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Capillary malformation-arteriovenous malformation is a rare autosomal dominant disorder associated with EPHB4 loss-of-function mutations. We report the unique presentation of a 6-year-old girl with multiple capillary malformations in a unilateral segmental distribution affecting the right hemiface, right upper chest, and right arm associated with overgrowth. Targeted next-generation sequencing on a tissue sample revealed a novel heterozygotic variant in the EPHB4 gene (NM_004444.5 (EPHB4): c.715T>A, p.[Cys239Ser]). This case highlights a distinct presentation of CM-AVM type 2 and showcases a new variant in EPHB4 not previously reported in the literature., (© 2023 Wiley Periodicals LLC.)

Objectives: Observational studies have suggested that a higher 25-hydroxyvitamin D concentration may be associated with longer telomere length; however, this has not been investigated in randomised controlled trials. We conducted an ancillary study within a randomised, double-blind, placebo-controlled trial of monthly vitamin D (the D-Health Trial) for the prevention of all-cause mortality, conducted from 2014 to 2020, to assess the effect of vitamin D supplementation on telomere length (measured as the telomere to single copy gene (T/S) ratio)., Design, Setting, Participants, and Intervention: Participants were Australians aged 60-84 years and we randomly selected 1,519 D-Health participants (vitamin D: n=744; placebo: n=775) for this analysis. We used quantitative polymerase chain reaction to measure the relative telomere length (T/S ratio) at 4 or 5 years after randomisation. We compared the mean T/S ratio between the vitamin D and placebo groups to assess the effect of vitamin D supplementation on relative telomere length, using a linear regression model with adjustment for age, sex, and state which were used to stratify the randomisation., Results: The mean T/S ratio was 0.70 for both groups (standard deviation 0.18 and 0.16 for the vitamin D and placebo groups respectively). The adjusted mean difference (vitamin D minus placebo) was -0.001 (95% CI -0.02 to 0.02). There was no effect modification by age, sex, body mass index, or predicted baseline 25-hydroxyvitamin D concentration., Conclusion: In conclusion, routinely supplementing older adults, who are largely vitamin D replete, with monthly doses of vitamin D is unlikely to influence telomere length., Competing Interests: PM Webb has funding from Astra Zeneca for an unrelated study of ovarian cancer. PR Ebeling reports grants and other from Amgen, other from Sanofi, grants and other from Novartis, grants from Eli-Lilly, and grants from Alexion. RE Neale has funding from Viatris for an unrelated study of pancreatic cancer. All other authors declare no competing interests.

Introduction: Surgical treatment of basal cell carcinomas is often performed by physicians with different surgical backgrounds. Collecting data from different surgical departments would better reflect their real-life surgical management. Objectives: To identify the rate, recurrence risk, and predictive factors accordingly to their relative contribution for an incomplete basal cell carcinoma excision in a large multidisciplinary real-life setting Methods: Retrospective cohort study of 2305 surgically treated lesions in different departments of a tertiary center. Results: There was a rate of incomplete excisions (15%) and a recurrence rate (35.5% vs. 6.8% in incomplete vs. complete excisions ( p  < .001)). A third of incompletely excised basal cell carcinoma (BCC) will recur over time. Stratified by relevancy, high-risk histological subtypes (micronodular (OR 5.10 - p  < .001) and morpheaform (OR 5.42 - p  < .001), smaller specimen sizes ( <0.5 cm or 0.5-1 cm, OR 3.99 and 2.49, respectively, p  < .001) high-risk locations (OR 3.06 on the nose, OR 2.77 on the eyelids, p  < .001), and recurrent BCCs (OR 1.72, p  < .001). are the best predictors of an incomplete excision. Conclusions: Acknowledging the rate, recurrence risk and predictive factors for incomplete excisions may be beneficial for optimal preoperative planning and to prevent unwarranted re-interventions, morbidity, and healthcare costs.

The question of whether gold (Au) is more toxic as nanoparticles or in its ionic form remains unclear and controversial. The present work aimed to clarify the effects of 96 h exposure to 4, 80 and 1600 μg·L -1 of 7 nm gold nanoparticles (AuNPs) - (citrate coated (cAuNPs) or polyvinylpyrrolidone coated (PVP-AuNPs)) - and ionic Au (iAu) on gilthead seabream (Sparus aurata). Effects at different levels of biological organization (behaviour, neurotransmission, biotransformation, oxidative stress/damage and genotoxicity) were assessed. cAuNPs induced oxidative stress and damage (lipid peroxidation increase), even at 4 μg·L -1 , and reduced the ability of S. aurata to swim against a water flow at 1600 μg·L -1 . Exposure to cAuNPs induced more adverse effects than exposure to PVP-AuNPs. All tested concentrations of Au (nano or ionic form) induced DNA breaks and cytogenetic damage in erythrocytes of S. aurata. Generally, iAu induced significantly more effects in fish than the nano form, probably associated with the significantly higher accumulation in the fish tissues. No fish mortality was observed following exposure to AuNPs, but mortality was observed in the group exposed to 1600 μg·L -1 of iAu., 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 © 2020 Elsevier B.V. All rights reserved.)

