Association of tyrosine hydroxylase 01 (TH01) microsatellite and insulin gene (INS) variable number of tandem repeat (VNTR) with type 2 diabetes and fasting insulin secretion in Mexican population.

PURPOSE: A variable number of tandem repeats (VNTR) in the insulin gene (INS) control region may be involved in type 2 diabetes (T2D). The TH01 microsatellite is near INS and may regulate it. We investigated whether the TH01 microsatellite and INS VNTR, assessed via the surrogate marker single nucleotide polymorphism rs689, are associated with T2D and serum insulin levels in a Mexican population. METHODS: We analyzed a main case-control study (n = 1986) that used univariate and multivariate logistic regression models to calculate the risk conferred by TH01 and rs689 loci for T2D development; rs689 results were replicated in other case-control (n = 1188) and cross-sectional (n = 1914) studies. RESULTS: TH01 alleles 6, 8, 9, and 9.3 and allele A of rs689 were independently associated with T2D, with differences between sex and age at diagnosis. TH01 alleles with ≥ 8 repeats conferred an increased risk for T2D in males compared with ≤ 7 repeats (odds ratio, ≥ 1.46; 95% confidence interval, 1.1-1.95). In females, larger alleles conferred a 1.5-fold higher risk for T2D when diagnosed ≥ 46 years but conferred protection when diagnosed ≤ 45 years. Similarly, rs689 allele A was associated with T2D in these groups. In males, larger TH01 alleles and the rs689 A allele were associated with a significant decrease in median fasting plasma insulin concentration with age in T2D cases; the reverse occurred in controls. CONCLUSION: Larger TH01 alleles and rs689 A allele may potentiate insulin synthesis in males without T2D, a process disabled in those with T2D.

Systemic bevacizumab as adjuvant therapy for recurrent respiratory papillomatosis in children: A series of three pediatric cases and literature review.

Recurrent respiratory papillomatosis (RRP), a viral disease caused by human papillomavirus (HPV), is the most common benign neoplasm of the larynx among children and the second most frequent cause of infantile hoarseness. The course of the disease is variable; some patients experience spontaneous remission, while others may develop an aggressive respiratory compromise. Especially juvenile-onset RRP cases experience shorter intervals between surgical interventions and thus more surgeries overall, causing high rates of depression and voice-related quality of life. Various local adjuvant therapies have been studied with mixed efficacy and some early potential but have failed to show consistent effect across large cohorts of patients. Bevacizumab, a recombinant monoclonal antibody that inhibits VEGF, has shown efficacy in patients with rapid regrowth of papillomas with severe airway compromise, and/or distal multisite spread of disease. We present three juvenile-onset RRP cases successfully managed with systemically administered bevacizumab.

Preparation of Peppermint Oil-Based Nanodevices Loaded with Paclitaxel: Cytotoxic and Apoptosis Studies in HeLa Cells.

In this work, several normal, oil-in-water (o/w) microemulsions (MEs) were prepared using peppermint essential oil, jojoba oil, trans-anethole, and vitamin E as oil phases to test their capacity to load paclitaxel (PTX). Initially, pseudo-ternary partial phase diagrams were constructed in order to find the normal microemulsion region using d-α-tocopherol polyethylene glycol 1000 succinate (TPGS-1000) as surfactant and isobutanol (iso-BuOH) as co-surfactant. Selected ME formulations were loaded with PTX reaching concentrations of 0.6 mg mL-1 for the peppermint oil and trans-anethole MEs, while for the vitamin E and jojoba oil MEs, the maximum concentration was 0.3 mg mL-1. The PTX-loaded MEs were stable according to the results of heating-cooling cycles and mechanical force (centrifugation) test. Particularly, drug release profile for the PTX-loaded peppermint oil ME (MEPP) showed that ∼ 90% of drug was released in the first 48 h. Also, MEPP formulation showed 70% and 90% viability reduction on human cervical cancer (HeLa) cells after 24 and 48 h of exposure, respectively. In addition, HeLa cell apoptosis was confirmed by measuring caspase activity and DNA fragmentation. Results showed that the MEPP sample presented a major pro-apoptotic capability by comparing with the unloaded PTX ME sample.

