Importance of communication of CT indication for imaging yield in patients with gastrointestinal bleed.

PURPOSE: The indications for requesting a diagnostic test are important for the selection and timing of imaging protocols. We sought to evaluate the diagnostic yield and impact on patient disposition when evaluating computed tomography (CT) of the abdomen and pelvis in adult patients presenting with gastrointestinal bleeding (GIB) to the Emergency Department (ED). METHODS: This study was an observational cohort study of consecutive adult ED patients with ICD10 codes related to GIB between 5/5/2018 and 6/1/2020. CT reports were reviewed for indications, exam type and findings. Reports were classified as positive (active bleeding, recent bleeding or suspected etiology for GIB), negative or other significant findings. Methodological guidelines for reporting observational studies were followed (STROBE). RESULTS: Among 943 patients with GIB during the study period, 33% (n = 312) had an abdominopelvic CT ordered. Most CTs included contrast, 64.1% (n = 200) used a single portal venous phase and 28.9% (n = 90) were multi-phase. CT identified active bleeding in 4.2% (n = 13/312) and intraluminal blood in 2.9% (n = 9/312) patients. Patients that had GIB indications on the CT order (n = 142) were more likely to receive a multiphase study compared to those without GIB indication (n = 94) (43.0% vs. 8.5%, difference 34.5%, 95% CI 23.7% to 43.7%, p < 0.0001). Patients that received multiphase studies were more likely to have a source of GIB identified compared to single-phase (18.9% vs 1.5%, OR 15.3, 95% CI 4.4 to 53.7, p < 0.0001). In 40.3% (n = 117/290) of patients without bleeding, an intra-abdominal cause for their symptoms was identified. Those with GIB or with an identified cause were more likely to be admitted. CONCLUSIONS: One-third of patients evaluated in the ED with GIB had a CT ordered. Active GIB was detected more often when multiphase exams were performed. Multiphase exams are done more often if GIB is listed in the CT indication. When a CT is positive, patients are more likely to be admitted or observed. Accurate indications are critical to optimize exam performance.

Redox-Related Proteins in Melanoma Progression.

Melanoma is the most aggressive type of skin cancer. Despite the available therapies, the minimum residual disease is still refractory. Reactive oxygen and nitrogen species (ROS and RNS) play a dual role in melanoma, where redox imbalance is involved from initiation to metastasis and resistance. Redox proteins modulate the disease by controlling ROS/RNS levels in immune response, proliferation, invasion, and relapse. Chemotherapeutics such as BRAF and MEK inhibitors promote oxidative stress, but high ROS/RNS amounts with a robust antioxidant system allow cells to be adaptive and cooperate to non-toxic levels. These proteins could act as biomarkers and possible targets. By understanding the complex mechanisms involved in adaptation and searching for new targets to make cells more susceptible to treatment, the disease might be overcome. Therefore, exploring the role of redox-sensitive proteins and the modulation of redox homeostasis may provide clues to new therapies. This study analyzes information obtained from a public cohort of melanoma patients about the expression of redox-generating and detoxifying proteins in melanoma during the disease stages, genetic alterations, and overall patient survival status. According to our analysis, 66% of the isoforms presented differential expression on melanoma progression: NOS2, SOD1, NOX4, PRX3, PXDN and GPX1 are increased during melanoma progression, while CAT, GPX3, TXNIP, and PRX2 are decreased. Besides, the stage of the disease could influence the result as well. The levels of PRX1, PRX5 and PRX6 can be increased or decreased depending on the stage. We showed that all analyzed isoforms presented some genetic alteration on the gene, most of them (78%) for increased mRNA expression. Interestingly, 34% of all melanoma patients showed genetic alterations on TRX1, most for decreased mRNA expression. Additionally, 15% of the isoforms showed a significant reduction in overall patient survival status for an altered group (PRX3, PRX5, TR2, and GR) and the unaltered group (NOX4). Although no such specific antioxidant therapy is approved for melanoma yet, inhibitors or mimetics of these redox-sensitive proteins have achieved very promising results. We foresee that forthcoming investigations on the modulation of these proteins will bring significant advances for cancer therapy.

