Search

The spittlebug Philaenus spumarius (Hemiptera: Aphrophoridae) is the predominant vector of Xylella fastidiosa (Xanthomonadales: Xanthomonadaceae) in Apulia, Italy and the rest of Europe. Current control strategies of the insect vector rely on mechanical management of nymphal stages and insecticide application against adult populations. Entomopathogenic fungi (EPF) are biological control agents naturally attacking spittlebugs and may effectively reduce population levels of host species. Different experimental trials in controlled conditions have been performed to i) identify naturally occurring EPF on P, spumarius in Northwestern Italy, and ii) evaluate the potential for biocontrol of the isolated strains on both nymphal and adult stages of the spittlebug. Four EPF species were isolated from dead P. spumarius collected in semi-field conditions: Beauveria bassiana, Conidiobolus coronatus, Fusarium equiseti and Lecanicillium aphanocladii. All the fungal isolates showed entomopathogenic potential against nymphal stages of P. spumarius (≈ 45 % mortality), except for F. equiseti, in preliminary trials. No induced mortality was observed on adult stage. Lecanicillium aphanocladii was the most promising fungus and its pathogenicity against spittlebug nymphs was further tested in different formulations (conidia vs blastospores) and with natural adjuvants. Blastospore formulation was the most effective in killing nymphal instars and reducing the emergence rate of P, spumarius adults, reaching mortality levels (90%) similar to those of the commercial product Naturalis®, while no or adverse effect of natural adjuvants was recorded. The encouraging results of this study pave way for testing EPF isolates against P, spumarius in field conditions and find new environmentally friendly control strategies against insect vectors of X. fastidiosa., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Bosco Domenico reports financial support and equipment, drugs, or supplies were provided by Globachem Discovery Ltd, Bosco Domenico reports financial support was provided by Horizon Europe Food Bioeconomy Natural Resources Agriculture and Environment]., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Entomopathogenic ascomycetes (EA) are an important part of the microbiota in most terrestrial ecosystems, where they can be found regulating natural populations of arthropod pests in both epigeous and hypogeous habitats while also establishing unique relationships with plants. These fungi offer direct benefits to agriculture and human welfare. In the present work, we conducted a systematic review to comprehensively assess the range of ecosystem services provided by EA, including direct and indirect pest biocontrol, plant growth promotion, plant defense against other biotic and abiotic stresses, nutrient cycling, and the production of new bioactive compounds with agricultural, pharmaceutical and medical importance. Moreover, EA are compatible with the ecosystem services provided by other microbial and macrobial biocontrol agents. This systematic review identified the need for future research to focus on evaluating the economic value of the ecological services provided by EA with a special emphasis on hypocrealean fungi. This evaluation is essential not only for the conservation but also for better regulation and exploitation of the benefits of EA in promoting agricultural sustainability, reducing the use of chemicals that enter the environment, and minimizing the negative impacts of crop protection on the carbon footprint and human health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Previous studies have reported differences in the management and outcome of women stroke patients in comparison with men. We aim to analyze sex and gender differences in the medical assistance, access to treatment and outcome of acute stroke patients in Catalonia., Patients and Methods: Data were obtained from a prospective population-based registry of stroke code activations in Catalonia (CICAT) from January/2016 to December/2019. The registry includes demographic data, stroke severity, stroke subtype, reperfusion therapy, and time workflow. Centralized clinical outcome at 90 days was assessed in patients receiving reperfusion therapy., Results: A total of 23,371 stroke code activations were registered (54% men, 46% women). No differences in prehospital time metrics were observed. Women more frequently had a final diagnosis of stroke mimic, were older and had a previous worse functional situation. Among ischemic stroke patients, women had higher stroke severity and more frequently presented proximal large vessel occlusion. Women received more frequently reperfusion therapy (48.2% vs 43.1%, p  < 0.001). Women tended to present a worse outcome at 90 days, especially for the group receiving only IVT (good outcome 56.7% vs 63.8%; p  < 0.001), but not for the group of patients treated with IVT + MT or MT alone, although sex was not independently associated with clinical outcome in logistic regression analysis (OR 1.07; 95% CI, 0.94-1.23; p  = 0.27) nor in the analysis after matching using the propensity score (OR 1.09; 95% CI, 0.97-1.22)., Discussion and Conclusion: We found some differences by sex in that acute stroke was more frequent in older women and the stroke severity was higher. We found no differences in medical assistance times, access to reperfusion treatment and early complications. Worse clinical outcome at 90 days in women was conditioned by stroke severity and older age, but not by sex itself.

The university stage is a good time to promote healthy eating strategies. The sociological and cultural changes experienced by students lead them to skip meals, increase their intake of fast food and energy-dense foods, decreasing adherence to the Mediterranean diet (MD). Professionals related to food such as nutritionists and dietitians are also considered a population at risk of developing eating disorders due to the extensive knowledge they possess, which can be used for both good and bad practice. The objective was to analyze the impact of a 4-month educational program promoting the Mediterranean diet on risky eating behaviors, adherence to the Mediterranean diet, and body composition in nutrition and dietetics students, studying the differences according to the group investigated (control group and educated group). The context of the research was 196 students (49 males and 147 females) from two consecutive years. The control group did not receive any type of intervention, while with the control group (educated) an educational program was carried out. Results showed that women with greater control over energy intake, carbohydrates, and sugar had a lower percentage of fat mass, while in men, the relationship was established with weight. Regarding adherence to the Mediterranean diet, at post, it is adequate in both men (8.25 ± 2.87) and women (7.90 ± 2.89), with no significant differences between the intervention groups.

The macula, as the central part of the retina, plays an important role in the reading process. However, its morphology has not been previously studied in the context of dyslexia. In this research, we compared the thickness of the fovea, parafovea and perifovea between dyslexic subjects and normal controls, in 11 retinal segmentations obtained by optical coherence tomography (OCT). With this aim, we considered the nine sectors of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid and also summarized data from sectors into inner ring subfield (parafovea) and outer ring subfield (perifovea). The thickness in all the four parafoveal sectors was significantly thicker in the complete retina, inner retina and middle retina of both eyes in the dyslexic group, as well as other macular sectors (fovea and perifovea) in the inner nuclear layer (INL), inner plexiform layer (IPL), IPL + INL and outer plexiform layer + outer nuclear layer (OPL + ONL). Additionally, the inner ring subfield (parafovea), but not the outer ring subfield (perifovea), was thicker in the complete retina, inner retina, middle retina (INL + OPL + ONL), OPL + ONL, IPL + INL and INL in the dyslexic group for both eyes. In contrast, no differences were found between the groups in any of the sectors or subfields of the outer retina, retinal nerve fiber layer, ganglion cell layer or ganglion cell complex in any eye. Thus, we conclude from this exploratory research that the macular morphology differs between dyslexic and normal control subjects, as measured by OCT, especially in the parafovea at middle retinal segmentations.