Pressure-induced amorphization of YVO4:Eu³âº nanoboxes.

A structural transformation from the zircon-type structure to an amorphous phase has been found in YVO4:Eu(3+) nanoboxes at high pressures above 12.7 GPa by means of x-ray diffraction measurements. However, the pair distribution function of the high-pressure phase shows that the local structure of the amorphous phase is similar to the scheelite-type YVO4. These results are confirmed both by Raman spectroscopy and Eu(3+) photoluminescence which detect the phase transition to a scheelite-type structure at 10.1 and 9.1 GPa, respectively. The irreversibility of the phase transition is observed with the three techniques after a maximum pressure in the upstroke of around 20 GPa. The existence of two (5)D0-->(7)F0 photoluminescence peaks confirms the existence of two local environments for Eu(3+), at least for the low-pressure phase. One environment is the expected for substituting Y(3+) and the other is likely a disordered environment possibly found at the surface of the nanoboxes.

Unusual records of deepwater teleosteans trawled off the western coast of Mexico.

The first records of three midwater species for the Mexican ichthyofauna (Holtbyrnia laticauda, Brama dussumieri and Cubiceps baxteri), caught off the coast of Baja California, Mexico, in mid 2014, are reported. As far as is known, they are the first verified specimens, geo-referenced and catalogued in a reference fish collection for the west coast of Mexico. The species' known distributions were extended northward in the eastern Pacific Ocean, ranging from 3495 to 8300 km.

Oncological outcome following anastomotic leak in rectal surgery.

BACKGROUND: The influence of anastomotic leak on local recurrence and survival remains debated in rectal cancer. METHODS: This was a multicentre observational study using data from the Spanish Rectal Cancer Project database. Demographics, American Society of Anesthesiologists classification, tumour location, stage, use of defunctioning stoma, administration of neoadjuvant and adjuvant treatment, invasion of circumferential resection margin, quality of mesorectal excision and anastomotic leakage were recorded. Anastomotic leak was defined as an anastomotic event requiring surgical intervention or interventional radiology, including pelvic abscesses without radiological evidence of leakage and early rectovaginal fistulas. Variables associated with oncological outcome were assessed by multivariable Cox regression analysis. RESULTS: A total of 1181 consecutive patients were included. Rates of anastomotic leak and 30-day postoperative mortality were 9·4 and 2·4 per cent respectively. Data from 1153 patients were analysed after a median follow-up of 5 years. Cumulative rates of local recurrence, overall recurrence, overall survival and cancer-specific survival were 4·9, 19·4, 77·5 and 84·7 per cent respectively. In the multivariable regression analysis, anastomotic leakage was not associated with local recurrence (hazard ratio (HR) 0·80, 95 per cent c.i. 0·28 to 2·26; P = 0·669), overall recurrence (HR 1·14, 0·70 to 1·85; P = 0·606), overall survival (HR 1·10, 0·73 to 1·65; P = 0·648) or cancer-specific survival (HR 1·23, 0·75 to 2·02; P = 0·421). CONCLUSION: Anastomotic leak after low anterior resection did not affect oncological outcomes in these patients.

Structural, elastic and vibrational properties of nanocrystalline lutetium gallium garnet under high pressure.

An ab initio study of the structural, elastic and vibrational properties of the lutetium gallium garnet (Lu3Ga5O12) under pressure has been performed in the framework of the density functional theory, up to 95 GPa. Pressure dependence of the elastic constants and the mechanical stability are analyzed, showing that the garnet structure is mechanically unstable above 87 GPa. Lattice-dynamics calculations in bulk at different pressures have been performed and compared with Raman scattering measurements of the nanocrystalline Tm(3+)-doped Lu3Ga5O12 up to 60 GPa. The theoretical frequencies and pressure coefficients of the Raman active modes for bulk Lu3Ga5O12 are in good agreement with the experimental data measured for the nano-crystals. The contributions of the different atoms to the vibrational modes have been analyzed based on the calculated total and partial phonon density of states. The vibrational modes have been discussed in relation to the internal and external modes of the GaO4 tetrahedron and the GaO6 octahedron. The calculated infrared modes and their pressure dependence are also reported. Our results show that with this nano-garnet size the sample has essentially bulk properties.