People punish transgressors with different intensity depending if they are members of their group or not. We explore this in a cross-sectional analytical study with paired samples in children with developmental disorders who watched two videos and expressed their opinion. In Video-1, a football-player from the participant's country scores a goal with his hand. In Video-2, a player from another country does the same against the country of the participant. Each subject watched the two videos and their answers were compared. The autism spectrum disorder (ASD) group showed negative feelings in Video 1 (M = - .1; CI 95% - .51 to .31); and in Video 2 (M = - .43; CI 95% .77 to - .09; t(8) = 1.64, p = .13), but the attention deficit hyperactivity disorder, learning disabilities, intellectual disability groups showed positive opinion in Video-1 and negative in Video-2. This suggests that children with ASD respect rules regardless of whether those who break them belong or not to their own group, possibly due to lower degrees of empathy.

Pollution of coasts by toxic metals and metalloids is a worldwide problem for which phytoremediation using halophytes and associated microbiomes is becoming relevant. Metal(loid) excess is a constraint for plant establishment and development, and plant growth promoting rhizobacteria (PGPR) mitigate plant stress under these conditions. However, mechanisms underlying this effect remain elusive. The effect of toxic metal(loid)s on activity and gene expression of ROS-scavenging enzymes in roots of the halophyte Spartina densiflora grown on real polluted sediments in a greenhouse experiment was investigated. Sediments of the metal-polluted joint estuary of Tinto and Odiel rivers and control, unpollutred samples from the Piedras estuary were collected and submitted to ICP-OES. Seeds of S. densiflora were collected from the polluted Odiel marshes and grown in polluted and unpolluted sediments. Rhizophere biofilm-forming bacteria were selected based on metal tolerance and inoculated to S. densiflora and grown for 4 months. Fresh or frozen harvested plants were used for enzyme assays and gene expression studies, respectively. Metal excess induced SOD (five-fold increase), whereas CAT and ascorbate peroxidase displayed minor induction (twofold). A twofold increase of TBARs indicated membrane damage. Our results showed that metal-resistant PGPR (P. agglomerans RSO6 and RSO7 and B. aryabhattai RSO25) contributed to alleviate metal stress, as deduced from lower levels of all antioxidant enzymes to levels below those of non-exposed plants. The oxidative stress index (OSI) decreased between 50 and 75% upon inoculation. The results also evidenced the important role of PAL, involved in secondary metabolism and/or lignin synthesis, as a pathway for metal stress management in this halophyte upon inoculation with appropriate PGPR, since the different inoculation treatments enhanced PAL expression between 3.75- and five-fold. Our data confirm, at the molecular level, the role of PGPR in alleviating metal stress in S. densiflora and evidence the difficulty of working with halophytes for which little genetic information is available., (© 2018 German Society for Plant Sciences and The Royal Botanical Society of the Netherlands.)

A profound analysis of A. tripolium photochemical traits under salinity exposure is lacking in the literature, with very few references focusing on its fatty acid profile role in photophysiology. To address this, the deep photochemical processes were evaluated by Pulse Amplitude Modulated (PAM) Fluorometry coupled with a discrimination of its leaf fatty acid profile. Plants exposed to 125-250 mm NaCl showed higher photochemical light harvesting efficiencies and lower energy dissipation rates. under higher NaCl exposure, there is evident damage of the oxygen evolving complexes (OECs). On the other hand, Reaction Centre (RC) closure net rate and density increased, improving the energy fluxes entering the PS II, in spite of the high amounts of energy dissipated and the loss of PS II antennae connectivity. Energy dissipation was mainly achieved through the auroxanthin pathway. Total fatty acid content displayed a similar trend, being also higher under 125-250 mm NaCl with high levels of omega-3 and omega-6 fatty acids. The increase in oleic acid and palmitic acid allows the maintenance of the good functioning of the PS II. Also relevant was the high concentration of chloroplastic C16:1t in the individuals subjected to 125-250 mm NaCl, related with a higher electron transport activity and with the organization of the Light Harvesting Complexes (LHC) and thus reducing the activation of energy dissipation mechanisms. All these new insights shed some light not only on the photophysiology of this potential cash-crop, but also highlight its important saline agriculture applications of this species as forage and potential source of essential fatty acids., (© 2016 German Botanical Society and The Royal Botanical Society of the Netherlands.)