Background: We aim to assess whether time of day modified the treatment effect in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion Trial), a cluster-randomized trial that did not demonstrate the benefit of direct transportation to a thrombectomy-capable center versus nearest local stroke center for patients with a suspected large vessel stroke triaged in nonurban Catalonia between March 2017 and June 2020., Methods: We performed a post hoc analysis of RACECAT to evaluate if the association between initial transport routing and functional outcome differed according to trial enrollment time: daytime (8:00 am-8:59 pm) and nighttime (9:00 pm-7:59 am). Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with ischemic stroke. Subgroup analyses according to stroke subtype were evaluated., Results: We included 949 patients with an ischemic stroke, of whom 258 patients(27%) were enrolled during nighttime. Among patients enrolled during nighttime, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days (adjusted common odds ratio [acOR], 1.620 [95% CI, 1.020-2.551]); no significant difference between trial groups was present during daytime (acOR, 0.890 [95% CI, 0.680-1.163]; P interaction =0.014). Influence of nighttime on the treatment effect was only evident in patients with large vessel occlusion(daytime, acOR 0.766 [95% CI, 0.548-1.072]; nighttime, acOR, 1.785 [95% CI, 1.024-3.112] ; P interaction <0.01); no heterogeneity was observed for other stroke subtypes ( P interaction >0.1 for all comparisons). We observed longer delays in alteplase administration, interhospital transfers, and mechanical thrombectomy initiation during nighttime in patients allocated to local stroke centers., Conclusions: Among patients evaluated during nighttime for a suspected acute severe stroke in non-urban areas of Catalonia, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days. This association was only evident in patients with confirmed large vessel occlusion on vascular imaging. Time delays in alteplase administration and interhospital transfers might mediate the observed differences in clinical outcome., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02795962.

Background: Acute ischemic stroke patients not referred directly to a comprehensive stroke center (CSC) have reduced access to endovascular treatment (EVT). The RACECAT trial is a population-based cluster-randomized trial, designed to compare mothership and drip-and-ship strategies in acute ischemic stroke patients outside the catchment area of a CSC., Aims: To analyze the evolution of performance indicators in the regions that participated in RACECAT., Methods: This retrospective longitudinal observational study included all stroke alerts evaluated by emergency medical services in Catalonia between February 2016 and February 2020. Cases were classified geographically according to the nearest SC: local SC (Local-SC) and CSC catchment areas. We analyzed the evolution of EVT rates and relevant workflow times in Local-SC versus CSC catchment areas over three study periods: P1 (February 2016 to April 2017: before RACECAT initiation), P2 (May 2017 to September 2018), and P3 (October 2018 to February 2020)., Results: We included 20603 stroke alerts, 10,694 (51.9%) of which were activated within Local-SC catchment areas. The proportion of patients receiving EVT within Local-SC catchment areas increased (P1 vs. P3: 7.5% (95% confidence interval (CI), 6.4-8.7) to 22.5% (95% CI, 20.8-24.4) p  < 0.001). Inequalities in the odds of receiving EVT were reduced for patients from CSC versus Local-SC catchment areas (P1: odds ratio (OR) 3.9 (95% CI, 3.2-5) vs. P3: OR 1.5 (95% CI, 1.3-1.7) In Local-SC, door-to-image (P1: 24 (interquartile range (IQR) 15-36), P2: 24 (15-35), P3: 21 (13-32) min, p  < 0.001) and door-to-needle times (P1: 42 (31-60), P2: 41 (29-58), P3: 35 (25-50) p  < 0.001) reduced. Time from Local-SC arrival to groin puncture also decreased over time (P1: 188 [151-229], P2: 190 (157-233), P3: 168 (127-215) min, p  < 0.001)., Conclusion: An increase in EVT rates in Local-SC regions with a significant decrease in workflow times occurred during the period of the RACECAT trial.

Low energy availability may precede or be caused by cognitive disturbances in professional athletes. Related psychological problems include disordered eating patterns, body shape preoccupation, depression or anxiety. The objective of this research was to evaluate the effects of different personalised dietary plans on psychological factors in young professional female handball players with low energy availability. This 12-week randomised clinical trial involved 21 female players aged 22 ± 4 years, 172.0 ± 5.4 cm and 68.4 ± 6.7 kg divided into three groups (FD: free diet; MD: Mediterranean diet; HAD: high antioxidant diet). Eating behaviour (Eating Attitude Test, EAT-26: diet, bulimia and oral control subscales), body image (Body Shape Questionnaire, BSQ) and mood state (Profile of Mode State, POMS: tension, vigour, anger, depression, fatigue) were assessed. All participants showed low energy availability (<30 kcal/lean mass per day). The different plans showed no significant differences between them but significant differences over time within groups for the variables: body image, Tension, Vigour and Depression ( p < 0.05). Eating behaviour improved slightly but did not show statistically significant changes. Following an adequate nutritional planning for athletes seems to improve the mood and body perception of young female handball players. A longer intervention period is required to assess the differences between diets and improvement of other parameters.

Energy deficits are often observed in athletes, especially in female athletes, due to the high expenditure of sport and strict diets. Low energy availability can cause serious health problems and affect sport performance. The aim of this study was to evaluate the effects of different personalized dietary plans on physiological and physical factors related to energy deficit syndrome in female professional handball players. Twenty-one professional female handball players, aged 22 ± 4 years, 172.0 ± 5.4 cm and 68.4 ± 6.7 kg, divided into three groups (FD: free diet; MD: Mediterranean diet; and AD: high antioxidant diet), participated in this 12-week randomized controlled trial. Energy expenditure through indirect calorimetry, energy availability, 7 day dietary intake analysis, blood pressure, cholesterol, menstrual function, body composition by both anthropometry and bioelectrical impedance, and strength performance were assessed. All participants showed low energy availability (<30 kcal/lean mass per day); despite this, all had eumenorrhea. Significant improvements were found after the intervention in all components of body composition ( p < 0.05). In the remaining variables, despite slight improvements, none were significant neither over time nor between the different groups. Low energy availability has been observed in all professional female handball players, which may lead to serious consequences. A longer period of intervention is required to assess the differences between diets and improvements in other parameters.

Women's elite sports have experienced an exponential increase in the last decade, as has beach handball (BH). The high demands of this sport mean that athletes need to be in superior physical condition, so nutrition and body composition are determining factors in their sporting performance. For this reason, the aim of this study was to analyze, compare and correlate the most relevant variables of food intake (quantitative), body composition (focus on the bone mass characteristics) and sprint performance in female professional BH players. Thirty-three women from the National Spanish Team participated in this study. Dietary assessment, anthropometric measurements and sprint tests were performed. In general, the players had a low carbohydrate intake and adequate protein intake, with no significant differences depending on the category and playing position. For senior players, positive correlations were found between protein intake and bone mass ( r = 0.584, p = 0.022), polyunsaturated fatty acid intake and muscle mass ( r = 0.387, p = 0.026) and finally between fat mass and animal protein intake ( r = 0.569, p = 0.027). Body composition was similar in both categories; however, goalkeepers had the highest fat (22.6 ± 3.86%, 16.2 ± 4.84 kg) component (vs. wings: 17.4 ± 3.53%, p = 0.031/vs. specialists: 11.1 ± 1.91 kg, p = 0.034), and senior players had higher muscle mass (kilograms). It is worth noting the finding that players with a greater trochanter height had significantly lower sprint times ( p = 0.014 and p = 0.048 for 5 and 10 m, respectively). Certain bone characteristics, such as iliospinale height, biacromial and bimalleolar diameters, mesosternal perimeter and biceps skinfold, differ depending on the position. In addition, the greater speed of the senior players may be due to the greater specialization, number of training sessions performed and specific bone characteristics, such as trochanter height. In this regard, the data provided in this study will assist with establishing criteria for the selection of talent for this sporting discipline.