SPINK5 and ADRB2 haplotypes are risk factors for asthma in Mexican pediatric patients.

BACKGROUND: Asthma is one of the most common respiratory diseases worldwide, and the complexity of its etiology has been widely documented. Chromosome 5q31-33 is one of the main loci implicated in asthma and asthma-related traits. IL13, CD14 and ADRB2, which are located in this risk locus, are among the genes most strongly associated with asthma susceptibility. OBJECTIVES: This study evaluated whether single-nucleotide polymorphisms or haplotypes at 5q31-33 conferred risk for asthma in Mexican-Mestizo pediatric patients. METHODS: We performed a case-controlled study including 851 individuals, 421 of them affected with childhood-onset asthma and 430 ethnically matched unaffected subjects. We used the TaqMan Allelic Discrimination Assay to genotype 20 single-nucleotide polymorphisms within IL5, RAD50, IL13, IL4, CD14, SPINK5, HTR4, ADRB2 and IL12B. RESULTS: Although no association was detected for any risk allele, three SPINK5 haplotypes (GGCT: p = 6 × 10(-6); AATC: p = 0.0001; AGTT: p = 0.0001) and five ADRB2 haplotypes (AGGACC: p = 0.0014; AGGAAG: p = 0.0002; TGAGAG: p = 0.0001; AGGAAC: p = 0.0002; AAGGAG: p = 0.003) were associated with asthma. Notably, the AGTT SPINK5 haplotype exhibited a male gender-dependent association (p = 7.6 × 10(-5)). CONCLUSION: Our results suggest that SPINK5 and ADRB2 haplotypes might play a role in the susceptibility to childhood-onset asthma.

Multicentre propensity score-matched analysis of conventional versus extended abdominoperineal excision for low rectal cancer.

BACKGROUND: Abdominal perineal excision (APE) was originally described with levator ani removal for rectal cancer. An even wider, more aggressive extralevator resection for APE has been proposed. Although some surgeons are performing a very wide 'extralevator APE (ELAPE)', there are few data to recommend it routinely. This multicentre study aimed to compare outcomes of APE and ELAPE. METHODS: A multicentre propensity case-matched analysis comparing two surgical approaches (APE and ELAPE) was performed. All patients who underwent abdominoperineal resection of a rectal tumour were considered for the analysis. Tumour height was defined by magnetic resonance imaging measurement and patients with stage II-III tumours had neoadjuvant radiochemotherapy. Involvement of the circumferential resection margin (CRM) and intraoperative tumour perforation were the main outcome measures. A logistic regression model was used to study the relationship between the surgical approaches and outcomes. RESULTS: From January 2008 to March 2013 a total of 1909 consecutive patients underwent APE or ELAPE, of whom 914 matched patients (457 in each group) formed the cohort for analysis. Intraoperative tumour perforation occurred in 7.9 and 7.7 per cent of patients during APE and ELAPE respectively (P = 0.902), and there was CRM involvement in 13.1 and 13.6 per cent (P = 0.846). There were no differences between APE and ELAPE in terms of postoperative complication rates (52.3 versus 48.1 per cent; P = 0.209), need for reoperation (7.7 versus 7.0 per cent; P = 0.703), perineal wound problems (26.0 versus 21.9 per cent; P = 0.141), mortality rate (2.0 versus 2.0 per cent; P = 1.000) and local recurrence rate at 2 years (2.7 versus 5.6 per cent; P = 0.664). CONCLUSION: ELAPE does not improve rates of CRM involvement, intraoperative tumour perforation, local recurrence or mortality.

Pharmacological treatments for the correction of presbyopia.

