A single oscillating proto-hypothalamic neuron gates taxis behavior in the primitive chordate Ciona.

Ciona larvae display a number of behaviors, including negative phototaxis. In negative phototaxis, the larvae first perform short spontaneous rhythmic casting swims. As larvae are cast in a light field, their photoreceptors are directionally shaded by an associated pigment cell, providing a phototactic cue. This then evokes an extended negative taxis swim. We report here that the larval forebrain of Ciona has a previously uncharacterized single slow-oscillating inhibitory neuron (neuron cor-assBVIN78) that projects to the midbrain, where it targets key interneurons of the phototaxis circuit known as the photoreceptor relay neurons. The anatomical location, gene expression, and oscillation of cor-assBVIN78 suggest homology to oscillating neurons of the vertebrate hypothalamus. Ablation of cor-assBVIN78 results in larvae showing extended phototaxis-like swims, even in the absence of phototactic cues. These results indicate that cor-assBVIN78 has a gating activity on phototaxis by projecting temporally oscillating inhibition to the photoreceptor relay neurons. However, in intact larvae, the frequency of cor-assBVIN78 oscillation does not match that of the rhythmic spontaneous swims, indicating that the troughs in oscillations do not themselves initiate swims but rather that cor-assBVIN78 may modulate the phototaxis circuit by filtering out low-level inputs while restricting them temporally to the troughs in inhibition.

Toll-like receptor 2-modulating pectin-polymers in alginate-based microcapsules attenuate immune responses and support islet-xenograft survival.

Encapsulation of pancreatic islets in alginate-microcapsules is used to reduce or avoid the application of life-long immunosuppression in preventing rejection. Long-term graft function, however, is limited due to varying degrees of host tissue responses against the capsules. Major graft-longevity limiting responses include inflammatory responses provoked by biomaterials and islet-derived danger-associated molecular patterns (DAMPs). This paper reports on a novel strategy for engineering alginate microcapsules presenting immunomodulatory polymer pectin with varying degrees of methyl-esterification (DM) to reduce these host tissue responses. DM18-pectin/alginate microcapsules show a significant decrease of DAMP-induced Toll-Like Receptor-2 mediated immune activation in vitro, and reduce peri-capsular fibrosis in vivo in mice compared to higher DM-pectin/alginate microcapsules and conventional alginate microcapsules. By testing efficacy of DM18-pectin/alginate microcapsules in vivo, we demonstrate that low-DM pectin support long-term survival of xenotransplanted rat islets in diabetic mice. This study provides a novel strategy to attenuate host responses by creating immunomodulatory capsule surfaces that attenuate activation of specific pro-inflammatory immune receptors locally at the transplantation site.

Latin American Clinical Practice Guidelines on the Systemic Treatment of Psoriasis SOLAPSO - Sociedad Latinoamericana de Psoriasis (Latin American Psoriasis Society).

This Clinical Practice Guideline on the systemic treatment of Psoriasis includes the recommendations elaborated by a panel of experts from the Latin American Psoriasis Society SOLAPSO, who assessed the quality of the available evidence using the GRADE system and the PICO process to guide the literature search. To answer each question, the experts discussed the results of randomized controlled trials, observational studies and metanalysis evaluating the interventions identified (non-biologics, biologics and phototherapy) in different populations of patients with moderate to severe plaque-psoriasis, which was summarized in Tables ad-hoc. The main end-points considered to assess efficacy were PASI 50, 75, 90 and 100, PGA 0-1 and significant improvement of health-related quality of life. Specific adverse events, either severe or leading to treatment interruption, were also evaluated. The 31 recommendations included in this CPG follow the structure proposed by GRADE: direction (for or against) and strength (strong or weak). The goal of this CPG is to improve the management of patients with psoriasis by recommending interventions of proved benefit and providing a reference standard for the treating physician. Adhering to the contents of this CPG does not guarantee therapeutic success. The final decision on the specific treatment is the responsibility of the physician based on the individual circumstances and considering the values, the preferences and the opinions of the patient or caregivers.