Background: Gluten intolerance is a systemic process of autoimmune nature; it develops in genetically predisposed subjects with gluten ingestion. The only treatment for celiac disease (CD) is a lifelong strict gluten-free diet (GFD). This study was designed to evaluate adherence to a GFD, risk of an eating disorder, and nutritional status in adult CD patients undergoing different interventions., Methods: A total of 28 Spanish women, aged 40 years or more, took part in a randomized controlled trial. Each group received a different intervention: group 1, gluten-free nutrition plan + exercise (GFD + E); group 2, gluten-free nutrition plan (GFD); group 3, celiac controls (NO-GFD); and group 4, non-celiac controls (CONTROL). The training was prescribed by a sport scientist. It was based on resistance training with elastic bands; beforehand a warm-up was performed and the resistance was increased progressively. The variables studied were adherence to the GFD, risk of eating disorders, blood values, and body composition., Results: Celiac women with personalized nutritional planning presented greater adherence to a gluten-free diet ( p < 0.001). Regarding leukocytes, significant differences were observed between the GFD and control groups ( p = 0.004). Perimeters and folds did not decrease significantly., Conclusion: Women with celiac disease who follow an adapted and personalized diet have a better adherence to a GFD compared to those who follow a non-professional diet, and therefore have a better immune system status (blood leukocytes)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Martínez-Rodríguez, Loaiza-Martínez, Sánchez-Sánchez, Rubio-Arias, Alacid, Prats-Moya, Martínez-Olcina, Yáñez-Sepúlveda, Asencio-Mas and Marcos-Pardo.)

The period of Ramadan induces changes in the usual eating patterns of individuals. During this period, Muslims must abstain from drinking and eating from dawn to dusk. Therefore, some research conducted on professional soccer players has observed that during and/or after Ramadan, performance, running speed, agility, dribbling speed, and endurance and/or skill performance in athletic events may be negatively affected by Ramadan intermittent fasting (RIF). The objective of this study was to analyze the influence of a dietary plan during RIF on performance and body composition in a professional soccer player. A 20-year-old elite player (86.0 kg, 188.5 cm) followed a dietary-nutritional plan with an isocaloric diet and was supplemented with glycerol. The athlete's strength and power in the lower limbs was assessed by performing a countermovement jump (CMJ) and Abalakov vertical jump (ABK) before and after Ramadan. After nutritional planning, the patient's body composition improved in terms of fat loss (6.61 to 5.70%) and muscle mass gain (50.26 to 51.50%). In addition, this translated into improvements in performance tests, both in the CMJ (36.72 to 40.00 cm) and ABK (39.16 to 49.34 cm). In conclusion, during a period of fasting, personalised nutritional planning and an appropriate supplementation and rest protocol can improve the body composition and performance of soccer players.

Triathlons are endurance events that include swimming, running, and cycling. Triathletes need to eat optimally during training and competitions to maximize their potential for success. The presence of carbohydrates in the mouth could activate regions in the brain to enhance athletic performance in exercise., Methods: This study examined the effects of glucose and mouthwash in ten male triathletes (age: 26.0 ± 8.7 years, height: 173.6 ± 10.4 cm, BMI 22.0 ± 1.7 kg/m 2 ). The four oral test solutions included (A) Rinse with placebo, (B) Water + gel with placebo, (C) Rinse with 15% CH concentration, and (D) Water + gel with 15% CH concentration (25 g gel in 165 mL water). The Rate of Perceived Exertion (RPE), Sensation Scale (FS), Felt Arousal Scale (FAS), Profile of Mood States (POMS), blood glucose, sprints, and dietary habits were assessed in each subject. All preceded ingestion of the oral-based test solution during workouts., Results: RPE showed no significant differences for subjective perceptions. The same was observed for FS and sprints. FAS scores increased over time ( p = 0.039) in all groups. POMS score increased significantly in group D ( p = 0.041). There was no effect of time on plasma glucose levels ( p = 0.737). As for correlations, positive correlations were observed between sprint and FAS variables ( p = 0.011)., Conclusions: It appears that CH intake correlates positively with mood, but in all other variables, there are no differences depending on the product.

Entomopathogenic fungi are gaining acceptance in Integrated Pest Management (IPM) systems as effective and environmental safety biological control agents to protect a great variety of crops against pest insects. Many of these insect-pathogenic fungi can establish themselves as endophytes and thereby may induce the plant immune system. The activation of plant defenses by the fungal endophytic colonization can have a direct impact on herbivores and plant pathogens. An integral component of many plant defense responses is also the release of volatile organic compounds, which may serve as an indirect defense by attracting the natural enemies of herbivores. Here we investigated the effect of endophytic colonization by the entomopathogenic fungus Beauveria bassiana on the volatile emission by melon and cotton plants, either unharmed or after being damaged by sap-sucking aphids or leaf chewing caterpillars. We found that when the plants are colonized by B. bassiana they emit a different blend of volatile compounds compared to uncolonized control plants. Some of the emitted compounds have been reported previously to be released in response to herbivory and have been implicated in natural enemy attraction. Several of the compounds are also known to have antimicrobial properties. Therefore, endophytic colonization by B. bassiana might help to not only direct control insect pests but also increase the resistance of plants against agronomically important pests and phytopathogens., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 González-Mas, Gutiérrez-Sánchez, Sánchez-Ortiz, Grandi, Turlings, Manuel Muñoz-Redondo, Moreno-Rojas and Quesada-Moraga.)

Entomopathogenic fungi are sprayed commercially for aphid control in greenhouses. Recently, their ability to grow endophytically within plants was discovered, offering the opportunity for systemic biological control. Endophytic colonization of host plants could also influence life-table parameters and behavior of herbivores. We investigated lethal and pre-mortality effects of Beauveria bassiana and Metarhizium brunneum on Aphis gossypii ; aphids either received inoculum while feeding on recently sprayed leaves (surface inoculum and endophytically-colonized) or while feeding on unsprayed but endophytically-colonized leaves. We used choice assays to identify any preferences for endophytically-colonized or control plants. Volatile emissions from endophytically-colonized plants and control plants were also compared. Aphid mortality rates ranged between 48.2 and 56.9 % on sprayed leaves, and between 37.7 and 50.0 on endophytically-colonized leaves. There was a significant effect of endophytic colonization on the rate of nymph production, but this did not result in an overall increase in the aphid population. Endophytic colonization did not influence host-plant selection even though there were qualitative and quantitative differences in the blend of volatiles released by endophytically-colonized and control plants. Although endophytic colonization did not change herbivore behavior, plants still benefit via indirect defense, resistance to plant pathogens or abiotic stress tolerance., Competing Interests: The authors declare no conflict of interest.