Non-Syndromic Intellectual Disability and Its Pathways: A Long Noncoding RNA Perspective.

Non-syndromic intellectual disability (NS-ID or idiopathic) is a complex neurodevelopmental disorder that represents a global health issue. Although many efforts have been made to characterize it and distinguish it from syndromic intellectual disability (S-ID), the highly heterogeneous aspect of this disorder makes it difficult to understand its etiology. Long noncoding RNAs (lncRNAs) comprise a large group of transcripts that can act through various mechanisms and be involved in important neurodevelopmental processes. In this sense, comprehending the roles they play in this intricate context is a valuable way of getting new insights about how NS-ID can arise and develop. In this review, we attempt to bring together knowledge available in the literature about lncRNAs involved with molecular and cellular pathways already described in intellectual disability and neural function, to better understand their relevance in NS-ID and the regulatory complexity of this disorder.

Root-Secreted Coumarins and the Microbiota Interact to Improve Iron Nutrition in Arabidopsis.

Plants benefit from associations with a diverse community of root-colonizing microbes. Deciphering the mechanisms underpinning these beneficial services are of interest for improving plant productivity. We report a plant-beneficial interaction between Arabidopsis thaliana and the root microbiota under iron deprivation that is dependent on the secretion of plant-derived coumarins. Disrupting this pathway alters the microbiota and impairs plant growth in iron-limiting soil. Furthermore, the microbiota improves iron-limiting plant performance via a mechanism dependent on plant iron import and secretion of the coumarin fraxetin. This beneficial trait is strain specific yet functionally redundant across phylogenetic lineages of the microbiota. Transcriptomic and elemental analyses revealed that this interaction between commensals and coumarins promotes growth by relieving iron starvation. These results show that coumarins improve plant performance by eliciting microbe-assisted iron nutrition. We propose that the bacterial root microbiota, stimulated by secreted coumarins, is an integral mediator of plant adaptation to iron-limiting soils.

Correction to: A molecular perspective on starch metabolism in woody tissues.

The original article was corrected.

A molecular perspective on starch metabolism in woody tissues.

MAIN CONCLUSION: The elucidation of the molecular mechanisms of starch synthesis and mobilization in perennial woody tissues is of the utmost scientific and agricultural importance. Starch is the main carbohydrate reserve in plants and is fundamental in human nutrition and several industrial processes. In leaves, starch accumulated during the day is degraded throughout the night and the resulting sugars, glucose and maltose, are exported to the cytosol by the specialized transmembrane translocators pGT and MEX, respectively. Nevertheless, the degradation of the starch granule is a complex process not completely elucidated. While the mechanisms of starch mobilization during germination in the dead endosperm of cereal seeds are well described, the molecular and biochemical mechanisms involved in starch storage in the heterotrophic tissues of woody plants and its utilization in spring and winter are still puzzling. It is known that some biochemical steps of starch synthesis are conserved in heterotrophic tissues and in the leaves, but some aspects are particular to sink organs. From an agronomic standpoint, the knowledge on starch storage and mobilization in woody tissues is pivotal to understand (and to optimize) some common practices in the field that modify source-sink relationships, such as pruning and defoliation. Soluble sugars resulting from starch are also pivotal to cold adaptation, and in several fruits, such as banana and kiwifruit, starch may provide soluble sugars during ripening. In this review, we explore the recent advances on the molecular mechanisms and regulations involved in starch synthesis and mobilization, with a focus on perennial woody tissues.

The association between burning mouth syndrome and sleep disturbance: A case-control multicentre study.

OBJECTIVES: To investigate the quality of sleep and the psychological profiles of a large cohort of Italian patients with burning mouth syndrome (BMS) and to clarify the relationships between these variables and pain. METHODS: In this case-control study, 200 patients with BMS vs an equal number of age- and sex-matched healthy controls, recruited in 10 universities, were enrolled. The Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), Numeric Pain Intensity Scale (NRS) and Total Pain Rating Index (T-PRI) were administered. Descriptive statistics, including the Mann-Whitney U test and hierarchical multiple linear regression analysis, were used. RESULTS: Poor sleep quality (PSQI ≥ 5) was present in 78.8% (160) patients with BMS. BMS patients had statistically higher scores in all items of the PSQI and ESS than the healthy controls (p < .001). A depressed mood and anxiety correlated positively with sleep disturbance. The Pearson correlations were 0.570 for the PSQI vs HAM-D (p < .001) and 0.549 for the PSQI vs HAM-A (p < .001). Pain intensity (NRS) poorly correlated to sleep quality; the Pearson correlation was 0.162 for the PSQI vs NRS (p = .021). CONCLUSIONS: The BMS patients showed a poor sleep quality, anxiety and depression, as compared with the controls, highlighting the relationships between oral burning, sleep and mood.