Latin American Clinical Practice Guidelines on the systemic treatment of psoriasis: SOLAPSO ­ Sociedad Latinoamericana de Psoriasis (Latin American Psoriasis Society)

This Clinical Practice Guideline on the systemic treatment of Psoriasis includes the recommendations elaborated by a panel of experts from the Latin American Psoriasis Society SOLAPSO, who assessed the quality of the available evidence using the GRADE system and the PICO process to guide the literature search. To answer each question, the experts discussed the results of randomized controlled trials, observational studies and metanalysis evaluating the interventions identified (non-biologics, biologics and phototherapy) in different populations of patients with moderate to severe plaque-psoriasis, which was summarized in Tables ad-hoc. The main end-points considered to assess efficacy were PASI 50, 75, 90 and 100, PGA 0-1 and significant improvement of healthrelated quality of life. Specific adverse events, either severe or leading to treatment interruption, were also evaluated. The 31 recommendations included in this CPG follow the structure proposed by GRADE: direction (for or against) and strength (strong or weak). The goal of this CPG is to improve the management of patients with psoriasis by recommending interventions of proved benefit and providing a reference standard for the treating physician. Adhering to the contents of this CPG does not guarantee therapeutic success. The final decision on the specific treatment is the responsibility of the physician based on the individual circumstances and considering the values, the preferences and the opinions of the patient or caregivers.

Comparisons of the spectroscopic and microbiological activities among coumarin-3-carboxylate, o-phenanthroline and zinc(II) complexes.

Coumarins (2H-chromen-2-one) are oxygen-containing heterocyclic compounds that belong to the benzopyranones family. In this work we have synthesized different coordination complexes with coumarin-3-carboxylic acid (HCCA), o-phenanthroline (phen) and zinc(II). In the reported [Zn(CCA)2(H2O)2] complex, coumarin-3-carboxylate (CCA) is acting as a bidentate ligand while in the two prepared complexes, [Zn(phen)3]CCA(NO3) (obtained as a single crystal) and [Zn(CCA)2phen].4H2O, CCA is acting as a counterion of the complex cation [Zn(phen)3]+2 or coordinated to the metal center along with phen, respectively. These compounds were characterized on the basis of elemental analysis and thermogravimetry. NMR, FTIR and Raman spectroscopies of the compounds and the CCA potassium salt (KCCA) allow to determine several similarities and differences among them. Finally, their behavior against alkaline phosphatase enzyme and their antimicrobial activities were also measured.

A systematic review of the impact of mindfulness on the well-being of healthcare professionals.

OBJECTIVE: Among efforts to improve the well-being of healthcare professionals are initiatives based around mindfulness meditation. To understand the value of such initiatives, we conducted a systematic review of empirical studies pertaining to mindfulness in healthcare professionals. METHOD: Databases were reviewed from the start of records to January 2016. Eligibility criteria included empirical analyses of mindfulness and well-being outcomes acquired in relation to practice. 81 papers met the eligibility criteria, comprising a total of 3,805 participants. Studies were principally examined for outcomes such as burnout, distress, anxiety, depression, and stress. RESULTS: Mindfulness was generally associated with positive outcomes in relation to most measures (although results were more equivocal with respect to some outcomes, most notably burnout). CONCLUSION: Overall, mindfulness does appear to improve the well-being of healthcare professionals. However, the quality of the studies was inconsistent, so further research is needed, particularly high-quality randomized controlled trials.

Topical zoledronic acid decreases micromotion induced bone resorption in a sheep arthroplasty model.

BACKGROUND: Initial micromotion of a total hip replacement is associated with aseptic loosening. The use of bisphosphonates could be one way to reduce peri-implant bone resorption induced by micromotion. Bisphosphonates compounds are inhibitors of bone resorption. The aim of this study was to investigate whether local treatment with bisphosphonate would reduce bone resorption and fibrous tissue around an experimental implant subjected to micromotion. METHODS: One micromotion implant were inserted into each medial femoral condyle in ten sheep. During each gait cycle the implant axially piston 0.5 mm. During surgery one of the femoral condyles were locally treated with 0.8 mg zoledronate. The other condyle served as control. Observation period was 12 weeks. RESULTS: Histological evaluation showed a fibrous capsule around both the control and bisphosphonate implants. Histomorphometrical analysis showed that 97% of the surface on both control and bisphosphonate implants were covered by fibrous tissue. However, the bisphosphonate was able to preserve bone in a 1 mm zone around the implants. CONCLUSION: This study indicates that local treatment with bisphosphonate cannot prevent the formation of a fibrous capsule around an implant subjected to micromotion, but bisphosphonate is able to reduce resorption of peri-prosthetic bone.

Sechium edule (Jacq.) Swartz, a New Cultivar with Antiproliferative Potential in a Human Cervical Cancer HeLa Cell Line.