The red palm weevil (RPW) Rhynchophorus ferrugineus (Olivier) (Coleoptera: Curculionidae) is threatening the palm family worldwide, causing important economic losses. Current tactics to manage the weevil are largely based on chemical control, although the use of pesticides is hampered by several environmental constraints. Since the first introduction of RPW in Spain in 1996 and during its progressive spread around the Mediterranean basin, the number of reports of natural infection of RPW populations by entomopathogenic fungi (EPF) has been rising for 15 years, and this rise could support a pest-mediated EPF spread. To challenge this hypothesis, we assessed the usefulness of the region of elongation factor 1-alpha (EF1-α), Bloc nuclear intergenic region (Bloc) and inter simple sequence repeat (ISSR) markers, alone or in combination, to infer the relationships among Mediterranean Beauveria and Metarhizium strains isolated from the RPW. Second, the effect of abiotic factors, such as temperature, humidity and UV-B radiation, on the germination and growth of these EPFs strains as a function of their genealogy and geographic origin were determined. Finally, the pathogenicity of strains from different genetic clades was evaluated against larvae and adults of R. ferrugineus. The phylogenetic analysis based on the EF-1α gene identified eight different sequences among 24 fungal isolates of four fungal species. Similar clades were clustered when Bloc and ISSR analyses were performed. The results showed that strains of different origins were clustered in the same clade, and this outcome could be explained by an RPW-mediated EPF spread that was also influenced by time, geographical and other RPW related factors. Neither the response to abiotic factors nor virulence to RPW larvae and adults were related to the sequence type, with all B. bassiana strains well adapted to Mediterraneam climatic conditions. Taken together, these findings may help to select the best strain for RPW management., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to investigate whether early-onset schizophrenia (EOS) cases differ from controls regarding volumes of the total cerebellum and the right and left cerebellar hemispheres, and volumetric asymmetry. Correlations of cerebellar volumes and asymmetry indices with severity of symptoms and general functioning in cases of EOS were also assessed., Methods: Adolescents with EOS (n = 23) were compared with controls (n = 23). Sociodemographic and clinical data, and magnetic resonance imaging scans that were acquired for routine clinical purposes were collected retrospectively. Cerebellar volumes were evaluated using the stereological method. Asymmetry indices were subsequently calculated. Scores of the Positive and Negative Syndrome Scale and the Children's Global Assessment Scale were used to assess the severity of symptoms and general functionality., Results: There were no significant differences in any of the cerebellar volumes and asymmetry indices between the two groups. Neither cerebellar volumes nor asymmetry indices were correlated with the severity of symptoms and general functionality in EOS., Conclusions: Our findings suggest that the early-onset form of schizophrenia does not show apparent volumetric changes of the cerebellum. Additionally, the neural circuits involved in formation of symptomatology may not reflect any correlation with cerebellar volumes at mid-adolescence.

Objective: To compare whether there are any differences between the 3 methods used for measure area of foramen magnum (FM) in skulls., Methods: The FMs of 150 skulls were examined. Antero-posterior diameter, transverse diameter were measured using by Vernier caliper. The area of the FM was calculated by using 2 different formulas as described previously by Radinsky and Teixeira.The authors also applied stereological assessment method for estimating the surface area of FMs. The area was calculated 3 times manually using stereological point grid system for each skull.The authors compared the mean surface area of FMs obtained from each of these 3 methods estimating surface area of FMs whether there were any significant differences in between their results., Results: The mean areas of the FMs estimated according to Teixeria formula, Radinsky formula, and Cavalieri stereological method were respectively as follows: 790.47 ± 99.86 mm, 783.66 ± 99.34 mm, and 748.06 ± 100.19 mm. The authors observed significant differences (P < 0.05) in between the mean surface areas of FMs obtained from each of these 3 methods used for estimating the area., Conclusion: There were significant differences (P < 0.05) in between the mean surface areas of FMs obtained from each of these 3 methods used for estimating the area.

The orbit is very frequently damaged by traumas which result in not only bone deficits, but also functional deformities if reconstruction is not appropriate. Anatomical exposure of the bony orbit is of importance for both anatomists and surgeons who perform operation on this area. The current study evaluated the group of morphometrical parameters on 74 adult West Anatolian dry skulls and stereological surface area on the dry skull orbits while describing the clinical importance. Surface areas on the orbital base of the skulls were also evaluated using stereological method, bilaterally. Anthropological assessment of orbital base (in terms of width and height) revealed no significant difference between right and left sides. Both width and height of the optic foramen were significantly higher on the right side compared to left. The distances between the margins (medial, lateral, superior, inferior) of the orbital base and the optic foramen were longer on the right side compared to left, except the distances between the lateral margins. There was no significant difference among the subjects between right and left sides with respect to the orbital base in terms of stereological area calculation. The results are significant because there are no recorded anatomical data on West Anatolian skulls at previous researches. (Folia Morphol 2018; 77, 1: 105-109).

Background: Tinnitus is the recognition of sound in the absence of any external auditory stimulus to the noise of ringing in the ears. Middle ear aeration carries important role for ossicular coupling and normal hearing. There is restricted morphometric data on the cases with bilateral tinnitus., Materials and Methods: In this study we evaluated hearing findings of 18 cases with subjective nonpulsatile bilateral tinnitus and also morphometry and volumetry of temporal bone substructures on the computed tomography images using stereological method compared with the gender and age matched 12 healthy subjects. Duration of tinnitus, exposing acoustic trauma or/and high level noise levels, evaluation of middle ear volume, jugular bulb levels, distances between jugular bulb and both oval window and middle ear were evaluated., Results: Both males and females with tinnitus showed worse hearing thresholds through bone and air conductions than healthy subjects but it was not statistically significant. Pure tone thresholds through bone and air conductions were not statistically different in both sexes with bilateral tinnitus. Right middle ear volume of the cases with bilateral tinnitus was mean 5.57 cm3 for males and 5.64 cm3 for females; and also the left middle ear volume of the cases with bilateral tinnitus was mean 5.87 cm3 for males and 5.65 cm3 for females. There were no significant differences between the cases with bilateral tinnitus and the control subjects according to the side of the body., Conclusions: The data on the hearing findings and morphometrical evaluation of the cases with bilateral tinnitus may be important for anatomists and clinicians. (Folia Morphol 2018; 77, 1: 57-64).

Two-component systems (TCS) regulate diverse processes such as virulence, stress responses, metabolism and antibiotic resistance in bacteria but are absent in humans, making them promising targets for novel antibacterials. By incorporating recently described TCS histidine kinase autophosphorylation inhibitors (HKAIs) into ε-poly-L-lysine capped nanoparticles (NPs) we could overcome the Gram negative (Gr-) permeability barrier for the HKAIs. The observed bactericidal activity against Gr- bacteria was shown to be due to the enhanced delivery and internalization of the HKAIs and not an inhibitory or synergistic effect of the NPs. The NPs had no adverse effects on mammalian cell viability or the immune function of macrophages in vitro and showed no signs of toxicity to zebrafish larvae in vivo. These results show that HKAIs are promising antibacterials for both Gr- and Gr+pathogens and that NPs are a safe drug delivery technology that can enhance the selectivity and efficacy of HKAIs against bacteria., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A disulfide-bridged peptide drug development candidate contained two oligopeptide chains with 11 and 12 natural amino acids joined by a disulfide bond at the N-terminal end. An efficient biotechnology based process for the production of the disulfide-bridged peptide was developed. Initially, the two individual oligopeptide chains were prepared separately by designing different fusion proteins and expressing them in recombinant E. coli. Enzymatic or chemical cleavage of the two fusion proteins provided the two individual oligopeptide chains which could be conjugated via disulfide bond by conventional chemical reaction to the disulfide-bridged peptide. A novel heterodimeric system to bring the two oligopeptide chains closer and induce disulfide bond formation was designed by taking advantage of the self-assembly of a leucine zipper system. The heterodimeric approach involved designing fusion proteins with the acidic and basic components of the leucine zipper, additional amino acids to optimize interaction between the individual chains, specific cleavage sites, specific tag to ensure separation, and two individual oligopeptide chains. Computer modeling was used to identify the nature and number of amino acid residue to be inserted between the leucine zipper and oligopeptides for optimum interaction. Cloning and expression in rec E. coli, fermentation, followed by cell disruption resulted in the formation of heterodimeric protein with the interchain disulfide bond. Separation of the desired heterodimeric protein, followed by specific cleavage at methionine by cyanogen bromide provided the disulfide-bridged peptide.