Monitoring of compositional changes during berry ripening in grape seed extracts of cv. Sangiovese (Vitis vinifera L.).

BACKGROUND: Seed oil and flours have been attracting the interest of researchers and industry, since they contain various bioactive components. We monitored the effects of ripening on lipids, monomeric flavan-3-ols, proanthocyanidins and tocols concentration in seed extracts from organically cultivated cv. Sangiovese vines. RESULTS: Linoleic acid was the most abundant fatty acid, followed by oleic, palmitic and stearic acids. The tocols detected were α-tocopherol, α-tocotrienol and γ-tocotrienol. The proanthocyanidins degree of polymerisation ranged from dimers to dodecamers; moreover, monomeric flavan-3-ols and polymeric proanthocyanidins were detected. Total flavan-3-ols (monomers, oligomers and polymers) concentration in grape seeds decreased during ripening. CONCLUSIONS: Fatty acids reached the highest level in post-veraison. The concentration of these compounds varied considerably during ripening. Capric acid has been found for the first time in grape seeds. α-Tocopherol and γ-tocotrienol decreased during ripening, while α-tocotrienol increased. The HPLC analysis with fluorimetric detection, conducted for the first time on cv. Sangiovese, revealed that the concentration of flavan-3-ols monomers, oligomeric proanthocyanidins and polymers greatly changed during ripening. These results suggest that the timing of bunch harvest plays a crucial role in the valorisation of grape seed flour. © 2016 Society of Chemical Industry.

Physiological responses in roots of the grapevine rootstock 140 Ruggeri subjected to Fe deficiency and Fe-heme nutrition.

Iron (Fe)-heme containing fertilizers can effectively prevent Fe deficiency. This paper aims to investigate root physiological responses after a short period of Fe-heme nutrition and Fe deficiency under two pH conditions (with or without HEPES) in the Fe chlorosis-tolerant grapevine rootstock 140 Ruggeri. Organic acids in root exudates, Fe reduction capacity, both roots and root exudates contributions, together with other physiological parameters associated to plant Fe status were evaluated in plants grown in hydroponics. Analyses of root tips by SEM, and Raman and IR spectra of the precipitates of Fe-heme fertilizers were performed. The physiological responses adopted by the tolerant 140 Ruggeri to the application of Fe-heme indicated an increased Fe reduction capacity of the roots. This is the first report showing oxalic, tartaric, malic and ascorbic as major organic acids in Vitis spp. root exudates. Plants reacted to Fe deficiency condition exuding a higher amount of ascorbic acid in the rhizosphere. The presence of HEPES in the medium favoured the malic acid exudation. The lowest concentration of oxalic acid was found in exudates of plants subjected to Fe-heme and could be associated to a higher accumulation in their root tips visualized by SEM analysis.

Sleep disturbances, anxiety and depression in patients with oral lichen planus: a case-control study.