Background: Vitamin D, specifically serum 25(OH)D has been associated with mortality, cancer and multiple other health endpoints in observational studies, but there is a paucity of clinical trial evidence sufficient to determine the safety and effectiveness of population-wide supplementation. We have therefore launched the D-Health Trial, a randomized trial of vitamin D supplementation for prevention of mortality and cancer. Here we report the methods and describe the trial cohort., Methods: The D-Health Trial is a randomized placebo-controlled trial, with planned intervention for 5years and a further 5years of passive follow-up through linkage with health and death registers. Participants aged 65-84years were recruited from the general population of Australia. The intervention is monthly oral doses of 60,000IU of cholecalciferol or matching placebo. The primary outcome is all-cause mortality. Secondary outcomes are total cancer incidence and colorectal cancer incidence., Results: We recruited 21,315 participants to the trial between February 2014 and May 2015. The participants in the two arms of the trial were well-balanced at baseline. Comparison with Australian population statistics shows that the trial participants were less likely to report being in fair or poor health, to be current smokers or to have diabetes than the Australian population. However, the proportion overweight or with health conditions such as arthritis and angina was similar., Conclusions: Observational data cannot be considered sufficient to support interventions delivered at a population level. Large-scale randomized trials such as the D-Health Trial are needed to inform public health policy and practice., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Cold and heat waves are phenomenon that occurs in higher frequency and intensity due to global climate changes. Commonly cultivated crop species are crucially affected by extreme weather events, and therefore alternative crops - such as halophytes - gain in agricultural interest. While halophytes are potentially able to cope with temperature extremes on the long term exposure, effects of temporary events such as cold and heat waves are not yet described. In order to unveil the effects of these altered thermal environments, Aster tripolium plants were subjected to cold (9/5 °C) and heat (42/38 °C) waves regimes during 3 days and its photochemical and biochemical traits evaluated. In the potential cash crop A. tripolium cold waves induced the gene expression of dehydrins in order to counteract desiccation and thus to prevent oxidative stress. Regulatory proteins on the RNA maturation level (Maturase K) were highly expressed. Heat stress induced the gene expression of the cystein protease gene; most likely to degrade misfolded proteins temporary. Both thermal treatments decreased the photosynthetic efficiency and capacity, driven by a loss in the connectivity between PSII antennae. Nevertheless the light absorption capacity was unaffected due to an increased RC closure net rate. Cold wave-treated individuals showed a decrease in the carotenoid pigmentation, except auroxanthin. In cold wave treated individuals the overall peroxidase activity was significantly increased. Data suggest that exposure to both, cold and heat wave treatment decreased the ecophysiological capacity of A. tripolium., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Waterlogging and submergence are the major constraints to which wetland plants are subjected, with inevitable impacts on their physiology and productivity. Global warming and climate change, as driving forces of sea level rise, tend to increase such submersion periods and also modify the carbonate chemistry of the water column due to the increased concentration of CO2 in the atmosphere. In the present work, the underwater O2 fluxes in the leaves of two abundant Mediterranean halophytes were evaluated at different levels of dissolved CO2. Photosynthetic enhancement due to increased dissolved CO2 was confirmed for both Halimione portulacoides and Spartina maritima, probably due to high tissue porosity, formation of leaf gas films and reduction of the oxygenase activity of Rubisco. Enhancement of the photosynthetic rates in H. portulacoides and S. maritima was concomitant with an increase in energy trapping and transfer, mostly due to enhancement of the carboxylation reaction of Rubisco, leading to a reduction of the energy costs for carbon fixation. Transposing these findings to the ecosystem, and assuming increased dissolved CO2 concentration scenarios, the halophyte community displays a new ecosystem function, increasing the water column oxygenation and thus reinforcing their role as principal primary producers of the estuarine system., (Published by Oxford University Press on behalf of the Annals of Botany Company.)

Juncus acutus arises as possible hyperaccumulator specie, tolerating exogenous Zn concentrations as high as 60 mM. Zinc concentrations here detected in seedlings germinated in the presence high Zn concentrations, were above the described upper toxic levels for higher plants. Even at the highest Zn concentration, growth inhibition only accounted to approximately 30% of control seedlings biomass, presenting an EC₅₀ value in the range of 10-20 mM of metal. PSII quantum yields showed a marked decline, reflection of changes in the thylakoid structure on the PSII electron donor sites. In fact, the electron transport rate was severely affected by Zn in seedlings exposed to higher Zn concentrations leading to a decrease in their maximum electronic transport rate and consequently presenting lower light saturation and lower photosynthetic efficiencies. Although light absorption capacity was not affected by Zn exposure and uptake, energy trapping flux in the photosynthetic apparatus and transport throughout the electronic chain was severely impaired. This lack of efficiency is related with non-functional Zn-chlorophylls formation. There was a strong linear correlation between exogenous Zn concentration applied and the concentration actually verified in the seedlings tissue with the concentration of both ZnChl a and b. There was also a gradual loss of connectivity between the antennae of the PSII units being this more evident at the higher Zn concentrations and thus impairing the energetic transport. The reduction in light harvesting efficiency, leads inevitably to the accumulation of redox energy inside the cells. To counteract ROS generation, all anti-oxidant enzymatic activities (except catalase) showed a proportional response to exogenous and in vivo Zn concentrations. Not only this plant appears to be highly tolerant to high Zn concentrations, but also it can overcome efficiently the damage produced during this uptake by efficiently dissipating the excessive cellular redox potential accumulated, essentially due to Zn incorporation into the chlorophyll molecule., (Copyright © 2014 Elsevier B.V. All rights reserved.)