The Sechium edule Perla Negra cultivar is a recently-obtained biological material whose progenitors are S. edule var. nigrum minor and S. edule var. amarus silvestrys, the latter of which has been reported to have antiproliferative activity against the HeLa P-388 and L-929 cancer cell lines. The present study aimed to determine if the methanolic extract of the fruit of the Perla Negra cultivar had the same biological activity. The methanolic extract was phytochemically characterized by thin layer chromatography (TLC) and column chromatography (CC), identifying the terpenes and flavonoids. The compounds identified via high performance liquid chromatography (HPLC) were Cucurbitacins B, D, E, and I for the terpene fractions, and Rutin, Phlorizidin, Myricetin, Quercetin, Naringenin, Phloretin, Apigenin, and Galangin for the flavonoid fractions). Biological activity was evaluated with different concentrations of the methanolic extract in the HeLa cell line and normal lymphocytes. The methanolic extract inhibited the proliferation of HeLa cells (IC50 1.85 µg·mL-1), but the lymphocytes were affected by the extract (IC50 30.04 µg·mL-1). Some fractions, and the pool of all of them, showed inhibition higher than 80% at a concentration of 2.11 µg·mL-1. Therefore, the biological effect shown by the methanolic extract of the Perla Negra has some specificity in inhibiting tumor cells and not normal cells; an unusual feature among molecules investigated as potential biomedical agents.

Theoretical investigation of the conformational space of baicalin.

Flavonoids are a large group of polyphenolic compounds ubiquitously present in plants. They are important components of human diet. They are recognized as potential drug candidates to be used in the treatment and prevention of a lot of pathological disorders, due to their protective effects. Baicalin (7-glucuronic acid 5, 6-dihydroxyflavone) is one of the main single active constituents isolated from the dried roots of Scutellaria baicalensis Georgi. The great interest on this flavonoid is due to its various pharmacological properties, such as antioxidant, antimicrobial, anti-inflammatory, anticancer and so on, and its high accumulation in the roots of S. baicalensis. The aim of our work was to analyze the geometric and electronic properties of baicalin conformers (BCL), thus performing a complete search on the conformational space of this flavonoid in gas phase and in aqueous solution. The results indicate that the conformational space of baicalin is formed by eight conformers in gas phase and five conformers in aqueous solution optimized at B3LYP/6-311++G** theory level. BCLa2TT and BCLa1TT conformers have low stability in gas phase and very high stability in aqueous solution. This variation is related to a modification in the τ1 angle that represents the relative position of the glucuronide unit respect to the central rings of the flavan nucleus (A and C). This modification was successfully explained by examining the changes in the hydrogen bond (HB) interactions that occur in the region around the hydroxyl group located in position 6 of ring A. Besides, the molecular electrostatic potential (MEP) and frontier molecular orbital (FMO) analyses indicate that BCLa2TT and BCLa1TT conformers are the most favorable conformers for interacting with positively charged species (such as metal ions) in aqueous media (such as biological fluids).

Evidence of promising biological-pharmacological activities of the sertraline-based copper complex: (SerH2)2[CuCl4].

In the current study the ability of copper complex to exert multiple biological activities is combined with the pharmacological action of sertraline (SerH2Cl, antidepressant drug). The hydrated and anhydrous forms of the tetrachlorocuprate(II) salts, namely (SerH2)2[CuCl4]·½H2O and (SerH2)2[CuCl4], were synthesized and characterized by physicochemical methods. The crystal structures were determined by X-ray diffraction methods. The hydrate complex crystallizes in the monoclinic P21 space group with a=8.0807(2) Å, b=36.2781(8) Å, c=12.6576(3) Å, ß=95.665(2)°, and Z=4 molecules per unit cell and the un-hydrate in P21 with a=13.8727(6) Å, b=7.5090(3) Å, c=18.618(1) Å, ß=104.563(6)°, and Z=2. It has been suggested that Cu(II) ions might be critical in the development of mood disorders, showed potent biocidal activity, and also acted as analgesic adjuvant. To improve sertraline efficiency, the antidepressant and analgesic activities of the complex have been assessed in rats denoting a marked synergistic effect. Antithyroid and antimicrobial activities were also evaluated. Because depressive disorders and hyperthyroidism diseases led to an oxidative stress state, antioxidant capability has also been tested. The complex behaved as a good superoxide radical scavenger (IC50=6.3×10-6M). The ability of the complex to act as bromoperoxidase mimic was assessed. A pseudo-first order constant of k=0.157±0.007min-1 has been determined. The complex evidences promising biological-pharmacological activities and the albumin binding studies showed a Kb of 2.90×103M-1 showing an improvement in the uptake of sertraline by albumin at 8h incubation (time required for effective interaction of sertraline with the protein).

