mm (P<.01), in the FIBTEM test. HIPEC was followed by no hemostatic impairment. The number of packed red blood cells administered during patients stay kept a mild significant relationship with both fibrinogen level (ρ = -0.5, P=.002), and MCF EXTEM values (ρ= -0.43, P=0.006), recorded after HIPEC. CONCLUSIONS: The mild observed hemostatic impairment appeared after cytoreductive surgery instead of HIPEC, involving surgical hemorrhage as the most likely responsible factor. Further studies are required to confirm a correlation between transfusion needs and postoperative hemostatic tests.

The Placental Role in Gestational Diabetes Mellitus: A Molecular Perspective.

During pregnancy, women undergo several metabolic changes to guarantee an adequate supply of glucose to the foetus. These metabolic modifications develop what is known as physiological insulin resistance. When this process is altered, however, gestational diabetes mellitus (GDM) occurs. GDM is a multifactorial disease, and genetic and environmental factors play a crucial role in its aetiopathogenesis. GDM has been linked to both macroscopic and molecular alterations in placental tissues that affect placental physiology. This review summarizes the role of the placenta in the development of GDM from a molecular perspective, including hormonal and pro-inflammatory changes. Inflammation and hormonal imbalance, the characteristics dominating the GDM microenvironment, are responsible for placental changes in size and vascularity, leading to dysregulation in maternal and foetal circulations and to complications in the newborn. In conclusion, since the hormonal mechanisms operating in GDM have not been fully elucidated, more research should be done to improve the quality of life of patients with GDM and their future children.

PLXNA2 and LRRC40 as candidate genes in autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disability with high heritability yet the genetic etiology remains elusive. Therefore, it is necessary to elucidate new genotype-phenotype relationships for ASD to improve both the etiological knowledge and diagnosis. In this work, a copy-number variant and whole-exome sequencing analysis were performed in an ASD patient with a complex neurobehavioral phenotype with epilepsy and attention deficit hyperactivity disorder. We identified rare recessive single nucleotide variants in the two genes, PLXNA2 encoding Plexin A2 that participates in neurodevelopment, and LRRC40, which encodes Leucine-rich repeat containing protein 40, a protein of unknown function. PLXNA2 showed the heterozygous missense variants c.614G>A (p.Arg205Gln) and c.4904G>A (p.Arg1635Gln) while LRRC40 presented the homozygous missense variant c.1461G>T (p.Leu487Phe). In silico analysis predicted that these variants could be pathogenic. We studied PLXNA2 and LRRC40 mRNA and proteins in fibroblasts from the patient and controls. We observed a significant PlxnA2 subcellular delocalization and very low levels of LRRC40 in the patient. Moreover, we found a novel interaction between PlxnA2 and LRRC40 suggesting that participate in a common neural pathway. This interaction was significant decreased in the patient's fibroblasts. In conclusion, our results identified PLXNA2 and LRRC40 genes as candidates in ASD providing novel clues for the pathogenesis. Further attention to these genes is warranted in genetic studies of patients with neurodevelopmental disorders, particularly ASD. LAY SUMMARY: Genomics is improving the knowledge and diagnosis of patients with autism spectrum disorder (ASD) yet the genetic etiology remains elusive. Here, using genomic analysis together with experimental functional studies, we identified in an ASD complex patient the PLXNA2 and LRRC40 recessive genes as ASD candidates. Furthermore, we found that the proteins of these genes interact in a common neural network. Therefore, more attention to these genes is warranted in genetic studies of patients with neurodevelopmental disorders, particularly ASD.

[Late preterm infants in Spain: Experience of the 34-36 Neonatal Group]. / Prematuro tardío en España: experiencia del Grupo SEN34-36.