According the latest predictions, an increase of about two times in atmospheric CO2 concentrations, is expected to occur by the end of this century. In order to understand the effects of this atmospheric composition changes on two abundant Mediterranean halophytes (Halimione portulacoides and Spartina maritima), mesocosmos trials were performed simulating two atmospheric CO2 environments (380 ppm and 760 ppm of CO2 respectively). The two chosen halophyte species present different metabolic characteristics: H. portulacoides, is a C3 specie while S. maritima is a C4 species. Distinct feedbacks were obtained for each of the studied species. Stable Isotope discrimination showed that both species showed an enhancement of the Rubisco carboxylation capacity and photosynthetic efficiency mostly due to an increase in intracellular [CO2]. In H. portulacoides CO2 fertilization induced an enhancement of ETR and a decrease in non-photochemical quenching and in dissipated energy fluxes. On the other hand the C4 grass S. maritima, already at full capacity, showed no photosynthetic enhancement. In fact this highly productive grass presented lower photosynthetic efficiencies accompanied by increases in dissipated energy fluxes mostly due to reductions in energy flux associated with the transport of reducing power throughout the quinone pool. The accumulation of reducing power led to oxidative stress, and thus the photosynthetic ability of this grass was greatly reduced. Both these feedbacks to realistic future CO2 concentrations are important consideration for in future primary productivity models, indicating a possible reduced abundance of the pioneer S. maritima and an increased biomass spreading of the sediment stabilizer H. portulacoides, inevitably affecting the morphology and function of the salt marshes imposed by these atmospheric changes, both in terms of ecosystem functioning and loss of biodiversity., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Submergence is one of the major constrains affecting wetland plants, with inevitable impacts on their physiology and productivity. Global warming as a driving force of sea level rise, tend to increase the submersion periods duration. Photosynthesis biophysical probing arise as an important tool to understand the energetics underlying plant feedback to these constrains. As in previous studies with Spartina maritima, there was no inhibition of photosynthetic activity in submerged individuals. Comparing both donor and acceptor sides of the PSII, the first was more severely affected during submersion, driven by the inactivation of the OEC with consequent impairment of the ETC. Although this apparent damage in the PSII donor side, the electron transport per active reaction centre was not substantially affected, indicating that this reduction in the electron flow is accompanied by a proportional increase in the number of active reaction centres. These conditions lead to the accumulation of excessive reducing power, source of damaging ROS, counteracted by efficient energy dissipation processes and anti-oxidant enzymatic defences. This way, S. maritima appears as a well-adapted species with an evident photochemical plasticity towards submersion, allowing it to maintain its photosynthetic activity even during prolonged submersion periods., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Halimione portulacoides and Sarcocornia fruticosa commonly exhibit a reddish coloration especially in high evaporation periods, due to betacyanin production in response to stress. Although sharing the same area in salt marshes, they present different strategies to overcome salinity stress. While S. fruticosa present a dilution strategy, increasing succulence, H. portulacoides appears to have developed an ionic compartmentalization strategy. Nevertheless, there's still a decrease in the photosynthetic activity in different extents. While in S. fruticosa, the impairment of photosynthetic activity is due to a decrease in the flow from the electron transport chain to the quinone pool; in H. portulacoides the process is affected far more early, with high amounts of energy dissipated at the PSII light harvesting centers. This photosynthetic impairment leads to energy accumulation and consequently to the production of reactive oxygen species (ROS). SOD was particularly active in stressed individuals, although this increment is rather more significant in S. fruticosa than in H. portulacoides suggesting that H. portulacoides may have a maximum salt concentration at which can sustain cellular balance between ROS production and scavenging. These different ecophysiological responses have great importance while evaluating the impacts climate change driven increase of sediment salinity on halophyte physiology and on the marsh community and ecosystem services., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Particulate metal concentrations were assessed before, during and after a flood episode in the Tagus estuary. Particulate metal concentrations showed a decrease during the flood period and very similar values in the months before and after the flood event. Before this period, sampling station characteristics were verified to be homogenous during the peak of the flooding event, as all of the sampling stations assumed very specific characteristics. One of the main consequences from the flood, concurrent with a decrease in particulate metal concentrations, was the high input of SPM into the estuarine area. This finding indicates higher levels of heavy metals in fine-sized particles at low SPM concentration than those present in coarser particles at high SPM levels. These periodic flood events can be considered as estuarine contamination masks and should be interpreted as periods of dilution in heavy metal contamination rather than as an estuarine cleansing process., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The in situ reduction of Cr (VI) to its less toxic form Cr (III) may be a useful detoxification mechanism for phytoremediation. Using a hydroponics mesocosmos approach, we evaluated the ability of Halimione portulacoides to reduce and uptake Cr (VI) and its anti-oxidative feedback and biomarkers. It was found that this specie can, not only reduce large amounts of Cr (VI) in the external medium, but also withdrawn and accumulate this element in its roots and aboveground organs. Both these mechanisms were found to be dose dependent. Jointly with this phytoremediative potential the oxidative feedback was also assessed. Chromium uptake had its major implications on the chlorophyll content and flavonoid content, with potential consequences in the photosynthetic and photo-protective mechanisms. Although the high Cr root accumulation in H. portulacoides, there were no inactivation of the enzymatic defenses, allowing a continuous defense against reactive oxygen species. In fact, GPX and specially SOD revealed to be an excellent dose-related biomarker of Cr induced stress. All these aspects make this specie suitable for Cr (VI) phytoremediation processes, either by phytoextraction or by reduction of Cr (VI) to Cr (III) and also for monitoring programs using SOD and GPX as biomarkers of Cr environmental contamination., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Leaf senescence is the final phase of the leaf development, comprising several controlled complex physiological, biochemical and molecular events. From February to June it was possible to observe a rapid increase of Scirpus maritimus biomass accompanied by an increase in the overall pigment battery, photosynthetic efficiency and photoprotection capacity. With senescence progressing, the photosynthetic pigments decreased dramatically in a rather equal extent. With the exception of Zeaxanthin (90% decrease), all pigments suffered a 98-100% decreased during senescence. Overlooking the operational PSII quantum efficiency it was possible to observe that it suffered almost no changes during leaf maturation (with the exception of the senescent leaves), whilst the maximum quantum efficiency, showed more evident changes, decreasing with the leaf maturation. This observation coupled with the increased DES index may be an indication that the decrease in the PSII maximum yield may represent a mechanism to down-regulate the photosynthetic electron transport rate compensating the consequent decrease in CO(2) assimilation capacity. This fact allied with a decrease in the minimum light intensity for photosynthesis saturation in senescent leaves, suggest that the requirement for reducing power and photophosphorylation for the dark reaction is inevitably decreased and that photosynthesis in senescent leaves will be saturated., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Polymorphous low-grade adenocarcinoma (PLGA) is a rare, malignant salivary gland tumor, which is found almost exclusively in minor salivary glands, primarily those in the palate. We report a case of PLGA arising from minor salivary gland of the palate in a 63-year-old female patient. The tumor was resected through the oral cavity performing a bilateral maxillectomy and surgical defect was reconstructed using a free radial forearm flap combined with iliac crest bone graft. The patient was free of disease at 48 months follow-up. The histopathological features of PLGA, the importance of differential diagnosis from pleomorphic adenoma and adenoid cystic carcinoma and the type of reconstruction are discussed in this article.