BACKGROUND: The psychological factors and their association with chronic inflammatory disease, aren't well recognized, yet their importance in oral lichen planus is still debated. AIMS: The aim of this study was to investigate the prevalence of sleep disturbances, anxiety, depression and their association in patient with oral lichen planus. MATERIALS AND METHODS: 50 patients with oral lichen planus vs. equal number of age and sex-matched healthy controls were enrolled. Questionnaires examining insomnia symptoms, excessive daytime sleepiness (Pittsburgh sleep quality index and Epworth aleepiness scale) depression and anxiety (The Hamilton rating scale for Depression and Anxiety) were used. RESULTS: The patients with oral lichen planus had statistically higher scores in all items of the Pittsburgh sleep quality index, the Hamilton rating scale for depression and anxiety and Epworth sleepiness scale than the healthy controls. The median and inter-quartile range of the Pittsburgh sleep quality index was 5-2 and for the oral lichen planus patients and 4-2 for the healthy controls (P < 0.011). In the study group, a depressed mood and anxiety correlated positively with sleep disturbances. The Pearson correlations were 0.76 for Pittsburgh sleep quality Index vs. Hamilton rating scale for depression (P < 0.001) and 0.77 for Pittsburgh sleep quality Index vs. Hamilton rating scale for anxiety (P < 0.001). DISCUSSION: Oral lichen planus patients report a greater degree of sleep problems, depressed mood and anxiety as compared with controls. CONCLUSION: We suggest to screen sleep disturbances in patients with oral lichen planus because they could be considered a prodromal symptoms of mood disorders.

Mucosal leishmaniasis with primary oral involvement: a case series and a review of the literature.

OBJECTIVE: To analyze retrospectively a case series of primary oral leishmaniasis and to review the literature on head-neck primary mucosal leishmaniasis (ML) in immunocompetent patients. SUBJECTS AND METHODS: A PUBMED search was carried out from 1950 to 2013. Clinical records of patients with primary head-neck mucosal manifestations of leishmaniasis were analyzed. In addition, clinical records between 2001 and 2012 of patients with primary oral manifestations were collected in two independent hospitals. RESULTS: Our multicenter case series revealed seven patients with oral leishmaniasis. The most commonly affected site was the tongue (four patients, 57%), and the most common clinical presentation was an exophytic lesion (six patients, 85%). The literature review showed 11 reports published between 2005 and 2013, describing 13 patients (100% male) affected by head-neck primary ML (54% laryngeal, 31% oral, 23% pharyngeal, and 15% endonasal). The most common clinical presentation was an exophytic lesion (69%). CONCLUSIONS: The literature analysis revealed that in immunocompetent patients, the oral mucosa is the second most frequently affected site of the head and neck region. In the oral cavity, the tongue is the most affected site. Diagnosis of oral leishmaniasis represents a challenge but must be considered in any differential diagnosis of exophytic lesions of oral mucosa.

A multicenter phase II study of pazopanib in patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib.

BACKGROUND: Advanced GISTs are incurable, but often treatable for years with tyrosine kinase inhibitors (TKIs). The majority of GISTs harbor an oncogenic activating mutation in KIT or PDGFRA. Inhibition of this activating mutation with TKIs most often leads to durable disease control for many patients. However, almost all patients develop resistance to these TKIs, typically due to the development of secondary mutations, heralding the need for new therapeutic options. We conducted a phase II study evaluating the efficacy and toxicity of pazopanib, a broad spectrum TKI inhibiting KIT, VEGFRs (-1, -2, and -3), and PDGFR (-α and-ß) in patients with advanced GIST following failure of at least imatinib and sunitinib. METHODS: Patients received pazopanib 800 mg orally once daily. All patients were assessed for efficacy with CT scans every 8 weeks (two cycles). Patients continued pazopanib until progression or unacceptable toxicity. The primary end point was the 24-week nonprogression [complete response+partial response+stable disease (SD)] rate (NPR) per RECIST 1.1. Secondary end points included PFS, OS, and toxicity. RESULTS: Between August 2011 and September 2012, a total of 25 patients were treated at two institutions. Median number of prior therapy was 3 (range 2-7). A total of 90 cycles of pazopanib were administered, with a median of two cycles (range 1 to 17+) per patient. Best response of SD at any time was observed in 12 (48%) patients. The NPR was 17% [95% confidence interval (CI) 4.5-37]. All but one patient discontinued protocol either due to PD (n = 19) or intolerance (n = 4). One patient with succinate dehydrogenase (SDH)-deficient GIST exhibited continuing disease control after 17 cycles. The median PFS for the entire cohort was 1.9 months (95% CI 1.6-5.2), and the median OS was 10.7 months (95% CI 3.9-NR). CONCLUSIONS: Pazopanib was reasonably well tolerated with no unexpected toxicities. Pazopanib as a single agent has marginal activity in unselected heavily pretreated patients with advanced GIST.

