Efficacy of Elexacaftor-Tezacaftor-Ivacaftor on chronic rhinosinusitis in cystic fibrosis.

PURPOSE: Our work aims to add evidence on the effectiveness of Elexacaftor-Tezacaftor-Ivacaftor on chronic rhinosinusitis in cystic fibrosis. MATERIALS AND METHODS: We conducted an observational retrospective cohort study at the Cystic Fibrosis Center of a tertiary care hospital to investigate the effect of Elexacaftor-Tezacaftor-Ivacaftor on chronic rhinosinusitis in cystic fibrosis patients, aged 12 or older. The study's endpoints were the change in the occurrence of acute exacerbations of chronic rhinosinusitis, and the variation of the endoscopic and radiologic findings scored using the Lund-Kennedy endoscopic scale, Lund-Mackay, and modified Lund-Mackay radiologic scales, in patients who underwent both pre-treatment and post-treatment examinations. RESULTS: The study population comprised 136 patients, of which 28 underwent both pre-treatment and post-treatment nasal endoscopy and 15 had pre- and post-treatment CT scans. Elexacaftor-Tezacaftor-Ivacaftor provided a significant improvement in chronic rhinosinusitis. The mean number of acute exacerbations of chronic rhinosinusitis per year in the pre-treatment time was 0.55 versus 0.35 during the treatment (p < 0.0021). The Lund-Kennedy scale had a pre-treatment average score of 4.21 points versus 1.5 points after the start of Elexacaftor-Tezacaftor-Ivacaftor (p < 0.0001). The average Lund-Mackay and modified Lund-Mackay scores in the pre-treatment time were respectively 14.6 and 16.45 points; and after the start of the therapy, they became 5.87 and 6.73 (p < 0.0001). CONCLUSION: Elexacaftor-Tezacaftor-Ivacaftor was associated with fewer acute exacerbations of chronic rhinosinusitis, and a significant improvement of chronic rhinosinusitis evaluated endoscopically and radiologically. To our knowledge, this is the first study investigating the change in the occurrence of acute exacerbation of chronic rhinosinusitis in patients affected by cystic fibrosis in therapy with Elexacaftor-Tezacaftor-Ivacaftor.

Urban habitat fragmentation and floral resources shape the occurrence of gut parasites in two bumblebee species.

Urbanization and the expansion of human activities foster radical ecosystem changes with cascading effects also involving host-pathogen interactions. Urban pollinator insects face several stressors related to landscape and local scale features such as green habitat loss, fragmentation and availability reduction of floral resources with unpredictable effects on parasite transmission. Furthermore, beekeeping may contribute to the spread of parasites to wild pollinators by increasing the number of parasite hosts. Here we used DNA-based diagnostics tools to evaluate how the occurrence of parasites, namely microsporidians (Nosema spp.), trypanosomatids (Crithidia spp.) and neogregarines (Apicystis bombi), is shaped by the above-mentioned stressors in two bumblebee species (i.e. Bombus terrestris and Bombus pascuorum). Infection rates of the two species were different and generally higher in B. terrestris. Moreover, they showed different responses towards the same ecological variables, possibly due to differences in body size and foraging habits supposed to affect their susceptibility to parasite infection. The probability of infection was found to be reduced in B. pascuorum by green habitat fragmentation, while increased along with floral resource availability. Unexpectedly, B. terrestris had a lower parasite richness nearby apiaries maybe due to the fact that parasites are prone to be transmitted among the most abundant species. Our finding supports the need to design proper conservation measures based on species-specific knowledge, as suggested by the variation in the parasite occurrence of the two species. Moreover, conservation policies aiming at safeguarding pollinators through flower planting should consider the indirect effects of these measures for parasite transmission together with pollinator biodiversity issues.

Concomitant trauma of brain and upper cervical spine: lessons in injury patterns and outcomes.