Background: Basal epidermolysis bullosa simplex (EBS) is a group of blistering genodermatoses mostly caused by mutations in the keratin genes, KRT5 and KRT14. Recessive mutations represent about 5% of all EBS mutations, being common and specific in populations with high consanguinity, where affected patients show severe phenotypes., Objectives: To accomplish the first mutational analysis in patients of Spanish origin with EBS and to delineate a comprehensive genotype-phenotype correlation., Methods: Twenty-one EBS families were analysed. Immunofluorescence mapping at the dermoepidermal junction level was performed on skin biopsies from patients. Mutation screening of the entire coding sequences of KRT5 and KRT14 in genomic DNA was assessed by polymerase chain reaction and direct sequencing., Results: KRT5 or KRT14 causative mutations were identified in 18 of the 21 EBS families. A total of 14 different mutations were disclosed, of which 12 were dominant missense mutations and two truncating recessive mutations. Five of the 14 mutations were novel including three dominant in KRT5 (p.V186E, p.T321P and p.A428T) and two recessive in KRT14 (p.K116X and p.K250RfsX8). The two patients with EBS carrying homozygous recessive mutations were affected by severe phenotypes and belonged to consanguineous families. All five families with the EBS Dowling-Meara subtype carried recurrent mutations affecting the highly conserved ends of the α-helical rod domain of K5 and K14. The seven mutations associated with the localized EBS subtype were widely distributed along the KRT5 and KRT14 genes. Two families with mottled pigmentation carried the P25L mutation in KRT5, commonly associated with this subtype., Conclusions: This study further confirms the genotype-phenotype correlation established for EBS in other ethnic groups, and is the first in a Mediterranean country (excluding Israel). This study adds two novel recessive mutations to the worldwide record to date, which includes a total of 14 mutations. As in previous reports, the recessive mutations resulted in a lack of keratin K14, giving rise to a generalized and severe presentation., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists.)

Background: Dystrophic epidermolysis bullosa (DEB) is a genodermatosis caused by mutations in COL7A1. The clinical manifestations are highly variable from nail dystrophy to life-threatening blistering, making early molecular diagnosis and prognosis of utmost importance for the affected families. Mutation identification is mandatory for prenatal testing., Objectives: To conduct the first mutational analysis of COL7A1 in a Spanish cohort, to assess mutation consequences at protein/mRNA level and to establish genotype-phenotype correlations., Methods: Forty-nine Spanish patients with DEB were studied. Antigen mapping was performed on patient skin biopsies. COL7A1 mutation screening in genomic DNA was performed by polymerase chain reaction (PCR) and direct sequencing. Mutation consequences were determined by reverse transcriptase-PCR., Results: Eight patients belonged to three unrelated families with dominant DEB. Forty-one were affected with recessive DEB (RDEB). Specifically, 27 displayed the severe generalized subtype, eight the other generalized subtype and six a localized phenotype (two pretibial, three acral and one inversa). Thirty-five mutations were identified, 20 of which are novel. The pathogenic mutation c.6527insC accounted for 46.3% of Spanish RDEB alleles. A consistent genotype-phenotype correlation was established., Conclusions: Although the COL7A1 database indicates that most DEB mutations are family specific, the pathogenic mutation c.6527insC was highly recurrent in our cohort. This level of recurrence for a single genetic defect has never previously been reported for COL7A1. Our findings are essential to the clinicians caring for patients with DEB in Spain and in the large population of Spanish descendants in Latin America. They also provide geneticists a molecular clue for a priority mutation screening strategy.