Presbyopia affects between 1.7 and 2 billion people worldwide. Presbyopia significantly impacts productivity and quality of life in both developed and developing countries. During accommodation, the human eye changes its dioptric power by altering the shape of the lens, but the exact nature of this change has not been fully explained. Recently, topical treatments have been marketed for the treatment of presbyopia and others are under investigation. In order to prepare a review of these novel therapies, we searched the major biomedical search engines. We found 15 randomized clinical trials and 12 reviews that met our review criteria. There are two different strategies for this purpose, the pinhole effect that increases depth of focus and "crystalline lens relaxation" for which parasympathetic mimetics and lens oxidation intermediates have been used. The results are generally favorable in terms of improvement of near visual acuity, although the follow-up period of the studies is short. These are novel strategies in the early stages of research that could be useful in the treatment of presbyopia.

Iatrogenic affectation of ocular motility by immune checkpoint inhibitors.

Cancer therapy relies on new antitumoral drugs called immune checkpoint inhibitors (ICI), which produce long-lasting anti-tumor responses and lengthen survival, but cause autoimmune-type toxicity. The clinical characteristics induced by ICI are not well characterized to date and careful collection of clinical data is required to accurately define its safety profile. We conducted a literature search in the main clinical search engines to identify pharmacological ocular iatrogenic events of ICIs related to ocular motility. Four systematic reviews were found that included this type of ocular iatrogenesis as well as numerous isolated case reports. Reported adverse effects include: oculomotor paresis, optic neuropathy, optic atrophy, myastheniform syndromes, thyroid pseudo-orbitopathy, orbital apex syndrome, and hypophysitis. Most were managed without interruption or with partial interruption of cancer treatment. Aggressive systemic treatments were required for adequate management of ocular iatrogenic events. It is essential that the ophthalmologist become familiar with the new ICI oncological treatments, capable of causing severe and disabling motilidad ocular iatrogenesis for the patient. The communication of adverse effects and the report of the treatments used can help the most appropriate management of these patients. Research should be oriented towards complex differential diagnosis and to optimize decisions on cancer treatments.

Neural response to the observable self in social anxiety disorder.

BACKGROUND: Distorted images of the observable self are considered crucial in the development and maintenance of social anxiety. We generated an experimental situation in which participants viewed themselves from an observer's perspective when exposed to scrutiny and evaluation by others. Method Twenty patients with social anxiety disorder (SAD) and 20 control subjects were assessed using functional magnetic resonance imaging (fMRI) during the public exposure of pre-recorded videos in which they were each shown performing a verbal task. The examiners acted as the audience in the experiment and rated performance. Whole-brain functional maps were computed using Statistical Parametric Mapping. RESULTS: Robust activation was observed in regions related to self-face recognition, emotional response and general arousal in both study groups. Patients showed significantly greater activation only in the primary visual cortex. By contrast, they showed significant deactivation or smaller activation in dorsal frontoparietal and anterior cingulate cortices relevant to the cognitive control of negative emotion. Task-related anxiety ratings revealed a pattern of negative correlation with activation in this frontoparietal/cingulate network. Importantly, the relationship between social anxiety scores and neural response showed an inverted-U function with positive correlations in the lower score range and negative correlations in the higher range. CONCLUSIONS: Our findings suggest that exposure to scrutiny and evaluation in SAD may be associated with changes in cortical systems mediating the cognitive components of anxiety. Disorder severity seems to be relevant in shaping the neural response pattern, which is distinctively characterized by a reduced cortical response in the most severe cases.

Impact of a multidisciplinary team training programme on rectal cancer outcomes in Spain.