PURPOSE: The literature on concomitant traumatic brain injury (TBI) and traumatic spinal injury is sparse and a few, if any, studies focus on concomitant TBI and associated upper cervical injury. The objective of this study was to fill this gap and to define demographics, patterns of injury, and clinical data of this specific population. METHODS: Records of patients admitted at a single trauma centre with the main diagnosis of TBI and concomitant C0-C1-C2 injury (upper cervical spine) were identified and reviewed. Demographics, clinical, and radiological variables were analyzed and compared to those of patients with TBI and: (i) C3-C7 injury (lower cervical spine); (ii) any other part of the spine other than C1-C2 injury (non-upper cervical); (iii) T1-L5 injury (thoracolumbar). RESULTS: 1545 patients were admitted with TBI and an associated C1-C2 injury was found in 22 (1.4%). The mean age was 64 years, and 54.5% were females. Females had a higher rate of concomitant upper cervical injury (p = 0.046 vs non-upper cervical; p = 0.050 vs thoracolumbar). Patients with an upper cervical injury were significantly older (p = 0.034 vs lower cervical; p = 0.030 vs non-upper cervical). Patients older than 55 years old had higher odds of an upper cervical injury when compared to the other groups (OR = 2.75). The main mechanism of trauma was road accidents (RAs) (10/22; 45.5%) All pedestrian injuries occurred in the upper cervical injured group (p = 0.015). ICU length of stay was longer for patients with an upper cervical injury (p = 0.018). Four patients died in the upper cervical injury group (18.2%), and no death occurred in other comparator groups (p = 0.003). CONCLUSIONS: The rate of concomitant cranial and upper cervical spine injury was 1.4%. Risk factors were female gender, age ≥ 55, and pedestrians. RAs were the most common mechanism of injury. There was an association between the upper cervical injury group and longer ICU stay as well as higher mortality rates. Increased understanding of the pattern of concomitant craniospinal injury can help guide comprehensive diagnosis, avoid missed injuries, and appropriate treatment.

Ten-year follow-up of auditory brainstem implants: From intra-operative electrical auditory brainstem responses to perceptual results.

The auditory brainstem implant (ABI) can provide hearing sensation to individuals where the auditory nerve is damaged. However, patient outcomes with the ABI are typically much poorer than those for cochlear implant recipients. A major limitation to ABI outcomes is the number of implanted electrodes that can produce auditory responses to electric stimulation. One of the greatest challenges in ABI surgery is the intraoperative positioning of the electrode paddle, which must fit snugly within the cochlear nucleus complex. While there presently is no optimal procedure for intraoperative electrode positioning, intraoperative assessments may provide useful information regarding viable electrodes that may be included in patients' clinical speech processors. Currently, there is limited knowledge regarding the relationship between intraoperative data and post-operative outcomes. Furthermore, the relationship between initial ABI stimulation with and long-term perceptual outcomes is unknown. In this retrospective study, we reviewed intraoperative electrophysiological data from 24 ABI patients (16 adults and 8 children) obtained with two stimulation approaches that differed in terms of neural recruitment. The interoperative electrophysiological recordings were used to estimate the number of viable electrodes and were compared to the number of activated electrodes at initial clinical fitting. Regardless of the stimulation approach, the intraoperative estimate of viable electrodes greatly overestimated the number of active electrodes in the clinical map. The number of active electrodes was associated with long-term perceptual outcomes. Among patients with 10-year follow-up, at least 11/21 active electrodes were needed to support good word detection and closed-set recognition and 14/21 electrodes to support good open-set word and sentence recognition. Perceptual outcomes were better for children than for adults, despite a lower number of active electrodes.

Mimicking orchids lure bees from afar with exaggerated ultraviolet signals.

Flowers have many traits to appeal to pollinators, including ultraviolet (UV) absorbing markings, which are well-known for attracting bees at close proximity (e.g., <1 m). While striking UV signals have been thought to attract pollinators also from far away, if these signals impact the plant pollinia removal over distance remains unknown. Here, we report the case of the Australian orchid Diuris brumalis, a nonrewarding species, pollinated by bees via mimicry of the rewarding pea plant Daviesia decurrens. When distant from the pea plant, Diuris was hypothesized to enhance pollinator attraction by exaggeratedly mimicking the floral ultraviolet (UV) reflecting patterns of its model. By experimentally modulating floral UV reflectance with a UV screening solution, we quantified the orchid pollinia removal at a variable distance from the model pea plants. We demonstrate that the deceptive orchid Diuris attracts bee pollinators by emphasizing the visual stimuli, which mimic the floral UV signaling of the rewarding model Daviesia. Moreover, the exaggerated UV reflectance of Diuris flowers impacted pollinators' visitation at an optimal distance from Da. decurrens, and the effect decreased when orchids were too close or too far away from the model. Our findings support the hypothesis that salient UV flower signaling plays a functional role in visual floral mimicry, likely exploiting perceptual gaps in bee neural coding, and mediates the plant pollinia removal at much greater spatial scales than previously expected. The ruse works most effectively at an optimal distance of several meters revealing the importance of salient visual stimuli when mimicry is imperfect.