Pools of Zn, Cu, Cd and Co in leaf, stem and root tissues of Sarcocornia fruticosa, Sarcocornia perennis, Halimione portulacoides and Spartina maritima were analyzed on a bimonthly basis, in a Tagus estuary salt marsh. All the major concentrations were found in the root tissues, being the concentrations in the aboveground organs neglectable for sediment budget proposes, as seen by the low root-aboveground translocation. Metal annual accumulation, root turnovers and cycling coefficients were also assessed. S. maritima showed the higher root turnovers and cycling coefficients for most of the analyzed metals, making this a phytostabilizer specie. By contrast the low root turnover, cycling coefficient and low root necromass generation makes S. perennis the most suitable specie for phytoremediation processes. Although the high amounts of metal return to the sediments, due to root senescence, salt marshes can still be considered sinks of heavy metals, cycling heavy metals mostly between sediment and root., (Copyright 2009 Elsevier Ltd. All rights reserved.)

The rapid advances associated with the Human Genome Project combined with the development of proteomics technology set the bases to face the challenge of human gene therapy. Different strategies must be evaluated based on the genetic defect to be corrected. Therefore, the re-expression of the normal counterpart should be sufficient to reverse phenotype in single-gene inherited disorders. A growing number of candidate diseases are being evaluated since the ADA deficiency was selected for the first approved human gene therapy trial (Blaese et al., 1995). To cite some of them: sickle cell anemia, hemophilia, inherited immune deficiencies, hyper-cholesterolemia and cystic fibrosis. The approach does not seem to be so straightforward when a polygenic disorder is going to be treated. Many human traits like diabetes, hypertension, inflammatory diseases and cancer, appear to be due to the combined action of several genes and environment. For instance, several wizard gene therapy strategies have recently been proposed for cancer treatment, including the stimulation of the immune system of the patient (Xue et al., 2005), the targeting of particular signalling pathways to selectively kill cancer cells (Westphal and Melchner, 2002) and the modulation of the interactions with the stroma and the vasculature (Liotta, 2001; Liotta and Kohn, 2001).

Adult rats submitted to maternal deprivation (DEP) on post-natal day (pnd) 11 show smaller corticosterone (CORT) response to a saline injection than non-deprived (NDEP) rats, mainly at 30 days of age. In the present study we sought to investigate the pituitary-adrenal axis response of 30-day-old DEP rats to a 5-min open-field session, with lights and sound on. Hormone levels were assessed immediately or 20 min after the end of the stress, and were compared to basal levels. The immediate ACTH response of DEP females was the highest; this difference was no longer observed at 20 min, but hormone levels were still higher than basal. Both males and females showed an augmented CORT secretion immediately after the open field session, although only the response of NDEP females was higher than that of male counterparts. Moreover, DEP females showed a lower CORT response than their NDEP counterparts immediately after the stress. The CORT stress response remained equally elevated in males and females at the 20-min time point. Finally, DEP animals, regardless of the gender, ambulated more in the centre of the open field and displayed less grooming behaviour than NDEP pups, suggesting that DEP rats are less emotional than NDEP animals.

During three months (April to June 1997) 1,238 consecutive pregnant women were studied at the time of delivery at the Madariaga public Hospital. Syphilis was confirmed in 26 (2.1%) women, and 15 cases (57.7%) of congenital syphilis were demonstrated in newborns one of whom was a stillborn. Of the syphilitic women 61.5% were 20 years old (average), 65.4% were single, 19.2% had a stable partner and 15.4% were married; 70% of them had finished elementary school (seven years), but despite this discrete level of instruction and that they were benefited with free health attention, 73% of them had not started or completed the pregnancy control. None of these women acted as sexual workers or were drug users; 57.7% were unemployed and the remainder worked as domestic servants or were still going to school. Menarca started at 13 (average) and the age of the first sexual activity was 15 (average). The distribution of the cases of syphilis within the city area shows four clusters that coincide with the lower income population, but not with marginal groups. The failure to submit to medical control during pregnancy among syphilitic women is directly linked with an increased risk for congenital syphilis. The specific prevalence of syphilis in women (20 years old or less) pregnant or not, shows an alarming hidden epidemic situation. An interinstitutional and communitary program, with direct interventions within the detected population clusters, is now underway in order to control syphilis. Undesired pregnancy and syphilis seem to be associated with adolescent unsafe sex conducts. A coordinated program between Public Health Service and National Misiones University is operating, visiting home by home, in order to decrease or eliminate congenital syphilis and is considered a priority health problem. Unfortunately, if sexual conducts do not undergo changes in the near future, at least by the correct use of condoms, HIV will replace syphilis.