Oral Syphilis: a retrospective analysis of 12 cases and a review of the literature.

OBJECTIVE: To present a retrospective analysis of multicentre case series of oral syphilis and a review of relevant literature. SUBJECTS AND METHODS: A PUBMED search was carried out from 1950 to 2011. Clinical records of patients with exclusive/prevalent oral manifestations of syphilis were collected and examined in three independent hospitals. RESULTS: Of 23 reports describing 34 patients were detected through the review (35% primary, 56% secondary, and 9% tertiary disease), describing unspecific ulcers (59%), mucosal patches (23%), keratosis (6%), pseudomembranes (3%), and gumma (9%). Multicentre case series revealed 12 patients with oral syphilis, of which 17%, 58%, and 25% with, respectively, primary, secondary, and tertiary lesions. Clinically, patients showed white patches (17%), blistering mucositis (8%), chronic unspecific ulcers with/without skin lesions (50%), gumma (17%), and necrosis of the dorsum of the tongue (8%). Oral bullae and tongue necrosis are never described in the current review. CONCLUSIONS: Diagnosis of syphilis remains a challenge because of the multiform and polymorphous clinical pattern at onset and its ability to imitate different diseases. It is mandatory to include syphilis in the differential diagnosis of unusual oral lesions. Diagnosis of oral lesions of syphilis is often difficult, and biopsy is required in controversial cases.

Phase II study of the HSP90-inhibitor BIIB021 in gastrointestinal stromal tumors.

BACKGROUND: HSP90 inhibition leads to proteosomal degradation of activated KIT and has in vitro activity against gastrointestinal stromal tumors (GIST). BIIB021 is an oral non-ansamycin HSP90 inhibitor. We carried out a phase II study of BIIB021 in patients with GIST refractory to imatinib and sunitinib. PATIENTS AND METHODS: The primary end-point was metabolic partial response (mPR) as assessed by fluorodeoxyglucose positron emission tomography (FDG-PET). The secondary end-points were pharmacokinetic assessments of BIIB021 and pharmacodynamic assessments of HSP70. Twenty-three patients were treated on two schedules: 12 pts received 600 mg twice a week (BIW) and 11 patients received 400 mg three times a week (TIW). All had prior imatinib and sunitinib but stopped>14 days before starting BIIB021. RESULTS: The median age was 59 years (33-88 years), 61% male, 44% Eastern Cooperative Oncology Group 1 (ECOG1). The best response was PR by FDG-PET for five patients (3/12 at 600 mg BIW and 2/9 at 400 TIW) for an overall response rate of 22%. The response duration was 25-138 days. Adverse events (AEs) were mild to moderate. The mean Cmax was 1.5 µmol and the mean AUC was 2.9 µmol h. Cmax>1.5 µmol was associated with a decrease in standardized uptake value (SUVmax). HSP70 increased substantially following treatment. CONCLUSIONS: This study met its primary end-point. BIIB021 leads to objective responses in refractory GIST patients. Pharmacodynamic studies confirmed HSP90 inhibition. Further evaluation of BIIB021 in GIST is warranted.

Adjuvant triamcinolone acetonide injections in oro-pharyngeal pemphigus vulgaris.

BACKGROUND: High-potency topical and perilesional/intralesional corticosteroids are becoming increasingly useful as adjuvant to treat autoimmune blistering diseases. OBJECTIVE: We sought to evaluate the role of perilesional/intralesional triamcinolone acetonide (PITA) injections in reducing the time for first complete clinical remission and the total amount of systemic corticosteroids in oro-pharyngeal pemphigus vulgaris (OPV) patients, and also the compliance of PITA injections, in terms of satisfaction, pain and discomfort. METHODS: Thirty-five OPV patients were treated with conventional immunosuppressive therapy (CIST) and received high potency topical corticosteroids (clobetasol and/or methylprednisolone) and/or PITA injections. Patients were grouped as follows: (i) a group of 16 patients was treated with PITA injections and (ii) a group of 19 patients without PITA injections. RESULTS: Sixteen patients treated with PITA injections and 19 without PITA injections reached complete clinical remission within 126.6 days (SD: 41; 95% CI: 104.7-148.8) and 153.2 days (SD: 97.4; 95% CI: 106.2-200.1) (P = 0.4) respectively. The total amount of corticosteroids in patients treated with PITA and without PITA was 4894 mg (SD: 2832; 95% CI: 3385-6403) and 5312 mg (SD: 4009; 95% CI: 3380-7245) (P = 0.4) respectively. Patients treated with PITA reported a satisfaction score significantly higher than pain (P = 0.0007) and discomfort score (P = 0.0006). CONCLUSION: Perilesional/intralesional triamcinolone acetonide injections seems to represent a helpful clinical tool to successfully join CIST, in terms of shortening the time of complete clinical remission, reducing the total amount of corticosteroids and obtaining an acceptable compliance.