Objective: To describe the case-mix of patients admitted to intensive care units (ICUs) in Spain during the period 2006-2011 and to assess changes in ICU mortality according to severity level., Design: Secondary analysis of data obtained from the ENVN-HELICS registry. Observational prospective study., Setting: Spanish ICU., Patients: Patients admitted for over 24h., Interventions: None., Variables: Data for each of the participating hospitals and ICUs were recorded, as well as data that allowed to knowing the case-mix and the individual outcome of each patient. The study period was divided into two intervals, from 2006 to 2008 (period 1) and from 2009 to 2011 (period 2). Multilevel and multivariate models were used for the analysis of mortality and were performed in each stratum of severity level., Results: The study population included 142,859 patients admitted to 188 adult ICUs. There was an increase in the mean age of the patients and in the percentage of patients >79 years (11.2% vs. 12.7%, P<0.001). Also, the mean APACHE II score increased from 14.35±8.29 to 14.72±8.43 (P<0.001). The crude overall intra-UCI mortality remained unchanged (11.4%) but adjusted mortality rate in patients with APACHE II score between 11 and 25 decreased modestly in recent years (12.3% vs. 11.6%, odds ratio=0.931, 95% CI 0.883-0.982; P=0.008)., Conclusion: This study provides observational longitudinal data on case-mix of patients admitted to Spanish ICUs. A slight reduction in ICU mortality rate was observed among patients with intermediate severity level., (Copyright © 2015 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.)

Air-liquid interface rings were observed on the side walls of stainless steel buffer vessels after certain downstream buffer preparations. Those rings were resistant to regular cleaning-in-place procedures but could be removed by manual means. To investigate the root cause of this issue, multiple analytical techniques, including liquid chromatography with tandem mass spectrometry detection (LC-MS/MS), high-resolution accurate mass liquid chromatography with mass spectrometry, nuclear magnetic resonance, Fourier transform infrared spectroscopy, and scanning electron microscopy with energy-dispersive X-ray spectroscopy have been employed to characterize the chemical composition of air-liquid interface rings. The main component of air-liquid interface rings was determined to be slip agents, and the origin of the slip agents can be traced back to their presence on raw material packaging liners. Slip agents are commonly used in plastic industry as additives to reduce the coefficient of friction during the manufacturing process of thin films. To mitigate this air-liquid interface ring issue, an alternate liner with low slip agent was identified and implemented with minimal additional cost. We have also proactively tested the packaging liners of other raw materials currently used in our downstream buffer preparation to ensure slip agent levels are appropriate., Lay Abstract: Air-liquid interface rings were observed on the side walls of stainless steel buffer vessels after certain downstream buffer preparations. To investigate the root cause of this issue, multiple analytical techniques have been employed to characterize the chemical composition of air-liquid interface rings. The main components of air-liquid interface rings were determined to be slip agents, which are common additives used in the manufacturing process of thin films. The origin of the slip agents can be traced back to their presence on certain raw material packaging liners. To mitigate this air-liquid interface ring issue, an alternate liner with low slip agent was identified and implemented., (© PDA, Inc. 2016.)

Objective: The aim of the study is to investigate coexistence of Wormian bones with metopism, and vice versa, in adult skulls., Materials and Methods: A total of 160 dry adult human skulls of unknown sex and ages were randomly selected from the Gross Anatomy Laboratory of Medical School of Dokuz Eylul University. The skulls were examined for presence of metopism, Wormian bones (WB), and coexistence of WBs with metopism and vice versa. Topographic distribution of the WBs was macroscopically evaluated within the skulls including metopism. The photographs were being taken with Canon 400B (55 mm objective)., Results: The frequency of metopism and WBs in 160 skulls is 7.50% (12/160) and 59.3% (95/160), respectively, P < 0.05 (). The incidence of coexistence of WBs with metopism was found as 11 of 12 skulls (91.66%), whereas the incidence of coexistence of metopism with WBs was found as 11 of 95 skulls (11.58%), P < 0.05 (). There were totally 23 sutures including WBs in 11 skulls, which had metopism (). The number (%) of metopic skulls for each specific suture including WBs were found as: 11 lamdoid sutures in 7/11 (63.63%) skulls, 4 lambda in 4/11 (36.36%) skulls, 2 asterion in 2/11 (18.18%) skulls, 1 squamous in 1/11 (9.09%) skull, 2 sagittal in 2/11 (18.18%) skulls, and 3 parieromsatoid sutures in 2/11 (18.18%) skulls (). The distribution of these 23 WBs in sutures of 11 skulls including metopisms is determined as follows: 11/23 (47.82%) WBs at lambdoid sutures [5/23 (21.74%) at the right lambdoid sutures and 6/23 (26.08%) at the left lambdoid sutures, and 4 pair of 11 WBs bilaterally located]; 4 (17.39%) WBs at lambda; 2/23 (8.69%) WBs at asterion [1/23 (4.34%) at the right asterion and 1/23 (4.34%) at the left asterion of 2 diverse skulls]; 2/23 (8.69%) WBs at sagittal sutures; 1/23 (4.34%) WBs at the left squamous suture; 3/23 (13.04%) WBs at parietomastoid sutures [2/23 (8.69%) at the right parietomastoid sutures and 1/23 (4.34%) at the left parietomastoid suture and 1 pair of them bilaterally located; , ].(Figure is included in full-text article.)(Table is included in full-text article.)(Table is included in full-text article.), Conclusions: : There was a significant difference in rates between coexistence of WBs with metopism (11/12, 91.66%) and coexistence of metopism with WBs (11/95, 11.58%). The factors leading to metopism may also lead to WBs, whereas that the factors leading to WBs may not lead to metopism.

Background: Medial fasciocutaneous flaps, which are based on the femoral artery from the thigh region, are used for wide inguinal, scrotal, vaginal, perineal, leg, head and neck defect reconstructions in injured human patients. Within this regard, anatomical knowledge about perforating and cutaneous branches of the femoral artery is important for the surgeons., Materials and Methods: In the present study, vascular pedicles of the medial thigh perforator flap based on the femoral artery were investigated according to anatomical and surgical landmarks. Human Caucasian preserved cadavers of 15 adults (13 males, 2 females; age range 55-82 years: 30 sides, bilaterally) that were previously formalin fixed were subjected to our analytical examinations. Micro dissections were performed under 4× loop magnification while representing the perforating branches of the femoral artery after filling by coloured latex injection via the external iliac artery., Results: The size and length parameters of these branches which appeared around the apex of the femoral triangle were evaluated. The mean size of the perforating branch at the point of origin was 0.14 cm and the mean size of the cutaneous branch at the point of origin was 0.09 cm, the mean length of the pedicle was 4.74 cm and the mean length of the cutaneous branch was 3.30 cm, respectively. Location of the perforating and the cutaneous branches were also determined according to the surgical landmarks such as the anterior superior iliac spine, inguinal ligament, pubic tubercle and interepicondylar line., Conclusions: The pedicle of the medial flap should locate up to 25 cm from the anterior superior iliac spine so as to preserve the vascular structures. Exact location of this artery helps the surgeons to perform anastomosis in an easier and safer manner during surgical operations.