DNA metabarcoding unveils the effects of habitat fragmentation on pollinator diversity, plant-pollinator interactions, and pollination efficiency in Maldive islands.

Habitat fragmentation affects biodiversity, but with unclear effects on pollinators and their interactions with plants in anthropized landscapes. Islands could serve as open air laboratories, suitable to disentangle how land-use alteration impacts pollination ecology. In Maldive islands we investigated how pollinator richness, plant-pollinator interactions and pollination efficiency are influenced by the green area fragmentation (i.e., gardens and semi-natural patches). Moreover, we considered the mediating role of pollinator body size and the plant trait of being invasive in shaping interactions. To do this, we surveyed pollinator insects from 11 islands representing a gradient of green area fragmentation. A DNA metabarcoding approach was adopted to identify the pollen transported by pollinators and characterize the plant-pollinator interactions. We found that intermediate levels of green area fragmentation characterized pollinator communities and increased their species richness, while decreasing interaction network complexity. Invasive plants were more frequently found on pollinator bodies than native or exotic noninvasive ones, indicating a concerningly higher potential for pollen dispersal and reproduction of the former ones. Intriguingly, pollinator body size mediated the effect of landscape alteration on interactions, as only the largest bees expanded the foraging diet in terms of plant richness in the transported pollen at increasing fragmentation. In parallel, the pollination efficiency increased with pollinator species richness in two sentinel plants. This study shows that moderate landscape fragmentation of green areas shapes many aspects of the pollination ecosystem service, where despite interactions being less complex and mediated by pollinator body size, pollinator insect biodiversity and potential plant reproduction are supported.

Effect of urbanization and its environmental stressors on the intraspecific variation of flight functional traits in two bumblebee species.

The way urbanization shapes the intraspecific variation of pollinator functional traits is little understood. However, this topic is relevant for investigating ecosystem services and pollinator health. Here, we studied how urbanization affects the functional traits of workers in two bumblebee species (Bombus terrestris and B. pascuorum) sampled in 37 sites along a gradient of urbanization in North Italy (an area of 1800 km2 including the metropolitan context of Milan and other surrounding capital districts). Namely, we investigated the effect of land use composition, configuration, air temperature, flower resource abundance, and air pollutants on the variation of traits related to flight performance and of stress during insect development (i.e., wing size, wing shape and size fluctuating asymmetry). The functional traits of the two bumblebees responded idiosyncratically to urbanization. Urban temperatures were associated with smaller wing sizes in B. pascuorum and with more accentuated fluctuating asymmetry of wing size in B. terrestris. Moreover, flower abundance correlated with bigger wings in B. terrestris and with less asymmetric wing size in B. pascuorum. Other traits did not vary significantly, and other urban variables played minor effects. These species-specific variation patterns highlight that environmental stressor linked to urbanization negatively impact the traits related to flight performance and development stability of these syntopic bumblebees, with possible consequences on the pollination service they provide.

Cauda equina ependymomas: surgical treatment and long-term outcomes in a series of 125 patients.