INTRODUCTION: Late preterm (LP) infants (34 -36 weeks of gestation) are the largest group of preterm infants and also the least studied so far. In order to improve their care and reduce the impact of their increased morbidity and mortality, it is essential to know the current situation in Spain. POPULATION AND METHOD: Clinical-epidemiological variables of the LP population of 34 participating hospitals were prospectively collected from 1 April 2011 to 31 March 2016, and were then compared with the Minimum Perinatal Data Set for term births in the database. RESULTS: Of the 9,121 LP studied, 21.7% of 34, 30.8% of 35, and 47.5% of 36 weeks of gestation. The mortality rate was 2.8%. More than one-quarter (27.7%) were multiple pregnancies. Maternal disease were identified in 47.1% and 41.4% were pathological gestation. Just under half (47.9%) were by Caesarean section and 18.8% were of unknown origin or unjustified. No known cause of prematurity was found in 29%, and 3.1% were recognized as unjustified?caesarean?. Just under half (47%) of the LP were breastfed, and 58.6% required admission to neonatology, with 15.2% to Neonatal Intensive Care Unit. Coded diagnoses were recorded in 46.2%, with the most frequent being jaundice, 43.5%, hypoglycaemia, 30%, and respiratory disorders with 28.7%. CONCLUSIONS: The large sample of LP studied helps us to highlight the higher neonatal mortality and morbidity that this population suffers and the unavoidable relationship of its incidence with multiparity, maternal aging, and the still numerous inductions of labour and unjustified elective caesareans.

Biochemical and clinical characterization of metabolic phenotypes: a cross-sectional study from Maracaibo city, Venezuela.

Background: In 1980, Reuben Andresen observed that in certain individuals, obesity did not increase mortality, introducing an atypical phenotype called "healthy obese". Other studies reported that 10-15 % of lean individuals presented insulin resistance, hyperglycemia and dyslipidemia. The objective of this study was to evaluate biochemical and clinical characteristics of metabolic phenotypes in Maracaibo city. Methods: A descriptive, cross-sectional study with a randomized multistage sampling was performed including 1226 non diabetic individuals from both sexes. For phenotype definition, the subjects were first classified according to their BMI into Normal-Weight, Overweight and Obese; then divided in metabolically healthy and unhealthy using a two-step analysis cluster. To evaluate the relationship with coronary risk, a multiple logistic regression model was performed. Results: In the studied population, 5.2% (n=64) corresponded to unhealthy lean subjects, and 17.4% (n=217) to healthy obese subjects. Metabolically unhealthy normal-weight (MUNW) phenotype was found in males in 53.3% in contrast to 51.3% of metabolically unhealthy obese (MUO) phenotype found in females. An association between metabolically unhealthy phenotypes and a higher risk of a coronary event was found, especially for obese individuals (MHO: OR=1.85 CI95%: 1.11-3.09; p=0.02 and MUO: OR=2.09 CI95%: 1.34-3.28; p<0.01). Conclusion: Individuals with atypical metabolic phenotypes exist in Maracaibo city. Related factors may include insulin resistance, basal glucose levels, and triglycerides levels. Lastly, cardiovascular risk exhibited by healthy obese individuals should be classified in categories of major coronary risk related to lean subjects.

The approach of fused fissures with fissureless technique decreases the incidence of persistent air leak after lobectomy.

OBJECTIVE: To evaluate two different approaches used to perform fused fissures in lobectomies in terms of persistent air leak (PAL) and their impact on length of hospital stay. METHODS: One hundred and nineteen patients underwent lobectomy or bilobectomy in our unit. We focused on patients with fused fissures (63 patients), all of whom were selected intraoperatively based on predefined criteria. These patients with incomplete fissures were randomly assigned to two groups: Group A patients who underwent a 'traditional technique' to approach fused fissures and Group B patients who underwent a 'fissureless technique'. The latter technique avoids dissecting the lung parenchyma over the pulmonary artery, reducing the chances of air leak. Patients in both groups had shown no significant difference in preoperative variables (p>0.05). RESULTS: The incidence of PAL was significantly higher among patients with incomplete or fused fissures (0 case vs 8 cases (Groups A and B), p<0.005). Furthermore, the incidence of PAL was significantly higher in the Group A (traditional technique) (7 vs 1) (p<0.05, OR=3.1, CI 0.22-0.51). The probability for air leak cessation was significantly higher in patients of Group B (fissureless technique) (log rank p<0.0001). The length of hospital stay was higher in Group A (5.76+/-3.1) compared with Group B (4.9+/-1.7) (p<0.05). No other variables were identified as risk factors for PAL in this series. CONCLUSIONS: The fissureless technique appears to be a superior approach for fused fissures in terms of both preventing persistent air leak and reducing the length of hospitalisation. This technique can be performed safely at no additional cost and without adverse consequences.