Since the initial description of the radial arteriovenous (AV) shunt, hemodialysis has played a primary role in the survival of patients with chronic renal failure. However, it is not unusual to be confronted with patients on chronic hemodialysis who have exhausted all superficial venous access sites. We describe a technique using the deep veins of the arms the outflow system during AV graft construction. By anastomosing the venous limb of the graft to the larger of the two brachial veins, we have been able to give patients AV access when the superficial veins have been exhausted. We have performed this technique with good success in 12 patients. Further experience and longer follow-up are needed.

Purpose: Actinomyces israelii are normal inhabitants in the oral cavity and upper intestinal tract of humans. They rarely cause disease and are seldom reported as pathogens. As a pathogen it causes fistulas, sinuses, and may appear as an abdominal mass and/or abscess. The abdominal mass can masquerade as a malignant process that is very difficult to differentiate, often requiring surgical intervention with resection. Because of difficulty in making a preoperative diagnosis, we undertook this review to determine if all patients require surgical intervention and whether other adjunctive modalities may improve preoperative diagnosis., Methods: We report two patients with abdominal actinomycosis, one affecting the sigmoid colon and the other the retroperitoneum, iliac crest region. Both simulated a malignant process and required operations for diagnosis and treatment., Results: As reported, actinomycotic abdominal masses and strictures can be treated by penicillin alone. Long-term medical treatment seems to be very successful and avoids surgical resection. The difficulty is obtaining a definitive diagnosis., Conclusion: The computed tomographic scan is the most helpful diagnostic modality. Appearance of abdominal actinomycosis is usually a contrast enhancing multicystic lesion as was found in these two patients. Needle aspiration cytology can be fairly accurate in obtaining the diagnosis and is recommended for suspicious lesions.

Butorphanol and nalbuphine, narcotic agonist-antagonists were shown to cause no increase in biliary pressure in contrast to morphine in dogs or men. A non-invasive, ultrasonographic technique confirmed that morphine caused constriction of the common bile duct while placebo caused no effect. To prove the lack of constrictive effect of butorphanol and nalbuphine on the common bile duct, the changes in its diameter were measured following placebo or the two agonist-antagonists by ultrasonography. In a double-blind, randomized study, 17 patients undergoing open cholecystectomy were evaluated. No morphine or opioids were allowed for 12 hours prior to the study. After premedication with midazolam and glycopyrrolate, anesthesia was induced by midazolam, 50 micrograms.kg-1 and thiopental, 3.0-5.0 mg.kg-1. Tracheal intubation was facilitated by succinylcholine 1.0 mg.kg-1 and muscle relaxation was maintained with vecuronium. Anesthesia was maintained with isoflurane or enflurane and nitrous oxide in oxygen. After imaging the common bile duct by ultrasonography, placebo, nalbuphine 0.3 mg.kg-1 or butorphanol 40 micrograms.kg-1 were injected intravenously. The diameter of the common bile duct was measured before and at 4 and 8 minutes after drug administration. One-way analysis of variance and paired t-test were utilized for statistical analysis. P < 0.05 was considered significant. No significant changes in the common bile duct diameter was observed after placebo administration, nor was any change observed after either nalbuphine or butorphanol as compared to the baseline. The comparison of three groups of patients showed no statistically significant difference.(ABSTRACT TRUNCATED AT 250 WORDS)

Although the increase in the common bile duct pressure in response to morphine has been repeatedly reported in experimental animals and humans, this is the first double-blind non-invasive, ultrasonographic study designed to demonstrate constriction of the common bile duct caused by i.v. administration of morphine in surgical patients. In a double-blind, placebo-controlled, randomized study, 12 patients undergoing open cholecystectomy were enrolled. No opioids were allowed for 12 hours prior to the study. After premedication with midazolam and glycopyrrolate, anesthesia was induced by midazolam, 50 micrograms/kg-1 and thiopental, 3.0-5.0 mg/kg-1. Tracheal intubation was facilitated by succinylcholine, 1.0 mg/kg-1 and muscle relaxation was maintained with vecuronium. Anesthesia was maintained with enflurane and nitrous oxide in oxygen. After imaging the common bile duct by ultrasonography, placebo or morphine, 0.2 mg/kg-1 was injected intravenously. The diameter of the common bile duct was measured before and 4 and 8 minutes after the drug. Student t-test was utilized for statistical analysis. P < 0.05 was considered significant. No significant change in common bile duct diameter was observed after placebo administration. Morphine caused a significant reduction in the diameter of the common bile duct. Before morphine, the mean +/- SD diameter was 9.5 +/- 3.3 mm; after morphine at 4 and 8 minutes, 7.2 +/- 2.1 and 5.8 +/- 2.1 mm, respectively. It is concluded that ultrasonography in a double-blind placebo-controlled design has proven to be a valid method for the evaluation of the effect of drugs on the common bile duct.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloidosis is an intriguing disorder. Its clinical presentation usually rests on the organ(s) infiltrated with the amyloid. We report a patient who presented with peritonitis secondary to a perforated large jejunal diverticulum and multiple small bowel diverticula. We believe the diverticula were a direct result of primary amyloid infiltration of the intestine in the antimesenteric location. This is the first reported case of small bowel diverticula caused by amyloidosis.