OBJECTIVE: Cauda equina ependymoma (CEE) is a rare tumor for which little information is available on the oncological and clinical outcomes of patients. In this study the authors aimed to address functional, oncological, and quality-of-life (QOL) outcomes in a large series of consecutive patients operated on at their institution during the past 20 years. METHODS: The records of 125 patients who underwent surgery between January 1998 and September 2018 were reviewed. Analyzed variables included demographic, clinical, radiological, surgical, and histopathological features. Neurological outcomes were graded according to the McCormick and Kesselring scales. The QOL at follow-up was evaluated by administering the EQ-5DL questionnaire. RESULTS: On admission, 84% of patients had a McCormick grade of I and 76.8% had a Kesselring score of 0. At follow-up (clinical 8.13 years; radiological 5.87 years) most scores were unchanged. Sacral level involvement (p = 0.029) and tumor size (p = 0.002) were predictors of poor functional outcome at discharge. Tumor size (p = 0.019) and repeated surgery (p < 0.001) were predictors of poor outcome. A preoperative McCormick grade ≥ III and Kesselring grade ≥ 2 were associated with worse outcomes (p = 0.035 and p = 0.002, respectively). Myxopapillary ependymoma (MPE) was more frequent than grade II ependymoma (EII). The overall rate of gross-total resection (GTR) was 91.2% and rates were significantly higher for patients with EII (98%) than for those with MPE (84%) (p = 0.0074). On multivariate analysis, the only factor associated with GTR was the presence of a capsule (p = 0.011). Seventeen patients (13.7%) had recurrences (13 MPE, 4 EII; 76.4% vs 23.6%; p = 0.032). The extent of resection was the only factor associated with recurrence (p = 0.0023) and number of surgeries (p = 0.006). Differences in progression-free survival (PFS) were seen depending on the extent of resection at first operation (p < 0.001), subarachnoid seeding (p = 0.041), piecemeal resection (p = 0.004), and number of spine levels involved (3 [p = 0.016], 4 [p = 0.011], or ≥ 5 [p = 0.013]). At follow-up a higher proportion of EII than MPE patients were disease free (94.7% vs 77.7%; p = 0.007). The QOL results were inferior in almost all areas compared to a control group of subjects from the Italian general population. A McCormick grade ≥ 3 and repeated surgeries were associated with a worse QOL (p = 0.006 and p = 0.017). CONCLUSIONS: An early diagnosis of CEE is important because larger tumors are associated with recurrences and worse functional neurological outcomes. Surgery should be performed with the aim of achieving an en bloc GTR. The histological subtype was not directly associated with recurrences, but some of the features more commonly encountered in MPEs were. The outcomes are in most cases favorable, but the mean QOL perception is inferior to that of the general population.

Updating the list of flower-visiting bees, hoverflies and wasps in the central atolls of Maldives, with notes on land-use effects.

Maldives islands host a unique biodiversity, but their integrity is threatened by climate change and impacting land-uses (e.g. cemented or agricultural areas). As pollinators provide key services for the ecosystems and for the inhabitants, it is crucial to know which pollinators occur in the islands, to characterise their genetic identity and to understand which plants they visit and the size of the human impact. Given that no significant faunistic surveys of Hymenoptera have been published for the country in more than 100 years and that Syrphidae were only partly investigated, we sampled islands in the central part of the Maldives country (Faafu and Daahlu atolls) and hand-netted flower-visiting bees, wasps and hoverflies (Hymenoptera: Anthophila, Crabronidae, Sphecidae, Vespidae, Scoliidae and Diptera: Syrphidae). Overall, we found 21 species; 76.4% of the collected specimens were Anthophila (bees), 12.7% belonged to several families of wasps and 10.8% of individuals were Syrphidae. It seems that one third of species are new for the Maldives, based on the published literature. Human land-uses seem to shape the local pollinator fauna since the assemblages of bees, wasps and hoverflies from urbanised and agricultural islands differed from those in resort and natural ones. These pollinators visited 30 plant species in total, although some invasive plants hosted the highest number of flower visitor species. Biogeographically, this pollinating fauna is mostly shared with Sri Lanka and India. Genetically, the used marker hinted for a unique fauna in relation to the rest of the distribution ranges in most cases, although generally within the level of intraspecific genetic variation. This study significantly contributes to increasing the knowledge on the pollinator diversity and genetic identity in Maldives islands also considering the important implications for the islands' land-use and the role of invasive plants. This study will be pivotal for future pollination studies and biodiversity conservation efforts in the region.

Assessment of Dietary Bioactive Phenolic Compounds and Agricultural Sustainability of an African Leafy Vegetable Corchorus olitorius L.

Corchorus olitorius L. is an African leafy vegetable of high nutritional interest. To assess its agricultural suitability to sustainable cultivation conditions and its potential benefits for human nutrition, its phytochemical content in response to conservation agriculture practices [i.e., no-tillage (NT) and cover crop maintenance] and low water regime were evaluated and compared with response under conventional agriculture management. Hydric stress and NT did not affect the content of antioxidant metabolites, compared to conventional agricultural practices. In both conditions, leaves were found to be a great source of phenolic compounds. The effect of these phenolic fractions was assessed on two colon cell phenotypes to evaluate putative nutraceutical properties. Polyphenol-enriched extracts (PEEs) displayed selective cytotoxic activities against tumor Caco-2 cells but not on the healthy CCD841 line. PEEs were able to trigger oxidative stress and to inhibit the activity of glutathione-independent antioxidant enzymes on Caco-2 cells. C. olitorius showed to be a promising crop for improving both agricultural sustainability and health benefits due to the great amount of antioxidant compounds in leaves, whose occurrence is not altered by stressful farming conditions. Given its high adaptability, the cultivation of this crop is therefore recommendable also in the Mediterranean Basin.