Background: The aim of this study was to investigate the incidence of the suprascapular foramen in West Anatolian population., Materials and Methods: Eighty-one dried human scapulae of West Anatolian people of unknown ages and gender belonging to the Anatomy Department Laboratory of Dokuz Eylul University Medical School were examined macroscopically. The vertical and transverse diameters of the suprascapular foramen and central thickness of the ossified ligaments were measured with calliper in millimetres and digital calliper, respectively., Results: We observed the suprascapular foramen due to ossification of the suprascapular ligament only in 2 of 81 (2.47%) scapulae. The vertical and transverse diameters of the suprascapular foramen and central thickness of the ossified ligaments (No. 1 and No. 2) were measured as 8.0 mm vs. 4.0 mm, 3.6 mm vs. 2.0 mm and 4.0 mm vs. 1.4 mm, respectively., Conclusions: The suprascapular foramen caused by ossified suprascapular ligament is rarely observed variation in West Anatolian population.

Anteromedial thigh (AMT) flaps based on lateral circumflex femoral artery (LCFA) have characteristics which make them favourable for use in reconstruction of extensive thigh, head, neck and leg defects. AMT flap which is elevated on the artery has the advantages of low donor site morbidity and preservation of main arteries. Due to inconstant anatomy of the pedicle, the flap is mostly not preferable. Hence, we aimed to describe the anatomical features of the unnamed branch of the descending branch of the LCFA harvesting AMT flap. For this purpose, the external iliac artery was displayed bilaterally on 15 adult (13 males and 2 females; age range 55-82 years) preserved cadavers using latex injection. The perforator branch of the descending branch from the LCFA was microdissected under 4× loupe magnification. The perforator branch was located 28.53 (20.20-34.20) cm distal to the anterior superior iliac spine, 22.12 (13.40-28.00) cm distal to the pubic tubercle, and 13.20 (10.80-16.20) cm proximal to the interepicondylar line. At the level of origin point the mean diameter of the perforating branch was 0.17 cm and the mean diameter of its cutaneous branch was 0.14 cm. The mean length of the pedicle was 5.71 (3.70-9.00) cm. We conclude that our findings contribute to the literature in terms of anatomical knowledge for surgical safety.

Objective: The Wormian Bones are accessory bones located within the cranial sutures and fontanelles. The present article examines the incidence of Wormian Bones and compares the number and topographic distribution between the sutures including Wormian Bones in skulls of West Anatolian Population., Methods: One hundred fifty crania were examined. The parameters evaluated in the present study were as follows: the rate of skulls including Wormian Bones; the topographic distribution and frequencies of the sutures including Wormian Bones; the number of these sutures for each skull; the name and number of sutures that were bilaterally and symmetrically located on the right and left side of skull (paired sutures) and which coincidentally had Wormian Bones for each skull; the differences of frequencies between the paired sutures including Wormian Bones., Results: The rate of skulls including Wormian Bones was determined as 59.3%. The maximum and minimum numbers of sutures, including Wormian Bones, were 6 in 1 skull and 1 in each of 30 skulls, respectively. The maximum and minimum rates of sutures that had Wormian Bones were found in left lambdoid 40.7% and right occipitomastoid 1.3% sutures, respectively. There was only a significant difference between the rate of right and left squamous sutures (P = 0.04). Forty-five skulls were including 55 pairs of bilaterally and symmetrically located sutures that coincidentally had Wormian Bones in each pair. Each of 35 skulls had 1 pair of sutures including Wormian Bones and each of 10 skulls had 2 pairs., Conclusions: In the present study, the rate of Wormian Bones was determined as 59.3% in West Anatolian Population. This incidence rate is considerably lower than the other reports, and it may be as a result of racial variations. These divergent bones were more frequently found in left lambdoid sutures (40.7%) and less frequently in right occipitomastoid sutures (1.3%). This study may guide the investigators dealing with the neurosurgery, orthopedy, radiology, anatomy, and anthropology in their practice.

Objective: To describe the characteristics of the patients case-mix admitted to ICUs due to medical and surgical disease, and to compare both groups., Design: Analysis of data covering the period 2006-2011 in the ENVIN-HELICS registry. An observational, prospective, multicenter and voluntary participation study., Setting: A total of 188 Spanish ICUs., Patients: All patients admitted for more than 24 hours., Main Variables: Demographic data, cause of admission, severity scores, length of stay, mortality., Results: A total of 138,999 patients were analyzed. Of these, 65,467 (47.1%) were admitted due to a non-coronary medical cause, 27,785 (20,0%) due to coronary-related illness, 28,044 (20,2%) after elective surgery and 17,613 (12.7%) after urgent surgery. Use of devices, nosocomial infections and isolation of multirresistant organisms were more prevalent in urgent surgery patients. Longer length of stay (median 5 days; interquartile range 2-11) as well as higher severity scale values (APACHE II and SAPS II) corresponded to this same group of patients. Mortality was higher in non-coronay medical patients. On categorizing the patients according to the APACHE II score, mortality was seen to be higher in urgent surgery cases than in elective surgery patients in all groups. The largest difference was observed in the APACHE II score 6-10 group (3% vs. 0.9%) (OR: 2.14, 95% CI 1.825-2.513; p<0.001)., Conclusions: The mortality rate is higher in non-coronary medical patients, though resource use per patient is greater in the urgent surgery cases. The APACHE II scale underestimates mortality in emergency surgery patients., (Copyright © 2013 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.)

Anatomic variability and anastomosis of the angular artery of the facial artery with the other arteries are important for both anatomists and surgeons. In particular, the angular artery is a significant landmark in dacryocystorhinostomy. Because of variations on anatomy of the angular artery, there are limited numbers of anatomic studies on the flaps of facial region. Hence, the aim of the cadaveric study was to evaluate the anatomic features of the angular artery in detail to help surgical procedures.The artery was represented under ×4 loop magnification in 32 sides of 16 formalin-fixed adult cadavers. The angular artery's position, diameter, and branch patterns relevant to the nose arterial supply were evaluated. The facial artery ended symmetrically in 10 (62.5%) of the cadavers. The facial artery was terminated as angular artery in all of the cases. The types of the angular artery were as follows: classical angular type in 8 cases (25.0%), nasal type in 15 cases (46.9%), alar type in 4 cases (12.5%), and labial type in 5 cases (15.6%) on the facial halves. We studied the topographic anatomic features of the angular artery for increasing reliability of the flaps on the region. The angular arterial anatomic details are critical and essential for surgical cosmetic and functional results.

We have determined the magnetic structure of the intermetallic compound Gd2Fe2Si2C using neutron powder diffraction, (155)Gd and (57)Fe Mössbauer spectroscopy. This compound crystallizes in a monoclinic (C2/m) structure and its magnetic structure is characterized by antiferromagnetic order of the Gd sublattice along the b-axis, with cell-doubling along the c-axis. The propagation vector is k = [0 0 ½]. At 3.6 K the Gd moment reaches 6.2(2) μ(B). Finally, (57)Fe Mössbauer spectroscopy shows no evidence of magnetic ordering of the Fe sublattice.

Objectives: This study was designed to evaluate effects of hyperbaric oxygen (HBO) plus 3-aminobenzamide (3-AB) cotreatment on tissue oxidative stress parameters (TOSp), tissue histopathology scores (THSc), and bacterial translocations (Bact-Trans) in an experimental model of severe acute pancreatitis (AP)., Methods: Seventy-five Sprague-Dawley rats were randomized into 5 groups. Group 1 received sham. Severe AP was induced by intraductal taurocholate infusion and then group 2 received saline, group 3 received 3-AB, group 4 received 3-AB plus HBO, and group 5 received HBO. 3-Aminobenzamide (10 mg/kg per day, once daily, intraperitoneal) and saline (1 mL/kg) were started right after the induction, whereas HBO (2,8 atm pressure, BID, 90 minutes each) was started at the sixth hour. The rats were euthanized at the 54th hour, and TOSp, THSc, and Bact-Trans were studied., Results: In treatment groups 3 and 5, Bact-Trans (P < 0.05, P < 0.05), TOSp (P < 0.05, P < 0.05), and THSc (P < 0.001, P < 0.001) were significantly lower than controls. In addition to these findings, group 4 (cotreatment) showed the most significant effect on Bact-Trans and THSc (P < 0.001, P < 0.001) and also better in TOSp (P < 0.02)., Conclusions: Poly(ADP-ribose) polymerase inhibition by 3-AB and HBO treatment alone was effective in the course of severe AP, and favorable with cotreatment because of the improved cascades of inflammatory process by different aspects.