AIM: The Spanish Rectal Cancer Project was established in 2006, inspired by the Norwegian Rectal Cancer Project. It consisted of an educational project aiming to introduce mesorectal excision surgery to surgeons, pathologists and radiologists. Its effect on local recurrence (LR) was compared with the Norwegian Project. METHOD: An observational cohort study was carried out including all patients (4700) with rectal cancer from a population of 19 329 992 inhabitants operated on in 51 Spanish hospitals between March 2006 and June 2010. Curative resection was defined as a resection with an uninvolved circumferential margin in patients without distant metastases and without intra-operative rectal perforation. The effectiveness of the programme was measured by a central registry with feedback to participating institutions of their own results compared with the national average. The main outcome measures were LR and adverse effects in curative resections. RESULTS: Of the 4700 patients, 3213 had a resection considered to be curative. LR rates were 4.7% (95% CI 0.03-0.59), metastasis rate was 16% (95% CI 0.14-0.17) and overall survival was 87.8% (95% CI 0.86-0.89). Multivariate analysis showed that advanced TNM stage and decreasing distance of the tumour from the anal verge had a negative influence on LR. CONCLUSION: This study shows that the results obtained in Norway have been reproduced in a larger population in Spain applying a similar methodology.

Laparoscopic versus open surgery for rectal cancer: results of a prospective multicentre analysis of 4,970 patients.

OBJECTIVE: To compare laparoscopic versus open surgery for rectal cancer and analyse the results of the multidisciplinary audited project on total mesorectal excision conducted in Spain. BACKGROUND: The safety and therapeutic efficiency of laparoscopic surgery for rectal cancer are controversial due to the technical difficulties it involves. A deviation from the oncological principles of mesorectal excision would mean a potential increase in local recurrence and shorter survival. METHODS: This prospective non-randomised multicentre study includes 4,970 patients with rectal cancer. The study compares perioperative, postoperative, anatomicopathological and survival variables. RESULTS: Five hundred and sixty five patients were excluded. Of the remaining 4,405, 3,018 (68.51%) had open surgery (OS) and 1,387 (31.49%) laparoscopic surgery (LS). The rate of anterior resections was higher in the LS group. The rate of intraoperative tumour perforation, number of red blood cell concentrates transfused and length of hospital stay were greater in the OS group, whereas surgical time was longer in the LS group. The incidence of complications was 45.6% in the OS group and 38.3% in the LS group. Involvement of the circumferential and distal margin, as well as unsatisfactory and partially satisfactory quality of the mesorectum, were greater in the OS group. There were no differences for local recurrence and survival rates. CONCLUSIONS: According to these results, laparoscopic surgery is the best option for the surgical treatment of rectal cancer, with similar rates of local recurrence and survival, although there are oncological indicators in this study to suggest that these results can be improved with laparoscopic surgery.

Surgical training with phantoms in strabismus surgery.

BACKGROUND AND PURPOSE: Simulation in surgical learning responds to ethical and pragmatic needs. Our purpose is to describe the effects on surgical skills of conducting a surgical training workshop on strabismus surgery with phantoms. Concern for patient safety makes it necessary to consider the use of simulators (virtual and three-dimensional physical) and animal models that allow the applicant to safely practice the procedures before facing a real case. MATERIAL AND METHODS: Realization of a workshop with previous theoretical content and real practice with phantoms designed to simulate strabismus surgery (eyeball, 6 muscles, conjunctiva, eyelid and tenon capsule inserted in the skull) of real anatomical dimensions. Satisfaction survey and subjective evaluation of learning by the student and the expert tutor according to the Kirkpatrick evaluation model. RESULTS: Total, 100% of the 26 students attending two courses (15 students in one course and 11 students in another course) and 100% of the 3 tutors who participated in both courses completed the survey. 20 were resident doctors and 20 specialists in ophthalmology. The overall satisfaction of the students was 8.2 (±0.68). CONCLUSIONS: According to the results of the Kirkpatrick training actions evaluation survey, the perception of students and tutors is that training with phantoms in strabismus surgery can help improve the skills necessary for safe and independent practice. The ultimate goal being to improve patient safety.

European quality assurance programme in rectal cancer--are we ready to launch?