Combined Impact of No-Till and Cover Crops with or without Short-Term Water Stress as Revealed by Physicochemical and Microbiological Indicators.

Combining no-till and cover crops (NT + CC) as an alternative to conventional tillage (CT) is generating interest to build-up farming systems' resilience while promoting climate change adaptation in agriculture. Our field study aimed to assess the impact of long-term NT + CC management and short-term water stress on soil microbial communities, enzymatic activities, and the distribution of C and N within soil aggregates. High-throughput sequencing (HTS) revealed the positive impact of NT + CC on microbial biodiversity, especially under water stress conditions, with the presence of important rhizobacteria (e.g., Bradyrhizobium spp.). An alteration index based on soil enzymes confirmed soil depletion under CT. C and N pools within aggregates showed an enrichment under NT + CC mostly due to C and N-rich large macroaggregates (LM), accounting for 44% and 33% of the total soil C and N. Within LM, C and N pools were associated to microaggregates within macroaggregates (mM), which are beneficial for long-term C and N stabilization in soils. Water stress had detrimental effects on aggregate formation and limited C and N inclusion within aggregates. The microbiological and physicochemical parameters correlation supported the hypothesis that long-term NT + CC is a promising alternative to CT, due to the contribution to soil C and N stabilization while enhancing the biodiversity and enzymes.

Heavy metal tolerance of orchid populations growing on abandoned mine tailings: A case study in Sardinia Island (Italy).

Understanding how environmental pollutants influence plant occurrence, growth, and development is key for effective management plans and potential bioremediation. Rare plants, such as orchids, may occur in modified habitats and on soils containing heavy metals, yet their ecological and physiological responses to heavy metals is poorly understood. We investigated the influence of heavy metal pollution on orchid growth rates and interactions with soil fungal mutualists by comparing a large population of the orchid Epipactis helleborine (L.) Crantz subsp. tremolsii (Pau) E. Klein that grows on mine tailings in south-west Sardinia (Italy) with a population that grows on non-contaminated soils in central Sardinia. Soils of the contaminated site had high levels of heavy metals and low organic matter and nutritive elements content. We performed a morphological analysis on twenty individuals that have been subjected to measurement of bioaccumulation and translocation of heavy metals. Fungi associated with the roots of plants from the contaminated and uncontaminated site were grown and identified by DNA barcoding approach. Plants from the contaminated site were smaller than the ones growing in the uncontaminated site and were found to be able to tolerate heavy metals from the soil and to accumulate and translocate them into their organs. Fungi belonging to the genus Ilyonectria (Ascomycota) were found both in contaminated and uncontaminated sites, while an unidentified fungus was isolated from roots in the contaminated site only. These results are discussed in terms of orchids' tolerance to heavy metals and its physiological and ecological mechanisms. The role of contaminated habitats in harbouring orchids and peculiar taxa is also discussed.

Correction: Foraging strategies are maintained despite workforce reduction: A multidisciplinary survey on the pollen collected by a social pollinator.

[This corrects the article DOI: 10.1371/journal.pone.0224037.].

Foraging strategies are maintained despite workforce reduction: A multidisciplinary survey on the pollen collected by a social pollinator.

The way pollinators gather resources may play a key role for buffering their population declines. Social pollinators like bumblebees could adjust their foraging after significant workforce reductions to keep provisions to the colony optimal, especially in terms of pollen diversity and quantity. To test what effects a workforce reduction causes on the foraging for pollen, commercially-acquired colonies of the bumblebee Bombus terrestris were allowed to forage in the field and they were experimentally manipulated by removing half the number of workers. For each bumblebee, the pollen pellets were taxonomically identified with DNA metabarcoding of the ITS2 region followed by a statistical filtering based on ROC curves to filter out underrepresented OTUs. Video cameras and network analyses were employed to investigate changes in foraging strategies and behaviour. After filtering out the false-positives, HTS metabarcoding yielded a high plant diversity in the pollen pellets; for plant identity and pollen quantity traits no differences emerged between samples from treated and from control colonies, suggesting that plant choice was influenced mainly by external factors such as the plant phenology. The colonies responded to the removal of 50% of their workers by increasing the foraging activity of the remaining workers, while only negligible changes were found in diet breadth and indices describing the structure of the pollen transport network. Therefore, a consistency in the bumblebees' feeding strategies emerges in the short term despite the lowered workforce.