Prevalence and Associated Factors of Insulin Resistance in Adults from Maracaibo City, Venezuela.

Background and Aim. Insulin resistance (IR) is a prominent pathophysiologic component in a myriad of metabolic disorders, including obesity, prediabetes, and type 2 diabetes mellitus, which are common in our locality. The objective of this study was to determine the prevalence of IR and factors associated with this condition in an adult population from Maracaibo city, Venezuela. Methodology. A cross-sectional, descriptive study with multistaged randomized sampling was carried out in 2026 adults. IR was defined as HOMA2-IR ≥ 2. A multiple logistic regression model was constructed in order to evaluate factors associated with IR. Results. The prevalence of IR was 46.5% (n = 943), with 46.7% (n = 450) in the general population, 46.4% (n = 493) in females, and 47.90% (n = 970) in males (p = 0.895). IR prevalence tended to increase with age and was significantly greater in subjects aged ≥30 years (χ (2) = 16.726; p = 2.33 × 10(-4)). Employment, alcohol consumption, obesity, high triacylglycerides, low HDL-C, and dysglycemia were associated with greater odds of IR, whereas a high level of physical activity appeared to be weak protective factor against IR. Conclusions. The prevalence of IR is elevated in our locality. The main determinants of this condition appear to be the presence of obesity, high triacylglycerides, low HDL-C, dysglycemia, and alcohol intake.

Massive hemoptysis caused by tracheal hemangioma treated with interventional radiology.

Capillary hemangiomas of the tracheobronchial tree are extremely rare in adults, with hemoptysis being one of the most serious forms of presentation. An operation has been the treatment of choice, although it does involve high rates of morbidity and mortality, especially in emergency situations such as massive hemoptysis, which has led to the search for other therapeutic alternatives. There is no experience with embolization by interventional radiology when the hemoptysis is tracheal in origin, caused partly because the infrequency of this pathology; however, the foundations for it have been laid with the development of embolization for bronchopulmonary pathology. We report a case of a tracheal capillary hemangioma in a 66-year-old woman diagnosed with idiopathic thrombopenic purpura, which began as a massive hemoptysis and was treated successfully with embolization by interventional radiology. There has been no recurrence of the bleeding after 1 year's follow-up, and the patient's control fibrobronchoscopy is normal.

Non-neoplastic mediastinal cysts.

OBJECTIVE: The non-neoplastic mediastinal cysts (NNMCs) form a group of uncommon benign lesions of a congenital origin. The significant controversy regarding these cysts is whether to manage with observation or surgical resection. The aim of this study is to analyse the utility of thoracic computed axial tomography (CT) in imaging diagnosis of the NNMCs and the results of surgery in these lesions. PATIENTS AND METHODS: Twenty NNMCs underwent surgery between 1980 and 2000. The preoperative study of mediastinal cystic masses includes a complete blood test, chest radiography (CR) and, for the last 15 years, a thoracic CT and/or nuclear magnetic resonance. All the patients underwent surgery in our thoracic surgery department and were reviewed in outpatients at 1 month, 6 months, 1 year and biannually thereafter. The form of manifestation, clinical features, imaging techniques, surgical operation, morbidity, mortality and follow-up are analysed. RESULTS: Ten corresponded to bronchogenic cysts, the most common symptom of which was chest pain. CR showed a mass in the anterior-superior mediastinum in nine cases, and CT (five cases) revealed a cystic tumour in the anterior mediastinum. All were removed surgically, with three patients presenting with mild complications. Seven corresponded to pleuro-pericardial cysts, four being asymptomatic. CR showed a right paracardial mediastinal tumour, which was confirmed by CT (four cases). All were removed surgically, with two patients presenting with mild complications. Three corresponded to enteric cysts. CR showed a tumour in the posterior mediastinum, with CT confirming its cystic nature (two cases). Excision of the cyst was done in all cases, which corresponded to duplication cysts: two oesophageal and one gastric. All the patients are asymptomatic and recurrence-free after a follow-up of 11 +/- 10 years. CONCLUSIONS: NNMCs are benign lesions in which the lesions in which the surgery can be done with a low morbidity and mortality rate, enables us to rule out malignancy and offers a definitive cure. Actually the thoracic CT permit a correct diagnosis pre-surgery in function of the radiologic characterisation and topography.