Nonmotor symptoms (NMS) in Parkinson's disease (PD) can precede onset of motor symptoms. Relationship between premotor symptoms onset and motor features is limited. Our aim is to describe the presence and perceived onset of NMS in PD as well as their possible association with motor phenotype. Presence and onset of NMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls from 11 Spanish and Austrian centers. Seventeen of thirty-one NMS were more common in patients than controls (P < 0.05). They were usually mild and frequently reported to occur at different time-spans before motor symptoms. Anhedonia, apathy, memory complaints, and inattention occurred more frequently during the 2-year premotor period. Those reported more frequently in the 2- to 10-year premotor period were smell loss, mood disturbances, taste loss, excessive sweating, fatigue, and pain. Constipation, dream-enacting behavior, excessive daytime sleepiness, and postprandial fullness were frequently perceived more than 10 years before motor symptoms. No correlation between NMS burden and motor severity, age, or gender was observed. NMS associated in four clusters: rapid eye movement sleep behavior disorder symptoms-constipation, cognition-related, mood-related, and sensory clusters. No cluster was associated with a specific motor phenotype or severity. NMS are common in early unmedicated PD and frequently reported to occur in the premotor period. They are generally mild, but a patient subgroup showed high NMS burden mainly resulting from cognition-related symptoms. Certain NMS when present at the time of assessment or in the premotor stage, either alone or in combination, allowed discriminating PD from controls., (© 2014 International Parkinson and Movement Disorder Society.)

Introduction: The International Headache Society (IHS) has published the third edition of the International Classification of Headache Disorders (ICHD-III beta), the most commonly used guide to diagnosing headaches in the world., Aims: To review the recent additions to the guide, to explain the new entities that appear in it and to compare the conditions that have had their criteria further clarified against the criteria in the previous edition., Development: We have recorded a large number of clarifications in the criteria in practically all the headaches and neuralgias in the classification, but the conditions that have undergone the most significant clarifications are chronic migraine, primary headache associated with sexual activity, short-lasting unilateral neuralgiform headache attacks, new daily persistent headache, medication-overuse headache, syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis. The most notable new entities that have been incorporated are external-compression headache, cold-stimulus headache, nummular headache, headache attributed to aeroplane travel and headache attributed to autonomic dysreflexia. Another point to be highlighted is the case of the new headaches (still not considered entities in their own right) included in the appendix, some of the most noteworthy being epicrania fugax, vestibular migraine and infantile colic., Conclusions: The IHS recommends no longer using the previous classification and changing over to the new classification (ICHD-III beta) in healthcare, teaching and research, in addition to making this new guide as widely known as possible.

The increasing financial pressures of health care insurance coverage have become a key issue for advanced economies. This study tests whether hospital financial pressures have an effect on the health of the uninsured population. To do so, the author investigates the implications of managed care for the uninsured in the United States. Managed care penetration has increased financial pressures on hospitals, and previous work has shown that safety net hospitals have been affected more severely. The study results reveal that charity care patients concentrate in government hospitals in areas where financial pressures imposed by managed care are greater. In addition, the quality of care of these hospitals decreases more in areas where managed care penetration is stronger. Finally, the stronger financial pressures that managed care diffusion imposes have a negative effect on the quality of care the uninsured and those admitted to government hospitals receive.

A new approach towards the design of "gated scaffolds" based on the combination of capped mesoporous silica nanoparticles (MSNs) with porous biomaterials is reported. Using this approach, a 3D gelatin-based scaffold able to selectively deliver cargo in the presence of an APase enzyme is prepared and tested. This new design opens up the possibility of developing new smart biomaterials with advanced drug-delivery features., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Cerebellum is responsible to higher cognitive functions and delicate motor activity. Because of its significance, cerebellum may play a major role in cognitive, behavioral, and psychiatric diseases. Therefore, the investigations on cerebellum may be contributed to the future researches so as to solve reasons of the diseases. The rabbit brain relatively larger than the rat and mouse brain and the individual evaluation of its subdivisions are rather easy. There are no data on cerebellar volume of rabbits in literature. Thus, the study presents microscopic volume calculation of rabbits' cerebellum using the stereological method. The mean (SD) calculated volume of the cerebellum in the rabbit brain was found to be 0.69 (0.03) cm3. The individual microscopic volume estimation of an animal subject can be achieved by Cavalier method. Researchers believed that the findings and the applied method in this study may be useful for the scientists.

The application of stereologic techniques to the analysis of the nervous system has greatly contributed to the evaluation of the normal and pathological anatomy of the aging brain. Currently, the hippocampus still holds secrets about the aging process. Experimental researches on hippocampus morphology may contribute to the future researches. This study presents the volume and weight of left hippocampus using a stereological technique on light microscope. The mean weight of the encephalon without cerebellum was 6.1 ± 0.1 g. The mean weight and the volume of the hippocampus were (mean ± SD) 0.28 ± 0.02 g and 0.28 ± 0.02 cm3, respectively. The mean coefficient of error for the stereological volume estimation of the hippocampus was 0.03. The individual volume estimation of the subjects may be achieved by the Cavalieri method. Investigators believed that the findings and the applied technique in this study may be useful for clinicians.

pH-sensitive gated mesoporous silica nanoparticles have been synthesized. Increased extracellular pH and internalization into living yeast cells triggered molecular gate aperture and cargo release. Proper performance of the system was demonstrated with nanodevices loaded with fluorescein or with the antifungal agent tebuconazole. Interestingly, nanodevices loaded with tebuconazole significantly enhanced tebuconazole cytotoxicity. As alterations of acidic external pH are a key parameter in the onset of fungal vaginitis, this nanodevice could improve the treatment for vaginal mycoses.