Duodenal diverticula are present in up to 20 per cent of the population but few patients require surgery for acute complications. Perforation is the rarest of these complications; only 101 affected patients have been reported in the world literature. These reports of perforated duodenal diverticulum are reviewed and strategies for the diagnosis and management of this unusual condition are discussed.

Volvulus is a rare cause of intestinal obstruction in the U.S. Sigmoid colon volvulus is the most frequent, followed by cecal volvulus. The simultaneous occurrence of cecal and sigmoid colon volvulus is extremely unusual. We are reporting what to our knowledge is the third case.

A recent case of posttraumatic splenic abscess in an HIV-positive intravenous drug abuser following a splenic salvage procedure is reported. With the recent trend toward splenic preservation and the ever-increasing population of HIV-positive, immune-compromised patients, the complication of splenic abscess may become more common.

The rodless, end-loop stoma was developed as an alternative to the more traditional loop stoma to minimize patient management problems. A retrospective review of our seven-year experience in 229 patients with end-loop colostomies (135), ileocolostomies (70), and ileostomies (24) is presented. A total of 30 stoma-related complications were observed in 27 stomas, for an overall complication rate of 13.1 percent. The most common complications were skin excoriation secondary to leakage (3.5 percent), retraction (3.5 percent), partial necrosis (2.6 percent), and peristomal sepsis (1.8 percent). Mucocutaneous separation, prolapse, and stenosis were each seen in less than one percent of patients. No cases of stomal herniation, obstruction, or hemorrhage were encountered. Twelve deaths occurred, but none was attributed to stoma-related complications. The rodless, end-loop stoma is a simple and safe procedure with many advantages and a low incidence of complications.

Local hepatic tuberculosis without active pulmonary or miliary tuberculosis is an uncommon diagnosis. Even less common is the finding of tuberculoma or tuberculous liver abscess without clinical evidence of tuberculosis elsewhere. Since 1950, 21 cases of isolated tuberculoma or tuberculous abscess of the liver have been reported in the world literature. We report an additional two cases, one tuberculoma and one with multiple tuberculous abscesses. The case reports illustrate the difficulty in reaching the correct diagnosis, unsuspected in nearly all cases and most often confused with carcinoma of the liver. The correct diagnosis was made by histology, identification of acid-fast organisms by smear, and by cultures of Mycobacterium tuberculosis, but required laparotomy in 19 of the 23 cases. A greater awareness of this rare clinical entity may prevent needless surgical intervention since the vast majority of patients respond well to antituberculous chemotherapy.

Thrombosis of the aorta and inferior vena cava is a rare sequela of blunt abdominal trauma. Inferior vena caval thrombosis developed in a 55-year-old man after blunt abdominal trauma. It was detected 18 days after injury through the use of computed tomography. The patient was treated with a Greenfield filter and anticoagulation.

Thirty-nine patients with primary hyperparathyroidism were studied four to eight years after their initial operation. In six patients, both the pathologist and surgeon agreed on the diagnosis of solitary adenoma; in 16 patients, the surgeon diagnosed solitary adenoma and the pathologist parathyroid hyperplasia (microscopic hyperplasia). In 16 patients, primary chief cell hyperplasia was agreed upon by the pathologist and surgeon. In the 16 patients with microscopic hyperplasia, there have been no long-term recurrences of hypercalcemia, but, in two patients, plasma parathyroid hormone levels are high. Parathyroid hormone--total calcium regression curves demonstrate significant preoperative correlation in solitary adenoma, p less than 0.01, and primary chief cell hyperplasia, p less than 0.05. After operation, significant correlations were not found between parathyroid hormone and total calcium. T-testing slope differences of pre- and postoperative parathyroid hormone--total calcium regression curves demonstrates a significant (p less than 0.01) shift to the right of the microscopic hyperplasia patients after operation, moving them to a broader range of total calcium per picogram parathyroid hormone. We conclude that 1) in primary hyperparathyroidism, positive regulation of total calcium by autonomously released parathyroid hormone exists in patients with solitary adenoma and chief cell hyperplasia; 2) autonomously functioning parathyroid tissue has been removed by operation for solitary adenoma with coexistent microscopic parathyroid hyperplasia. In this four- to eight-year follow-up period, it is clear that microscopic parathyroid hyperplasia is not associated with recurrent hypercalcemia. Two functionally distinct forms of parathyroid suppression are suggested; positively regulated microscopic hyperplasia and negatively regulated pathologically suppressed glands.

This is a descriptive and evaluative report regarding a clinical pharmacy residency in-house on-call program that facilitates the provision of 24-hour clinical pharmacy consultative services within the emergency department. During the two-year evaluation period, clinical pharmacy residents completed 3.1 consultations per 14-hour call period. Additionally, greater than 90% of the clinical pharmacy recommendations were accepted and completely followed by physician cohorts. These consultations were usually solicited by internal medicine physicians within the emergency department, involved patient-specific drug therapy recommendations, and required about 100 minutes (mean per consultation) of the clinical pharmacist's time. Thus, clinical pharmacy consultative services can be a useful addition to health care within the emergency department in teaching hospitals.