AIM: There have been initiatives to create a European audit project. This paper addresses the issue of differences in data collected by different registries. METHOD: Patients with rectal cancer treated in 2008 and recorded in quality registries from Belgium, Germany/Poland, Spain and Sweden were analyzed. The comparison included number of patients, gender, age, American Society of Anesthesiology (ASA) classification, preoperative diagnostic and staging procedures, neoadjuvant therapy, surgical treatment and quality of surgery, postoperative complications and adjuvant treatment. RESULTS: The Belgian database consisted of 622 patients, the German/Polish database consisted of 3,393 patients, the Spanish database consisted of 1,641 patients and the Swedish database consisted of 1,826 patients. The percentage of patients in each ASA stage was highly variable. MRI use was highest in Spain and Sweden and very low in Germany/Poland. The percentage of cT4 stage tumours in Sweden was much higher than in all other countries. Sweden recorded the highest percentage of primary metastatic disease (20.3%) and Belgium recorded the lowest (10.2%). Neoadjuvant therapy in different protocols was administered to 41.2% patients in Germany/Poland, to 50.8% in Spain, to 55.2% in Belgium and to 62% in Sweden. Laparoscopic surgery (conversion rate) was performed for cure in 5% (28%) of patients in Sweden, in 20.8% (20.6%) in Spain, in 28.6% (15.2%) in Belgium and in 14.5% (8.9%) in Germany/Poland. The 30-day mortality for anterior resection, abdominoperineal excision and Hartmann's procedure in Sweden, Belgium and Spain was 2.0%, 2.3% and 3.1%, respectively. The German/Polish database reported an in-hospital mortality of 3.2%. CONCLUSION: A European quality assurance project in rectal cancer is possible only after data collection is standardized.

Risk factors for surgical site infection after elective resection for rectal cancer. A multivariate analysis on 2131 patients.

AIM: Surgical site infection (SSI) is the most common cause of morbidity after colorectal surgery. The aim of this study was to analyze risk factors for SSI in patients who had undergone surgery for rectal cancer. METHOD: A multicentre observational study was carried out on 2131 patients operated on for rectal cancer between May 2006 and May 2009. Twenty-nine centres were involved. SSI included wound infection and organ space infection within 30 days after the operation. Univariate and multivariate analyses were carried out to study possible risk factors for SSI. RESULTS: Wound infection and organ space infection were diagnosed in 8.9% and 10%, respectively, of patients. The anastomotic leakage rate was 8%. Multivariate analysis showed that wound infection was related to tumour stage, a converted laparoscopic procedure and open surgery. Organ space infection was related to Stage IV tumour, a tumour < 11 cm from the anal verge, low anterior resection and Hartmann's procedure. CONCLUSION: Rectal surgery for malignant disease is associated with a considerable rate of SSI. Wound infection and organ space infection are related to different factors and therefore should be evaluated separately.

Polyuria in adults. A diagnostic approach based on pathophysiology.

Polyuria is a common clinical condition characterized by a urine output that is inappropriately high (more than 3 L in 24 h) for the patient's blood pressure and plasma sodium levels. From a pathophysiological point of view, it is classified into two types: polyuria due to a greater excretion of solutes (urine osmolality >300 mOsm/L) or due to an inability to increase solute concentration (urine osmolality <150 mOsm/L). Sometimes both mechanisms can coexist (urine osmolality 150-300 mOsm/L). Polyuria is a diagnostic challenge and its proper treatment requires an evaluation of the medical record, determination of urine osmolality, estimation of free water clearance, use of water deprivation tests in aqueous polyuria, and measurement of electrolytes in blood and urine in the case of osmotic polyuria.

Antimicrobial cotton gauzes modified with poly(acrylic acid-co-maltodextrin) hydrogel using chitosan as crosslinker.

Cotton gauzes were grafted with a hydrogel of maltodextrin (MD) and poly(acrylic acid) (PAAc) using N-maleyl chitosan as crosslinker to obtain materials with antimicrobial properties. Reaction parameters including monomer, crosslinker, and initiator concentrations were studied. The modification with the copolymer poly(acrylic acid)-co-maltodextrin (PAAc-co-MD) was corroborated by Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). The grafted gauzes (gauze-g-(PAAc-co-MD)) were able to load vancomycin and inhibit the growth of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria. In addition, the incorporation of chitosan as crosslinker showed a synergistic effect against these bacteria. The prepared gauze-g-(PAAc-co-MD) materials could be used in the biomedical area particularly as antimicrobial wound dressings.