The synthesis and characterization of two new capped silica mesoporous nanoparticles for controlled delivery purposes are described. Capped hybrid systems consist of MCM-41 nanoparticles functionalized on the outer surface with polymer ε-poly-L-lysine by two different anchoring strategies. In both cases, nanoparticles were loaded with model dye molecule [Ru(bipy)3](2+). An anchoring strategy involved the random formation of urea bonds by the treatment of propyl isocyanate-functionalized MCM-41 nanoparticles with the lysine amino groups located on the ε-poly-L-lysine backbone (solid Ru-rLys-S1). The second strategy involved a specific attachment through the carboxyl terminus of the polypeptide with azidopropyl-functionalized MCM-41 nanoparticles (solid Ru-tLys-S1). Once synthesized, both nanoparticles showed a nearly zero cargo release in water due to the coverage of the nanoparticle surface by polymer ε-poly-L-lysine. In contrast, a remarkable payload delivery was observed in the presence of proteases due to the hydrolysis of the polymer's amide bonds. Once chemically characterized, studies of the viability and the lysosomal enzyme-controlled release of the dye in intracellular media were carried out. Finally, the possibility of using these materials as drug-delivery systems was tested by preparing the corresponding ε-poly-L-lysine capped mesoporous silica nanoparticles loaded with cytotoxic drug camptothecin (CPT), CPT-rLys-S1 and CPT-tLys-S1. Cellular uptake and cell-death induction were studied. The efficiency of both nanoparticles as new potential platforms for cancer treatment was demonstrated., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

About 15% of people in the world suffer migraine attacks. Migraine can induce a great impact in the quality of life, and the costs of medical care and loss of productivity can be also high. Non-steroidal anti-inflammatory drugs (NSAIDs) are the best treatment in mild-to-moderate migraine attacks and triptans are the first line option in the acute treatment of moderate-to-severe migraine attacks. At present, there are seven marketed triptans: sumatriptan, rizatriptan, zolmitriptan, eletriptan, naratriptan, almotriptan and frovatriptan. Obviously, every drug presents different pharmacokinetic and pharmacodynamics properties and, moreover, some triptans have several formulations. The prescription of one of these seven triptans for a specified patient is based in the drug profile: efficacy, safety, pharmacokinetics and pharmacodynamics. Other data to take account in the final prescription are clinical characteristics of the migraine attack (speed of onset, intensity of pain, lasting of the attack) and patient characteristics as working habits, life style or medical history. It is therefore mandatory to perform an individualization of the treatment of migraine attack. In recent years, several new patents of drugs have been registered in the treatment of migraine attack, although most of these are already known drugs that only provide new routes of administration. We present an update on the treatment of the migraine attack.

Chronic migraine is the most frequent and disabling complication of migraine. To date, only two drugs have been specifically analysed for the treatment of chronic migraine, topiramate and onabotulinumtoxin A, and in the evidence-based medicine categories, they have achieved level of evidence I and as such, a grade of recommendation A according to current guidelines. Following the PREEMPT paradigm, pericranial intramuscular onabotulinumtoxin A injections show a good efficacy and safety in chronic migraine patients, both in phase III randomized clinical trials and in a pooled data analyses. Onabotulinumtoxin A injections reduce the number of days of headache and migraine, they reduce the consumption of triptans and disability, and improve the quality of life of migraine patients. For these reasons, onabotulinumtoxin type A is an option as valid as topiramate for the treatment of chronic migraine.

Bug busters: A novel nanodevice consisting of mesoporous nanoparticles loaded with vancomycin and capped with ε-poly-L-lysine (ε-PL) was prepared and its interaction with different Gram-negative bacteria studied. A remarkable improvement in the efficacy of the antimicrobial drug ε-PL and a broadening of the antimicrobial spectrum of vancomycin is demonstrated., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Healthcare financing and insurance is changing everywhere. We want to understand the impact that financial pressures can have for the uninsured in advanced economies. To do so we focus on analyzing the effect of the introduction in the US of managed care and the big rise in financial pressures that it implied. Traditionally, in the US safety net hospitals have financed their provision of unfunded care through a complex system of cross-subsidies. Our hypothesis is that financial pressures undermine the ability of a hospital to cross-subsidize and challenges their survival. We focus on the impact of price pressures and cost-controlling mechanisms imposed by managed care. We find that financial pressures imposed by managed care disproportionately affect the closure of safety net hospitals. Moreover, amongst those hospitals that remain open, in areas where managed care penetration increases the most, they react by closing the health services most commonly used by the uninsured.

As part of the process-characterization campaign of a candidate vaccine product, a recently developed class of three-level designs-definitive-screening designs-was employed to select a quadratic model that describes the effect of six input process parameters, including protein concentration, formaldehyde-to-protein ratio, lysine concentration, reaction duration, pH, and reaction temperature, on a formylation protein-crosslinking reaction. This design requires only 17 experimental runs. The resulting model was then used to simulate 10,000 runs that account for the variability in the inputs expected on manufacturing scale. The extent of protein polymerization was predicted to be within specifications for all simulated runs, demonstrating the robustness of the unit operation for subsequent process validation and future commercial manufacturing.

The aim of this multicentric study was to compare the anatomical structures of temporal bone in patients with unilateral tinnitus with their healthy ears. We also aimed at evaluating whether age and gender-related asymmetrical changes occur in temporal bones or not. Fifty two ears of 26 patients who had unilateral tinnitus were included into the retrospective study. The patients who had subjective nonpulsatile tinnitus and who previously had temporal computed tomography according to their file records were accepted to study. Temporal CT scans and audiometric results of patients were examined retrospectively. Middle ear volume, diameter of internal acoustic meats and diameter of jugular bulb were evaluated by both anatomist and radiologist, interobserverly. Internal acoustic meats and jugular bulb were found larger in the ears that had tinnitus than healthy ears; however, there was no statistically significance. The stereological morphometrical study of temporal bone asymmetry in humans correlate with sex is of importance for both otolarygologs and anatomists. These results will contribute to data on middle ear volume, internal acustic meats and jugular bulb sizes.

The preparation of a new capped silica mesoporous material, Rh-Azo-S, for on-command delivery applications in the presence of target enzymes is described. The material consists of nanometric mesoporous MCM-41-like supports loaded with Rhodamine B and capped with an azopyridine derivative. The material was designed to show "zero delivery" and to display a cargo release in the presence of reductases and esterases, which are usually present in the colon, mainly due to intestinal microflora. The opening and cargo release of Rh-Azo-S in vitro studies were assessed and seen to occur in the presence of these enzymes, whereas no delivery was noted in the presence of pepsine. Moreover, Rh-Azo-S nanoparticles were used to study controlled Rhodamine B dye delivery in intracellular media. HeLa cells were employed for testing the "non"-toxicity of nanoparticles. Moreover, delivery of the dye in these cells, through internalization and enzyme-mediated gate opening, was confirmed by confocal microscopy. Furthermore, the nanoparticles capped with the Azo group and loaded with a cytotoxic camptothecin (CPT) were also prepared (solid CPT-Azo-S) and used as delivery nanodevices in HeLa cells. When this solid was employed, the cell viability decreased significantly due to internalization of the nanoparticles and delivery of the cytotoxic agent., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The synthesis and characterisation of new capped silica mesoporous nanoparticles for on-command delivery applications is reported. Functional capped hybrid systems consist of MCM-41 nanoparticles functionalised on the external surface with polyesters bearing azobenzene derivatives and rhodamine B inside the mesopores. Two solid materials, Rh-PAzo8-S and Rh-PAzo6-S, containing two closely related polymers, PAzo8 and PAzo6, in the pore outlets have been prepared. Materials Rh-PAzo8-S and Rh-PAzo6-S showed an almost zero release in water due to steric hindrance imposed by the presence of anchored bulky polyesters, whereas a large delivery of the cargo was observed in the presence of an esterase enzyme due to the progressive hydrolysis of polyester chains. Moreover, nanoparticles Rh-PAzo8-S and Rh-PAzo6-S were used to study the controlled release of the dye in intracellular media. Nanoparticles were not toxic for HeLa cells and endocytosis-mediated cell internalisation was confirmed by confocal microscopy. Furthermore, the possible use of capped materials as a drug-delivery system was demonstrated by the preparation of a new mesoporous silica nanoparticle functionalised with PAzo6 and loaded with the cytotoxic drug camptothecin (CPT-PAzo6-S). Following cell internalisation and lysosome resident enzyme-dependent gate opening, CPT-PAzo6-S induced CPT-dependent cell death in HeLa cells., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)