DNA barcoding to promote social awareness and identity of neglected, underutilized plant species having valuable nutritional properties.

It is estimated that about 7000 plant species and a large number of cultivars and varieties have been cultivated for consumption in human history. However, <0.5% of these currently provide the majority of human food energy needs worldwide (e.g., rice, wheat, maize, and potato). Global issues such as climate change, diffusion of pests, and resistance to agrochemical treatments are posing great concern about the sustainable cultivation of these major staples, especially in equatorial and tropical countries, such as Sub Saharan Africa. In addition, most of these regions contain malnutrition and micronutrient deficiencies, and the sum of such problems create serious implications at social, political, and economic levels. A possible solution relies on the exploitation of plant biodiversity and particularly on the so-called NUS (Neglected and Underutilized Species). These plants are traditionally grown in their centres of origin and continue to be maintained by sociocultural preferences, however they remain inadequately documented and neglected by formal research and conservation programs. Although they are important in terms of micronutrients and the ability to grow in harsh conditions, these species are falling into disuse due to agronomic, genetic, economic, and cultural reasons. To promote and spread their cultivation at the global scale, along with knowledge on their suitability for human nutrition, reliable identification systems are necessary to guarantee adequate authenticity along the entire supply chain and distribution network. A precise identification of the different species and their varieties is fundamental both to retrieve information on their origin and authenticate the raw materials (i.e., seeds, leaves and fruit) and related processed products that can be distributed at the local or global scale. DNA-based techniques can help achieve this mission. In particular, the DNA barcoding approach has gained a role of primary importance due to its universality and versatility. Here, we discuss the advantages in using DNA barcoding for the identification of some of the most representative NUS species, as well as their traceability and conservation of cultural practices around them.

Sustainability Perspectives of Vigna unguiculata L. Walp. Cultivation under No Tillage and Water Stress Conditions.

Nowadays, agriculture is facing the great challenge of climate change which puts the productivity of the crops in peril due to unpredictable rain patterns and water shortages, especially in the developing world. Besides productivity, nutritional values of the yields of these crops may also be affected, especially under low mechanization and the low water availability conditions of the developing world. Conservation agriculture (CA) is a topic of emerging interest due to the provision of adequate yields and reduced environmental impact, such as greenhouse gas emissions, by being based on three main principles: minimum soil disturbance (reduced or no tillage), cover crop maintenance, and crop rotation. The aim of this study was to assess the impact of CA management on the growth performance and the nutritional profile of cowpea (Vigna unguiculata L. Walp), a pulse of African origin, commonly known as black eye bean under field conditions. A field experiment was designed to assess the effect of conventional tillage (CT) and no-tillage (NT) combined with the usage of a set of cover crops, coupled to normal and deficient water regimes. Cowpea was revealed to be able to grow and yield comparably at each level of the treatment tested, with a better ability to face water exhaustion under CA management. After a faster initial growth phase in CT plots, the level of adaptability of this legume to NT was such that growth performances improved significantly with respect to CT plots. The flowering rate was higher and earlier in CT conditions, while in NT it was slower but longer-lasting. The leafy photosynthetic rate and the nutritional profile of beans were slightly influenced by tillage management: only total starch content was negatively affected in NT and watered plots while proteins and aminoacids did not show any significant variation. Furthermore, significantly higher carbon and nitrogen concentration occurred in NT soils especially at the topmost (0-5 cm) soil horizon. These findings confirm the capability of CA to enrich soil superficial horizons and highlight that cowpea is a suitable crop to be grown under sustainable CA management. This practice could be pivotal to preserve soils and to save agronomical costs without losing a panel of nutrients that are important to the human diet. Due to its great protein and aminoacidic composition, V. unguiculata is a good candidate for further cultivation in regions of the word facing deficiencies in the intake of such nutrients, such as the Mediterranean basins and Sub-Saharan countries.

Surgical Management of Adverse Radiation Effects After Gamma Knife Radiosurgery for Cerebral Arteriovenous Malformations: A Population-Based Cohort Study.