Low mean level sustained and intermittent grip exertions: influence of age on fatigue and recovery.

The goal of this study was to quantify localised muscle fatigue resulting from low mean levels of exertion in younger (< 40 years) and older (> 50 years) adults. Fatigue, elicited in the finger flexor muscles by intermittent (10% mean maximum voluntary contraction (MVC)) and sustained (8% MVC) handgrip exercises, was quantified by a muscle twitch force response before, immediately after and during 3 h following exercise. Despite greater mean loads, recovery time was shorter following intermittent than sustained contractions, which suggests that recovery from fatigue is more sensitive to rest within the work cycle than mean work. The more pronounced effects for younger than older individuals following the sustained exertion indicate that changes in muscle fibre type composition might predispose older individuals to be more resistant to fatigue resulting from sustained contractions of low level. Performing hand exertion tasks requiring low mean force levels contributes to similar long-lasting fatigue effects regardless of gender and age. Intermittent periods of complete rest reduce muscle fatigue. Since fatigue was not perceived during recovery from the tested sustained and intermittent contractions, subjective evaluations may not be a reliable indicator of localised muscle fatigue.

Analysis of thromboembolic risk related to high-dose intravenous immunoglobulin treatment: a preliminary clinical study of 10 patients with autoimmune mucocutaneous blistering diseases.

BACKGROUND: Intravenous immunoglobulin (IVIg) treatment is a well-known treatment that has been used successfully in a broad spectrum of autoimmune diseases. Currently no data are available in the literature about the role of IVIg in the pathogenesis of thromboembolic events in patients with autoimmune blistering diseases refractory to conventional immunosuppressive treatment. AIM: To determine the relationship between IVIg and thromboembolism in patients with autoimmune blistering diseases and to establish a protocol to deal with the thromboembolic risk. METHODS: In our preliminary clinical study, 10 patients with autoimmune blistering diseases underwent IVIg cycles to a total of 133 cycles in all (total number of infusions in the patient group: 399), at a standard dose of 2 g/kg/infusion accompanied by an accurate and a complete clinical and laboratory screening for thromboembolism. Preventive measures, such as hydration before and after IVIg, and administration of 100 mg of acetyl salicylic acid (aspirin) or 1000 IU of subcutaneous heparin calcium per day for 3 weeks, were introduced to reduce the thromboembolic risk. RESULTS: Throughout the 2 years of IVIg treatment, no patient developed a superficial and/or deep venous or arterial thrombosis, even though some of the patients had underlying thromboembolic risk factors and had tested positive for some congenital and acquired thrombophilia markers. CONCLUSIONS: Our results indicate that thromboembolic events are uncommon, despite the presence of risk factors. However, as these disorders are very rare and the percentage of nonresponder patients is very low, further investigations are needed to better understand whether IVIg alone is able to trigger these fatal events in blistering disorders.

Brote de encefalitis de St. Louis en la provincia de Córdoba

La encefalitis de Saint Louis (ESL) es una enfermedad viral transmitida al humano por mosquitos del género culex spp. El agente causal es un arbovirus miembro de la familia flaviviridae. En Argentina es una infección de distribución amplia con una prevalencia serológica del 10-68%. Está demostrada su circulación en aves. Entre los meses de enero y abril de 2005 se presentaron en la provincia de Córdoba 48 casos de ESL. En nuestra experiencia asistimos 9 casos de esta encefalitis.