HPLC-MS analysis of proanthocyanidin oligomers and other phenolics in 15 strawberry cultivars.

The phenolic compounds of 15 strawberry cultivars grown in Spain were analyzed and quantified: anthocyanins (20.2-47.4 mg/100 g of fw) (cyanidin 3-glucoside and pelargonidin 3-glucoside, 3-rutinoside, and 3-malonyl glucoside), flavonols (1.5-3.4 mg/100 g of fw) (quercetin 3-glucuronide and kaempferol 3-glucoside and 3-p-coumaroyl-glucoside), proanthocyanidins (53.9-163.2 mg/100 g), p-coumaroyl-glucose (0.84-6.70 mg/100 g), ellagitannins (9.67-22.86 mg/100 g) (sanguiin H-6, lambertianin C, and galloyl bis-HHDP-glucose), and ellagic acid glycosides (0.88-2.06 mg/100 g of fw) (two ellagic acid deoxyhexosides). Proanthocyanidins, the main phenolic compounds, were characterized by phloroglucinol degradation. Their mean degree of polymerization ranged from 3.4 for cv. Chiflon to 5.8 for cv. Ventana, the average value being 4.3. The terminal unit of proanthocyanidin oligomers was always (epi)catechin (17.36-29.93%) and (epi)catechin (61.66-75.39%) or (epi)afzelechin (4.50-10.54%) as extension units. Different combinations of (epi)catechin and (epi)afzelechin were detected, and their sequence of linkage was characterized by HPLC-MS-MS. Relative percentages of dimers, trimers, tetramers, and pentamers were evaluated by the extracted ion chromatogram (EIC) analysis.

Targeted expression of human serum albumin to potato tubers.

Complementary DNA expression of mature human serum albumin was engineered into potato plants under the transcriptional control of patatin B33 promoter and potato proteinase inhibitor II terminator. Protein secretion was achieved by using the signal sequence from potato proteinase inhibitor II. Recombinant albumin accumulated up to 0.2% of total soluble tuber protein in single transformant lines, regardless of the potato cultivar used. Electrophoretic mobility and N-terminal amino acid sequence analysis of partially purified recombinant albumin confirmed proper processing of an immune responsive recombinant albumin, and revealed that the proteinase inhibitor II signal sequence was correctly removed. No further optimisation of these yields was obtained by HSA expression in patatin antisense plants (line Pas58). Subcellular localisation showed that recombinant protein was successfully targeted to the apoplast. Potato tubers may be used, by applying this technology, to produce other heterologous proteins of interest in the biopharmaceutical industry.

Significancia pronóstica del tamaño tumoral en la sobrevida de pacientes con carcinoma gástrico avanzado / Pronostic significance of tumoral size in the survival of advanced gastric carcinoma

Objetivo: Determinar la significancia pronóstica del tamaño del tumor en la sobrevida de pacientes con carcinoma gástrico avanzado. Material y método: Este estudio retrospectivo evaluó 95 pacientes con adenocarcinoma gástrico avanzado con un diámetro menor de 7 centímetros (grupo I) y 85 casos con lesiones con diámetro mayor o igual a 7 centímetros (Grupo II), sometidos a gastrectomía radical con linfadenectomía DO-D1 (n igual 148) y linfadenectomía extendida D2-D3-D4 (N igual 32) en el Hospital Belén, Trujillo, Perú, entre 1966 y 1998. Resultados: la edad promedio del grupo I y II fue de 58.05 más menos 12.9 y 58.53 más menos 15.26 años, respectivamente. Los pacientes del grupo II tuvieron un menor nivel de hemoglobina sérica (p igual 0.007) y mayor frecuencia de lesiones tipo Borrmann III y IV (p igual 0.003), en comparación con el grupo I. Entre ambos grupos, usando el tst de log - rank, no se encontró diferencia estadísticamente significativa con relación a la sobrevida quinquenal (p mayor 0.05). Realizando el análisis multivariado de regresión de Cox, tampoco se encontró significancia estadística entre el tamaño tumoral y la sobrevida, pero fueron factores independientes estadísticamente relacionados con la sobrevida: profundidad de la invasión (p igual 0.017) y el estado ganglionar regional (p igual 0.014). Conclusiones: Clínicamente el tamaño del tumor no es un factor a tomar como parámetro en la predicción de la sobrevida actuarial en pacientes con cáncer gástrico avanzado.