[Primary non-lymphoid thymic neoplasms. A study of 58 cases]. / Neoplasias primarias del timo de estirpe no linfoide. Estudio de 58 casos.

BACKGROUND AND OBJECTIVE: Primary non-lymphoid thymus tumors (PNLTT) are an uncommon though quite varied pathology. Our objective was to identify the clinical, therapeutic and histologic variables with a prognostic value in these neoplasms. PATIENTS AND METHOD: We studied 58 PNLTT cases, corresponding to 52 epithelial neoplams (PTEN), 4 thymolipomas (7%) and 2 neuroendocrine tumors (3%). Commonest clinical manifestations were myasthenia gravis (41%) and dyspnea (21%). Three patients were symptom-free (24%). We used Kaplan-Meier survival curves and Cox regression model. RESULTS: All patients underwent surgery which consisted of thymectomy. Four patients underwent a biopsy procedure alone. Perioperative mortality was 3% (n = 2) and morbidity was 31% (n = 18), mainly because of respiratory and wound problems. 24 patients with PTEN, Masaoka degrees III and IV, and a patient with a lymphoepithelial carcinoma received adjuvant chemotherapy and/or radiotherapy. With a follow-up of 13 + 5 years, 12 PTEN patients and one patient with a neuroendrocrine tumor died as a consequence of the evolution of the disease. Cumulative survival was 80% at 5 years, 71% at 7 years and 63% at 10 years. There are currently two local relapses in two PTEN cases after 9 and 8 years of follow-up, respectively. Main prognostic factors are the histologic type and subtype and the clinical stage (p < 0.001). CONCLUSIONS: In PNLTT early diagnosis is crucial in order to administer a correct treatment before the clinical stage is more advanced. Main prognostic factors are the histologic type and subtype and the clinical stage.

[Early detection of hypomania episodes in patients with affective disorder]. / Detección precoz de episodios de hipomanía en pacientes con trastorno afectivo.

INTRODUCTION: Bipolar disorder (BP) is one of the major causes of disability in the world. Epidemiological studies suggest that this disorder could be under-diagnosed owing to the difficulty in detecting hypomania episodes. The detection of present and past episodes of hypomania could help in the diagnosis and appropriate treatment of this disorder. The Hypomania Check List (HCL-32) is a questionnaire validated into Spanish and designed to detect past and present hypomania episodes in the psychiatric patient population. MATERIAL AND METHODS: A total of 128 patients over 18 years old and diagnosed with type I bipolar (BP-I) disorder (n=1), type II bipolar (BP-II) disorder (n=30), major depression (MD) (n=57), anxiety disorders (AD) (n=15) were selected, along with a control group (C) (n=25). The patients were diagnosed according to the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IVTR). Screening for hypomania episodes was carried out by applying the HCL-32 scale. RESULTS: The area under the ROC curve was 0.65 with a 95% confidence interval (CI) of 0.55-0.75. The chosen cut-off point of the HCL-32 was 15. The values for the sensitivity (Se), specificity (Sp), positive predictive values (PPV) and negative predictive values (NPV), and the prevalence (P) of hypomania episodes in the patients of the UP depression, for a cut-off point of 15 were: Se =71.4%, 95% CI; 57.8, 85.1, Sp =45.8%, 95% CI; 34.5-57.1, PPV=43.75%, 95% CI; 32.25-55.25), NPV:73.08%, 95% CI; 60.06-86.09) and P=67.2%. CONCLUSIONS: The HCL-32 is a very sensitive, but not very specific, screening tool. This could partly explain the high proportion of hypomania episodes detected in our sample. Unlike previous studies, our sample is heterogeneous (from different environments) and at a more severe and unstable clinical level. Future research should develop more specific measuring tools, and with greater external validation, for hypomania episodes.