OBJECTIVE: The goal of this study is to report our experience in the surgical treatment of cerebral arteriovenous malformations (cAVMs) related permanent symptomatic adverse radiation effects (PSAREs), to clarify an appropriate surgical management and to identify the risk factors related to their development. METHODS: We evaluated 549 patients treated with Gamma Knife radiosurgery (GKRS) for cAVMs with a follow-up of at least 8 years. Univariate and multivariate analyses were used to test different risk factors related to the development of PSARE. We retrospectively reviewed the records of these patients to analyze the clinical outcome. RESULTS: Fourteen patients (2.5%) developed PSARE and were submitted to surgery. Higher average treated volume represents a significant risk factors for the development of PSARE (P < 0.05); on the other hand, older age and higher average dose reduce the risk of PSARE (P < 0.05). A favorable clinical outcome was achieved in 13 patients (93%) after surgery; in 1 patient, the unfavorable outcome was due to hemorrhage that occurred months after GKRS. Serial MRI scans following either surgical removal of the nodule or Ommaya reservoir positioning showed progressive reduction of brain edema in all cases. CONCLUSIONS: The management of PSARE is controversial, especially for cAVMs treated with SRS. Surgical removal is rarely needed, but-if unavoidable-it can be a valuable option in experienced hands. A careful preoperative planning is always necessary to detect pathologic blood flow through the PSARE.

Leksell Gamma Knife for pediatric and adolescent cerebral arteriovenous malformations: results of 100 cases followed up for at least 36 months.

OBJECT: The goal of this study was to evaluate advantages, risks, and failures of Gamma Knife radiosurgery (GKRS) in a large series of pediatric and adolescent patients with cerebral arteriovenous malformations (cAVMs) who were followed up for at least 36 months. METHODS: Since February 1993, 100 pediatric and adolescent patients (≤ 18 years of age) with cAVMs have undergone GKRS at the authors' institution and were followed up for at least 36 months. Forty-six patients were boys and 54 were girls; the mean age was 12.8 years (range 3-18 years). Hemorrhage, either alone or combined with seizure, was the clinical onset in 70% of cases. The mean pre-GK cAVM volume was 2.8 ml; 92% of cAVMs were Spetzler-Martin (S-M) Grades I-III. Most lesions (94%) were in eloquent or deep-seated brain regions, according to S-M classification. The parameters for mean and range in treatment planning were prescription isodose 53.8% (40%-90%); prescription dose (PD) 20.2 Gy (9.0-26.4 Gy); maximal dose (MD) 37.8 Gy (18-50 Gy); and number of shots 4.7 (1-17). On the day of GKRS, stereotactic CT or stereotactic MRI and digital subtraction angiography were used. RESULTS: Obliteration rate (OR) was angiographically documented in 75 of 84 cases (89.3%) after single-session GKRS, with actuarial ORs at 3 and 5 years of 68.0% and 88.1%, respectively. A repeat treatment was performed in 7 patients (6 with obliteration), and 16 patients with cAVMs underwent staged treatment (9 of them were angiographically cured). Thus, the overall OR was 90%, with actuarial ORs at 3, 5, and 8 years of 59.0%, 76.0%, and 85.0%, respectively. Permanent symptomatic GK-related complications were observed in 11% of cases, with surgical removal of enlarged mass seen on post-RS imaging needed in 5 cases. Hemorrhage during the latency period occurred in 9% of patients, but surgical evacuation of the hematoma was required in only 1 patient. One patient died due to rebleeding of a brainstem cAVM. Radiosurgery outcomes varied according to cAVM sizes and doses: volumes ≤ 10 ml and PDs > 16 Gy were significantly associated with higher ORs and lower rates of permanent complication and bleeding during the latency period. CONCLUSIONS: The data from this study reinforce the conclusion that GKRS is a safe and effective treatment for pediatric and adolescent cAVMs, yielding a high OR with minimal permanent severe morbidity and no mortality. The very low frequency of severe hemorrhages during the latency period further encourages a widespread application of RS in such patients. Univariate analysis found that modified RS-based cAVM score, nidus volume, PD, integral dose, S-M grade, and preplanned treatment (the last 2 parameters were also confirmed on multivariate analysis) significantly influenced OR. Lower S-M grades and single-session planned treatments correlated with shorter treatment obliteration interval on univariate analysis. This statistical analysis suggests that a staged radiosurgical treatment should be planned when nidus volume > 10 ml and/or when the recommended PD is ≤ 16 Gy.